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  • Articles  (317)
  • Disease Models, Animal
  • Pregnancy
  • 2010-2014  (109)
  • 1980-1984  (208)
  • 1950-1954
  • Science. 207(4426): 78-80.  (1)
  • Science. 207(4427): 205-7.  (1)
  • Science. 207(4428): 315-7.  (1)
  • Science. 207(4428): 328-9.  (1)
  • Science. 207(4432): 788-91.  (1)
  • Science. 207(4433): 837-42.  (1)
  • Science. 207(4433): 902-4.  (1)
  • Science. 207(4434): 1008.  (1)
  • Science. 207(4435): 1079-80.  (1)
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  • Science. 207(4436): 1220-2.  (1)
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  • 25
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  • Articles  (317)
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  • 1
    Publication Date: 2010-05-15
    Description: Mycobacterium tuberculosis has a penetrance of its host population that would be the envy of most human pathogens. About one-third of the human population would have a positive skin test for the infection and is thus thought to harbor the bacterium. Globally, 22 "high-burden" countries account for more than 80% of the active tuberculosis cases in the world, which shows the inequitable distribution of the disease. There is no effective vaccine against infection, and current drug therapies are fraught with problems, predominantly because of the protracted nature of the treatment and the increasing occurrence of drug resistance. Here we focus on the biology of the host-pathogen interaction and discuss new and evolving strategies for intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872107/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872107/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, David G -- Barry, Clifton E 3rd -- Flynn, JoAnne L -- AI057086/AI/NIAID NIH HHS/ -- AI067027/AI/NIAID NIH HHS/ -- AI080651/AI/NIAID NIH HHS/ -- AI50732/AI/NIAID NIH HHS/ -- HL055936/HL/NHLBI NIH HHS/ -- HL075845/HL/NHLBI NIH HHS/ -- HL092883/HL/NHLBI NIH HHS/ -- HL100928/HL/NHLBI NIH HHS/ -- HL71241/HL/NHLBI NIH HHS/ -- R01 AI037859/AI/NIAID NIH HHS/ -- R01 AI050732/AI/NIAID NIH HHS/ -- R01 AI050732-07/AI/NIAID NIH HHS/ -- R01 AI057086/AI/NIAID NIH HHS/ -- R01 AI057086-06A2/AI/NIAID NIH HHS/ -- R01 AI067027/AI/NIAID NIH HHS/ -- R01 AI067027-05/AI/NIAID NIH HHS/ -- R01 AI080651/AI/NIAID NIH HHS/ -- R01 AI080651-02/AI/NIAID NIH HHS/ -- R01 HL055936/HL/NHLBI NIH HHS/ -- R01 HL055936-14/HL/NHLBI NIH HHS/ -- R01 HL075845/HL/NHLBI NIH HHS/ -- R01 HL075845-05/HL/NHLBI NIH HHS/ -- R01 HL100928/HL/NHLBI NIH HHS/ -- R01 HL100928-01/HL/NHLBI NIH HHS/ -- R33 HL092883/HL/NHLBI NIH HHS/ -- R33 HL092883-02/HL/NHLBI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 May 14;328(5980):852-6. doi: 10.1126/science.1184784.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. dgr8@cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466922" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antitubercular Agents/pharmacology/therapeutic use ; *BCG Vaccine/administration & dosage/immunology ; Biomarkers ; Disease Models, Animal ; Drug Discovery ; Drug Therapy, Combination ; Host-Pathogen Interactions ; Humans ; Mice ; *Mycobacterium tuberculosis/growth & development/immunology/metabolism ; Public Health Practice ; *Tuberculosis/drug therapy/immunology/microbiology/prevention & control ; Vaccination
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-06-26
    Description: Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasanetz, Fernando -- Deroche-Gamonet, Veronique -- Berson, Nadege -- Balado, Eric -- Lafourcade, Mathieu -- Manzoni, Olivier -- Piazza, Pier Vincenzo -- New York, N.Y. -- Science. 2010 Jun 25;328(5986):1709-12. doi: 10.1126/science.1187801.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM U862, NeuroCentre Magendie, 147 Rue Leo Saignat, 33077, Bordeaux Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576893" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Addictive ; Cocaine/administration & dosage ; Cocaine-Related Disorders/*physiopathology ; Disease Models, Animal ; Glutamic Acid/metabolism ; *Long-Term Synaptic Depression ; Nucleus Accumbens/*physiopathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Self Administration ; Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2010-06-26
    Description: Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Busskamp, Volker -- Duebel, Jens -- Balya, David -- Fradot, Mathias -- Viney, Tim James -- Siegert, Sandra -- Groner, Anna C -- Cabuy, Erik -- Forster, Valerie -- Seeliger, Mathias -- Biel, Martin -- Humphries, Peter -- Paques, Michel -- Mohand-Said, Saddek -- Trono, Didier -- Deisseroth, Karl -- Sahel, Jose A -- Picaud, Serge -- Roska, Botond -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):413-7. doi: 10.1126/science.1190897. Epub 2010 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576849" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dependovirus/genetics ; Disease Models, Animal ; Evoked Potentials, Visual ; *Genetic Therapy ; Genetic Vectors ; Halobacteriaceae/genetics ; Halorhodopsins/*genetics/*metabolism ; Humans ; Light ; Mice ; Mice, Knockout ; Promoter Regions, Genetic ; Retina/physiology ; Retinal Cone Photoreceptor Cells/*physiology ; Retinal Ganglion Cells/physiology ; Retinitis Pigmentosa/physiopathology/*therapy ; Tissue Culture Techniques ; Transfection ; Vision, Ocular ; Visual Pathways/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hengel, Hartmut -- Koszinowski, Ulrich H -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):51-2. doi: 10.1126/science.1188578.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Virology, Heinrich-Heine-University, Dusseldorf, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360096" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; Cytomegalovirus/genetics/immunology/*physiology ; Cytomegalovirus Infections/*immunology/*virology ; Cytomegalovirus Vaccines/*immunology ; Disease Models, Animal ; Genes, Viral ; Histocompatibility Antigens Class I/immunology ; Humans ; *Immune Evasion ; Macaca mulatta ; Superinfection ; Virus Shedding
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  • 5
    Publication Date: 2010-06-05
    Description: In the classical form of alpha1-antitrypsin (AT) deficiency, a point mutation in AT alters the folding of a liver-derived secretory glycoprotein and renders it aggregation-prone. In addition to decreased serum concentrations of AT, the disorder is characterized by accumulation of the mutant alpha1-antitrypsin Z (ATZ) variant inside cells, causing hepatic fibrosis and/or carcinogenesis by a gain-of-toxic function mechanism. The proteasomal and autophagic pathways are known to mediate degradation of ATZ. Here we show that the autophagy-enhancing drug carbamazepine (CBZ) decreased the hepatic load of ATZ and hepatic fibrosis in a mouse model of AT deficiency-associated liver disease. These results provide a basis for testing CBZ, which has an extensive clinical safety profile, in patients with AT deficiency and also provide a proof of principle for therapeutic use of autophagy enhancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hidvegi, Tunda -- Ewing, Michael -- Hale, Pamela -- Dippold, Christine -- Beckett, Caroline -- Kemp, Carolyn -- Maurice, Nicholas -- Mukherjee, Amitava -- Goldbach, Christina -- Watkins, Simon -- Michalopoulos, George -- Perlmutter, David H -- DK076918/DK/NIDDK NIH HHS/ -- HL037784/HL/NHLBI NIH HHS/ -- R01 DK076918/DK/NIDDK NIH HHS/ -- R01 DK084512/DK/NIDDK NIH HHS/ -- RR022241/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):229-32. doi: 10.1126/science.1190354. Epub 2010 Jun 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20522742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/*drug effects ; Carbamazepine/administration & dosage/*pharmacology/therapeutic use ; Cell Line ; Disease Models, Animal ; Endoplasmic Reticulum/metabolism ; HeLa Cells ; Humans ; Liver/drug effects/*metabolism/pathology ; Liver Cirrhosis/*drug therapy/etiology/metabolism/pathology ; Mice ; Mice, Transgenic ; Mutant Proteins/chemistry/metabolism ; Phagosomes/drug effects/ultrastructure ; Phenotype ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Solubility ; alpha 1-Antitrypsin/chemistry/genetics/*metabolism ; alpha 1-Antitrypsin Deficiency/complications/*metabolism/pathology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2010-07-21
    Description: The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence 〉 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence 〈 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001187/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abdool Karim, Quarraisha -- Abdool Karim, Salim S -- Frohlich, Janet A -- Grobler, Anneke C -- Baxter, Cheryl -- Mansoor, Leila E -- Kharsany, Ayesha B M -- Sibeko, Sengeziwe -- Mlisana, Koleka P -- Omar, Zaheen -- Gengiah, Tanuja N -- Maarschalk, Silvia -- Arulappan, Natasha -- Mlotshwa, Mukelisiwe -- Morris, Lynn -- Taylor, Douglas -- CAPRISA 004 Trial Group -- AI51794/AI/NIAID NIH HHS/ -- D43 TW000231/TW/FIC NIH HHS/ -- D43 TW000231-17/TW/FIC NIH HHS/ -- D43TW00231/TW/FIC NIH HHS/ -- U01 AI068619/AI/NIAID NIH HHS/ -- U01AI068633/AI/NIAID NIH HHS/ -- U01AI46749/AI/NIAID NIH HHS/ -- U19 AI051794/AI/NIAID NIH HHS/ -- U19 AI051794-05/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for the AIDS Program of Research in South Africa (CAPRISA), Durban 4013, South Africa. caprisa@ukzn.ac.za〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20643915" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/administration & dosage/adverse effects/*analogs & ; derivatives/therapeutic use ; Administration, Intravaginal ; Adolescent ; Adult ; Anti-HIV Agents/*administration & dosage/adverse effects/therapeutic use ; Anti-Infective Agents, Local/administration & dosage/adverse effects/therapeutic ; use ; Double-Blind Method ; Drug Resistance, Viral ; Female ; HIV Infections/epidemiology/*prevention & control ; HIV-1/*drug effects/physiology ; Humans ; Incidence ; Organophosphonates/*administration & dosage/adverse effects/therapeutic use ; Patient Compliance ; Pregnancy ; Pregnancy Outcome ; Rural Population/statistics & numerical data ; Sexual Behavior ; South Africa/epidemiology ; Tenofovir ; Urban Population/statistics & numerical data ; Vaginal Creams, Foams, and Jellies ; Viral Load ; Young Adult
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  • 7
    Publication Date: 2011-01-06
    Description: Model organisms such as the fruit fly Drosophila melanogaster can help to elucidate the molecular basis of complex diseases such as cancer. Mutations in the Drosophila gene lethal (3) malignant brain tumor cause malignant growth in the larval brain. Here we show that l(3)mbt tumors exhibited a soma-to-germline transformation through the ectopic expression of genes normally required for germline stemness, fitness, or longevity. Orthologs of some of these genes were also expressed in human somatic tumors. In addition, inactivation of any of the germline genes nanos, vasa, piwi, or aubergine suppressed l(3)mbt malignant growth. Our results demonstrate that germline traits are necessary for tumor growth in this Drosophila model and suggest that inactivation of germline genes might have tumor-suppressing effects in other species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janic, Ana -- Mendizabal, Leire -- Llamazares, Salud -- Rossell, David -- Gonzalez, Cayetano -- New York, N.Y. -- Science. 2010 Dec 24;330(6012):1824-7. doi: 10.1126/science.1195481.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Division Group, Institute for Research in Biomedicine (IRB-Barcelona), PCB, c/Baldiri Reixac 10-12, Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21205669" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Brain/growth & development/metabolism ; Brain Neoplasms/*genetics/pathology ; *Cell Transformation, Neoplastic ; DEAD-box RNA Helicases/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Disease Models, Animal ; Drosophila Proteins/genetics/metabolism ; *Drosophila melanogaster/genetics/growth & development/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; *Genes, Insect ; Genes, Tumor Suppressor ; Germ Cells/*physiology ; Humans ; MicroRNAs/genetics/metabolism ; Models, Animal ; Neoplasm Transplantation ; Peptide Initiation Factors/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; RNA-Binding Proteins/genetics/metabolism ; RNA-Induced Silencing Complex/genetics/metabolism ; Transplantation, Homologous ; Up-Regulation
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-07-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Leslie -- New York, N.Y. -- Science. 2011 Jul 29;333(6042):540-3. doi: 10.1126/science.333.6042.540.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798924" target="_blank"〉PubMed〈/a〉
    Keywords: Birth Rate ; Female ; Forecasting ; Humans ; Male ; Parity ; *Population Growth ; Pregnancy
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  • 9
    Publication Date: 2011-04-16
    Description: Transforming growth factor-beta (TGFbeta) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFbeta can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal-regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFbeta. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase-1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFbeta signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111087/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holm, Tammy M -- Habashi, Jennifer P -- Doyle, Jefferson J -- Bedja, Djahida -- Chen, YiChun -- van Erp, Christel -- Lindsay, Mark E -- Kim, David -- Schoenhoff, Florian -- Cohn, Ronald D -- Loeys, Bart L -- Thomas, Craig J -- Patnaik, Samarjit -- Marugan, Juan J -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-12/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):358-61. doi: 10.1126/science.1192149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493862" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthracenes/pharmacology/therapeutic use ; Aorta/pathology ; Aortic Aneurysm/*metabolism/pathology/physiopathology/prevention & control ; Diphenylamine/analogs & derivatives/pharmacology/therapeutic use ; Disease Models, Animal ; Disease Progression ; Enzyme Activation ; Losartan/pharmacology/therapeutic use ; *MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism ; Mitogen-Activated Protein Kinase 8/antagonists & inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Smad2 Protein/metabolism ; Smad4 Protein/deficiency/genetics ; Sulfonamides/pharmacology/therapeutic use ; Transforming Growth Factor beta/antagonists & inhibitors/immunology/*metabolism
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  • 10
    Publication Date: 2011-11-05
    Description: Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by expansion of a translated CAG repeat in Ataxin-1 (ATXN1). To determine the long-term effects of exercise, we implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by up-regulation of epidermal growth factor and consequential down-regulation of Capicua, which is an ATXN1 interactor. Offspring of Capicua mutant mice bred to SCA1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reduction of Capicua levels--either genetically or by exercise--mitigated the disease phenotypes by dampening the toxic gain of function. Thus, exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232424/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232424/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fryer, John D -- Yu, Peng -- Kang, Hyojin -- Mandel-Brehm, Caleigh -- Carter, Angela N -- Crespo-Barreto, Juan -- Gao, Yan -- Flora, Adriano -- Shaw, Chad -- Orr, Harry T -- Zoghbi, Huda Y -- 1F32NS055545/NS/NINDS NIH HHS/ -- HD24064/HD/NICHD NIH HHS/ -- NS022920/NS/NINDS NIH HHS/ -- NS045667/NS/NINDS NIH HHS/ -- NS27699/NS/NINDS NIH HHS/ -- NS27699-20S1/NS/NINDS NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- P30 HD024064-22/HD/NICHD NIH HHS/ -- P30 HD024064-23/HD/NICHD NIH HHS/ -- R01 NS027699/NS/NINDS NIH HHS/ -- R01 NS027699-20S1/NS/NINDS NIH HHS/ -- R01 NS027699-21/NS/NINDS NIH HHS/ -- R01 NS027699-22/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Nov 4;334(6056):690-3. doi: 10.1126/science.1212673.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22053053" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ataxin-1 ; Ataxins ; Cerebellum/metabolism ; Disease Models, Animal ; *Exercise Therapy ; Gene Knock-In Techniques ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Repressor Proteins/genetics/*physiology ; Spinocerebellar Ataxias/genetics/*therapy
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 11
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funder, John W -- New York, N.Y. -- Science. 2011 Feb 11;331(6018):685-6. doi: 10.1126/science.1202887.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Victoria 3168, Australia. john.funder@princehenrys.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21310991" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Cortex Neoplasms/*genetics/physiopathology ; Adrenal Glands/pathology ; Adrenocortical Adenoma/*genetics/physiopathology ; Aldosterone/*metabolism ; Animals ; Disease Models, Animal ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/*genetics/metabolism ; Humans ; Hyperaldosteronism/*genetics/physiopathology ; Hyperplasia ; Hypertension/physiopathology ; Male ; Mice ; Mutation
    Print ISSN: 0036-8075
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  • 12
    Publication Date: 2011-10-15
    Description: To establish chronic infections, viruses must develop strategies to evade the host's immune responses. Many retroviruses, including mouse mammary tumor virus (MMTV), are transmitted most efficiently through mucosal surfaces rich in microbiota. We found that MMTV, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. This process required the intestinal microbiota, as antibiotic-treated mice or germ-free mice did not transmit infectious virus to their offspring. MMTV-bound bacterial lipopolysaccharide triggered Toll-like receptor 4 and subsequent interleukin-6 (IL-6)-dependent induction of the inhibitory cytokine IL-10. Thus, MMTV has evolved to rely on the interaction with the microbiota to induce an immune evasion pathway. Together, these findings reveal the fundamental importance of commensal microbiota in viral infections.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519937/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kane, Melissa -- Case, Laure K -- Kopaskie, Karyl -- Kozlova, Alena -- MacDearmid, Cameron -- Chervonsky, Alexander V -- Golovkina, Tatyana V -- AI082418/AI/NIAID NIH HHS/ -- AI090084/AI/NIAID NIH HHS/ -- CA100383/CA/NCI NIH HHS/ -- DK42086/DK/NIDDK NIH HHS/ -- P30 CA014599/CA/NCI NIH HHS/ -- R01 AI090084/AI/NIAID NIH HHS/ -- R01 CA134667/CA/NCI NIH HHS/ -- R56 AI090084/AI/NIAID NIH HHS/ -- T32 AI065382-01/AI/NIAID NIH HHS/ -- T32GM007183/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Oct 14;334(6053):245-9. doi: 10.1126/science.1210718.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21998394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Anti-Bacterial Agents/pharmacology ; Antibodies, Viral/biosynthesis ; Antigens, Viral/immunology ; *Bacterial Physiological Phenomena ; Female ; Germ-Free Life ; *Immune Evasion ; Interleukin-10/genetics/metabolism ; Intestinal Mucosa/*virology ; Intestines/*microbiology ; Lipopolysaccharides/immunology/metabolism ; Mammary Tumor Virus, Mouse/*immunology/*pathogenicity ; *Metagenome ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Pregnancy ; Pregnancy Complications, Infectious/virology ; Retroviridae Infections/immunology/*transmission/virology ; Specific Pathogen-Free Organisms ; Toll-Like Receptor 4/immunology/metabolism ; Tumor Virus Infections/immunology/transmission/virology ; Virus Replication
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  • 13
    Publication Date: 2011-08-13
    Description: Midbrain dopamine neurons regulate many important behavioral processes, and their dysfunctions are associated with several human neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD) and schizophrenia. Here, we report that these neurons in mice selectively express guanylyl cyclase-C (GC-C), a membrane receptor previously thought to be expressed mainly in the intestine. GC-C activation potentiates the excitatory responses mediated by glutamate and acetylcholine receptors via the activity of guanosine 3',5'-monophosphate-dependent protein kinase (PKG). Mice in which GC-C has been knocked out exhibit hyperactivity and attention deficits. Moreover, their behavioral phenotypes are reversed by ADHD therapeutics and a PKG activator. These results indicate important behavioral and physiological functions for the GC-C/PKG signaling pathway within the brain and suggest new therapeutic targets for neuropsychiatric disorders related to the malfunctions of midbrain dopamine neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Rong -- Ding, Cheng -- Hu, Ji -- Lu, Yao -- Liu, Fei -- Mann, Elizabeth -- Xu, Fuqiang -- Cohen, Mitchell B -- Luo, Minmin -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1642-6. doi: 10.1126/science.1207675. Epub 2011 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21835979" target="_blank"〉PubMed〈/a〉
    Keywords: Amphetamine/administration & dosage ; Animals ; Attention ; Attention Deficit Disorder with Hyperactivity/genetics/*metabolism ; Behavior, Animal/drug effects ; Cyclic GMP/metabolism ; Cyclic GMP-Dependent Protein Kinases/*metabolism ; Disease Models, Animal ; Dopamine/metabolism ; Enzyme Activation ; Gastrointestinal Hormones/metabolism/pharmacology ; Glycine/analogs & derivatives/metabolism/pharmacology ; Impulsive Behavior ; Ligands ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects ; Natriuretic Peptides/metabolism/pharmacology ; Neurons/*metabolism ; Patch-Clamp Techniques ; Receptors, Glutamate/metabolism ; Receptors, Guanylate Cyclase-Coupled/genetics/*metabolism ; Receptors, Muscarinic/metabolism ; Receptors, Peptide/genetics/*metabolism ; Resorcinols/metabolism/pharmacology ; Signal Transduction ; Substantia Nigra/cytology/*metabolism ; Ventral Tegmental Area/cytology/*metabolism
    Print ISSN: 0036-8075
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  • 14
    Publication Date: 2011-10-29
    Description: Germline mutations of the breast cancer 1 (BRCA1) gene are a major cause of familial breast and ovarian cancer. The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression. To test this hypothesis, we generated mice that express an enzymatically defective Brca1. We found that this mutant Brca1 prevents tumor formation to the same degree as does wild-type Brca1 in three different genetically engineered mouse (GEM) models of cancer. In contrast, a mutation that ablates phosphoprotein recognition by the BRCA C terminus (BRCT) domains of BRCA1 elicits tumors in each of the three GEM models. Thus, BRCT phosphoprotein recognition, but not the E3 ligase activity, is required for BRCA1 tumor suppression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904783/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904783/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shakya, Reena -- Reid, Latarsha J -- Reczek, Colleen R -- Cole, Francesca -- Egli, Dieter -- Lin, Chyuan-Sheng -- deRooij, Dirk G -- Hirsch, Steffen -- Ravi, Kandasamy -- Hicks, James B -- Szabolcs, Matthias -- Jasin, Maria -- Baer, Richard -- Ludwig, Thomas -- F31-CA132626/CA/NCI NIH HHS/ -- F32-HD51392/HD/NICHD NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- P01-CA97403/CA/NCI NIH HHS/ -- R01 CA137023/CA/NCI NIH HHS/ -- R01 HD040916/HD/NICHD NIH HHS/ -- R01 HD040916-10/HD/NICHD NIH HHS/ -- R01-CA137023/CA/NCI NIH HHS/ -- R01-HD40916/HD/NICHD NIH HHS/ -- T32-CA09503/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Oct 28;334(6055):525-8. doi: 10.1126/science.1209909.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22034435" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/chemistry/*metabolism ; Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; Cells, Cultured ; Disease Models, Animal ; Embryonic Stem Cells/metabolism ; *Genes, BRCA1 ; Ligands ; Mammary Neoplasms, Experimental/*genetics/metabolism ; Mice ; Mutant Proteins/chemistry/genetics/metabolism ; Pancreatic Neoplasms/*genetics/metabolism ; Phosphoproteins/*metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; RING Finger Domains ; Tumor Suppressor Proteins/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 2011-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1569-71. doi: 10.1126/science.333.6049.1569.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21921174" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Animals ; Antineoplastic Agents/*therapeutic use ; Child ; Child, Preschool ; Clinical Trials as Topic ; Disease Models, Animal ; Gene Expression Profiling ; Humans ; Mice ; *Molecular Targeted Therapy ; Neuroblastoma/*drug therapy/*genetics ; *Precision Medicine
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-06-04
    Description: Rett syndrome (RTT) is a postnatal neurological disorder caused by mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2 (MeCP2). The onset of RTT symptoms during early life together with findings suggesting neurodevelopmental abnormalities in RTT and mouse models of RTT raised the question of whether maintaining MeCP2 function exclusively during early life might protect against disease. We show by using an inducible model of RTT that deletion of Mecp2 in adult mice recapitulates the germline knock-out phenotype, underscoring the ongoing role of MeCP2 in adult neurological function. Moreover, unlike the effects of other epigenetic instructions programmed during early life, the effects of early MeCP2 function are lost soon after its deletion. These findings suggest that therapies for RTT must be maintained throughout life.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150190/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150190/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGraw, Christopher M -- Samaco, Rodney C -- Zoghbi, Huda Y -- F31-NS073317/NS/NINDS NIH HHS/ -- HD024064/HD/NICHD NIH HHS/ -- NS057819/NS/NINDS NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- P30 HD024064-22/HD/NICHD NIH HHS/ -- R01 NS057819/NS/NINDS NIH HHS/ -- R01 NS057819-05/NS/NINDS NIH HHS/ -- T32-NS043124/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jul 8;333(6039):186. doi: 10.1126/science.1206593. Epub 2011 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21636743" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Disease Models, Animal ; Gene Expression Regulation ; Learning ; Male ; Memory ; Methyl-CpG-Binding Protein 2/genetics/*physiology ; Mice ; Mice, Knockout ; *Nervous System Physiological Phenomena ; Rett Syndrome/genetics/*physiopathology
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  • 17
    Publication Date: 2011-04-16
    Description: Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown. We show that loss of AT2 expression accelerates the aberrant growth and rupture of the aorta in a mouse model of Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm progression in the mice; full protection required intact AT2 signaling. The angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less effective. Both drugs attenuated canonical transforming growth factor-beta (TGFbeta) signaling in the aorta, but losartan uniquely inhibited TGFbeta-mediated activation of extracellular signal-regulated kinase (ERK), by allowing continued signaling through AT2. These data highlight the protective nature of AT2 signaling and potentially inform the choice of therapies in MFS and related disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097422/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Habashi, Jennifer P -- Doyle, Jefferson J -- Holm, Tammy M -- Aziz, Hamza -- Schoenhoff, Florian -- Bedja, Djahida -- Chen, YiChun -- Modiri, Alexandra N -- Judge, Daniel P -- Dietz, Harry C -- P01 AR049698/AR/NIAMS NIH HHS/ -- P01 AR049698-07/AR/NIAMS NIH HHS/ -- R01 AR041135/AR/NIAMS NIH HHS/ -- R01 AR041135-17/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):361-5. doi: 10.1126/science.1192152.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493863" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/metabolism ; Angiotensin II Type 1 Receptor Blockers/pharmacology/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/pharmacology/therapeutic use ; Animals ; Aorta ; Aortic Aneurysm/drug therapy/*metabolism/pathology/prevention & control ; Aortic Rupture/metabolism/pathology/prevention & control ; Disease Models, Animal ; Disease Progression ; Enalapril/pharmacology/therapeutic use ; Losartan/pharmacology/therapeutic use ; MAP Kinase Signaling System ; Marfan Syndrome/drug therapy/*metabolism/pathology ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/*antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinase 3/*antagonists & inhibitors/metabolism ; Receptor, Angiotensin, Type 2/genetics/*metabolism ; *Signal Transduction ; Transforming Growth Factor beta/metabolism
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-02-19
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775075/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775075/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hewitt, Sylvia C -- Korach, Kenneth S -- ZIA ES070065-35/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Feb 18;331(6019):863-4. doi: 10.1126/science.1202372.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, NC 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21330520" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics/*metabolism ; Cell Proliferation ; Embryo Implantation/*physiology ; Endometrium/cytology/*metabolism ; Epithelial Cells/cytology/physiology ; Estrogens/metabolism ; Female ; Fibroblast Growth Factors/*metabolism ; Gene Expression Profiling ; Mice ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; Progesterone/*metabolism ; RNA, Messenger/genetics/metabolism ; *Signal Transduction ; Stromal Cells/metabolism
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  • 19
    Publication Date: 2012-06-23
    Description: Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herfst, Sander -- Schrauwen, Eefje J A -- Linster, Martin -- Chutinimitkul, Salin -- de Wit, Emmie -- Munster, Vincent J -- Sorrell, Erin M -- Bestebroer, Theo M -- Burke, David F -- Smith, Derek J -- Rimmelzwaan, Guus F -- Osterhaus, Albert D M E -- Fouchier, Ron A M -- DP1-OD000490-01/OD/NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1534-41. doi: 10.1126/science.1213362.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723413" target="_blank"〉PubMed〈/a〉
    Keywords: Air Microbiology ; Amino Acid Substitution ; Animals ; Antiviral Agents/pharmacology ; Containment of Biohazards ; Disease Models, Animal ; Female ; *Ferrets ; Hemagglutinin Glycoproteins, Influenza ; Virus/chemistry/genetics/immunology/metabolism ; Humans ; Immune Sera ; Influenza A Virus, H5N1 Subtype/drug effects/*genetics/*pathogenicity/physiology ; Influenza in Birds/epidemiology/virology ; Influenza, Human/epidemiology/transmission/*virology ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Orthomyxoviridae Infections/transmission/*virology ; Oseltamivir/pharmacology ; Pandemics ; Poultry ; RNA Replicase/chemistry/genetics ; Reassortant Viruses/pathogenicity ; Receptors, Virus/metabolism ; Respiratory System/*virology ; Reverse Genetics ; Serial Passage ; Sialic Acids/metabolism ; Viral Proteins/chemistry/genetics ; Virulence ; Virus Replication ; Virus Shedding
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):286. doi: 10.1126/science.336.6079.286.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517832" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcysteine/*administration & dosage/therapeutic use ; Animals ; Animals, Newborn ; Astrocytes/drug effects ; Brain/*drug effects ; Cerebral Palsy/*drug therapy ; Dendrimers/*administration & dosage/therapeutic use ; Disease Models, Animal ; Microglia/drug effects ; Neuroprotective Agents/administration & dosage/therapeutic use ; Rabbits
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  • 21
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-03-01
    Description: Female rodents are known to terminate pregnancies after exposure to unfamiliar males ("Bruce effect"). Although laboratory support abounds, direct evidence for a Bruce effect under natural conditions is lacking. Here, we report a strong Bruce effect in a wild primate, the gelada (Theropithecus gelada). Female geladas terminate 80% of pregnancies in the weeks after a dominant male is replaced. Further, data on interbirth intervals suggest that pregnancy termination offers fitness benefits for females whose offspring would otherwise be susceptible to infanticide. Taken together, data support the hypothesis that the Bruce effect can be an adaptive strategy for females.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, Eila K -- Lu, Amy -- Bergman, Thore J -- Beehner, Jacinta C -- New York, N.Y. -- Science. 2012 Mar 9;335(6073):1222-5. doi: 10.1126/science.1213600. Epub 2012 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, University of Michigan, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22362878" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Wild ; *Behavior, Animal ; Birth Rate ; Estrogens/analysis ; Ethiopia ; Feces/chemistry ; Female ; *Genetic Fitness ; Gestational Age ; Male ; Pregnancy ; Pregnancy Outcome ; *Pregnancy, Animal ; Sexual Behavior, Animal ; Social Behavior ; *Social Dominance ; *Theropithecus/physiology/psychology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-06-23
    Description: Given the yearly challenge of seasonal influenza and the potential catastrophic consequences of future pandemics, the need for intensive basic and clinical influenza research is unquestionable. Although the fruits of decades of research have enabled dramatic improvements in our ability to prevent and treat influenza, many fundamental questions remain, including those related to the complex factors associated with host switching and transmission of influenza viruses. Recent public concern over two H5N1 influenza manuscripts that studied the transmissibility of influenza viruses has triggered intense discussion on dual-use research and the way forward.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fauci, Anthony S -- Collins, Francis S -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1522-3. doi: 10.1126/science.1224305.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institutes of Health, Bethesda, MD 20892, USA. afauci@niaid.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723407" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; Animals ; *Biomedical Research ; Bioterrorism ; Disease Models, Animal ; Evolution, Molecular ; Ferrets ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*pathogenicity ; Influenza, Human/mortality/transmission/*virology ; Mutation ; National Institutes of Health (U.S.) ; Orthomyxoviridae Infections/transmission/*virology ; Public Health ; Public Policy ; *Publishing ; Reassortant Viruses/genetics/pathogenicity ; Risk Assessment ; Security Measures ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chamberlain, Jeffrey S -- R37 AR040864/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 14;338(6113):1431-2. doi: 10.1126/science.1233074.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, School of Medicine, University of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195-7720, USA. Jsc5@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239725" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium Channel Blockers/administration & dosage/therapeutic use ; Clinical Trials as Topic ; Dantrolene/administration & dosage/*therapeutic use ; Disease Models, Animal ; Dystrophin/*biosynthesis/genetics ; Exons/genetics ; Mice ; Muscle Relaxants, Central/administration & dosage/*therapeutic use ; Muscular Dystrophy, Duchenne/genetics/*therapy ; Oligonucleotides, Antisense/administration & dosage/*therapeutic use ; RNA Precursors/genetics ; Ryanodine Receptor Calcium Release Channel/metabolism ; Sequence Deletion
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  • 24
    Publication Date: 2012-04-12
    Description: Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor beta subunit (CBFbeta), and induces chondrogenesis by regulating the CBFbeta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Kristen -- Zhu, Shoutian -- Tremblay, Matthew S -- Payette, Joshua N -- Wang, Jianing -- Bouchez, Laure C -- Meeusen, Shelly -- Althage, Alana -- Cho, Charles Y -- Wu, Xu -- Schultz, Peter G -- New York, N.Y. -- Science. 2012 May 11;336(6082):717-21. doi: 10.1126/science.1215157. Epub 2012 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. kjohnson@gnf.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491093" target="_blank"〉PubMed〈/a〉
    Keywords: Anilides/administration & dosage/chemistry/*pharmacology/therapeutic use ; Animals ; Cartilage, Articular/*cytology ; Cattle ; Cell Nucleus/metabolism ; Chondrocytes/cytology/*drug effects/metabolism/physiology ; *Chondrogenesis ; Contractile Proteins/metabolism ; Core Binding Factor Alpha 2 Subunit/metabolism ; Core Binding Factor beta Subunit/metabolism ; Disease Models, Animal ; Filamins ; High-Throughput Screening Assays ; Humans ; Mesenchymal Stromal Cells/cytology/*drug effects/physiology ; Mice ; Microfilament Proteins/metabolism ; Osteoarthritis/*drug therapy/pathology/physiopathology ; Phthalic Acids/administration & dosage/chemistry/*pharmacology/therapeutic use ; Regeneration ; Small Molecule Libraries ; Structure-Activity Relationship
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  • 25
    Publication Date: 2012-03-24
    Description: Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437652/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437652/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olszak, Torsten -- An, Dingding -- Zeissig, Sebastian -- Vera, Miguel Pinilla -- Richter, Julia -- Franke, Andre -- Glickman, Jonathan N -- Siebert, Reiner -- Baron, Rebecca M -- Kasper, Dennis L -- Blumberg, Richard S -- AI090102/AI/NIAID NIH HHS/ -- DK034854/DK/NIDDK NIH HHS/ -- DK44319/DK/NIDDK NIH HHS/ -- DK51362/DK/NIDDK NIH HHS/ -- DK53056/DK/NIDDK NIH HHS/ -- DK88199/DK/NIDDK NIH HHS/ -- P30 DK034854/DK/NIDDK NIH HHS/ -- R01 DK044319/DK/NIDDK NIH HHS/ -- R01 DK088199/DK/NIDDK NIH HHS/ -- R37 DK044319/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 Apr 27;336(6080):489-93. doi: 10.1126/science.1219328. Epub 2012 Mar 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22442383" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Animals, Newborn ; Antigens, CD1d/immunology ; Asthma/*immunology ; Bacteria/*growth & development ; Chemokine CXCL6/genetics/metabolism ; Colitis, Ulcerative/chemically induced/*immunology ; Colon/immunology/microbiology ; DNA Methylation ; Disease Models, Animal ; Disease Susceptibility ; Germ-Free Life ; Intestinal Mucosa/*immunology ; Intestines/immunology/*microbiology ; Lung/*immunology ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells/*immunology ; Oxazolone ; Receptors, CXCR/genetics/metabolism ; Specific Pathogen-Free Organisms
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  • 26
    Publication Date: 2012-02-11
    Description: Alzheimer's disease (AD) is associated with impaired clearance of beta-amyloid (Abeta) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Abeta within hours in an apoE-dependent manner. Abeta plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Abeta clearance mechanisms, resulting in the rapid reversal of a broad range of Abeta-induced deficits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651582/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651582/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cramer, Paige E -- Cirrito, John R -- Wesson, Daniel W -- Lee, C Y Daniel -- Karlo, J Colleen -- Zinn, Adriana E -- Casali, Brad T -- Restivo, Jessica L -- Goebel, Whitney D -- James, Michael J -- Brunden, Kurt R -- Wilson, Donald A -- Landreth, Gary E -- AG030482-03S1/AG/NIA NIH HHS/ -- DC003906/DC/NIDCD NIH HHS/ -- K01 AG029524/AG/NIA NIH HHS/ -- P50-AG005681/AG/NIA NIH HHS/ -- R01 AG030482/AG/NIA NIH HHS/ -- R01 AG037693/AG/NIA NIH HHS/ -- R01 DC003906/DC/NIDCD NIH HHS/ -- R01-AG037693/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 23;335(6075):1503-6. doi: 10.1126/science.1217697. Epub 2012 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323736" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*drug therapy/*metabolism ; Amyloid beta-Peptides/*metabolism ; Amyloidosis/drug therapy/metabolism ; Animals ; Apolipoproteins E/*metabolism ; Astrocytes/drug effects/metabolism ; Behavior, Animal/drug effects ; Brain/drug effects/*metabolism ; Disease Models, Animal ; Extracellular Fluid/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia/drug effects/metabolism ; Molecular Targeted Therapy ; Odors ; Olfactory Pathways/drug effects/physiology ; Orphan Nuclear Receptors/metabolism ; PPAR gamma/metabolism ; Phagocytosis ; Plaque, Amyloid/drug therapy ; Retinoid X Receptors/agonists/metabolism ; Tetrahydronaphthalenes/*pharmacology/*therapeutic use
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stern, Peter -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):67. doi: 10.1126/science.338.6103.67.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042883" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Depressive Disorder, Major/epidemiology/*pathology/*physiopathology ; Disease Models, Animal ; Humans ; Quality of Life
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  • 28
    Publication Date: 2013-04-27
    Description: Secondary bacterial pneumonia leads to increased morbidity and mortality from influenza virus infections. What causes this increased susceptibility, however, is not well defined. Host defense from infection relies not only on immune resistance mechanisms but also on the ability to tolerate a given level of pathogen burden. Failure of either resistance or tolerance can contribute to disease severity, making it hard to distinguish their relative contribution. We employ a coinfection mouse model of influenza virus and Legionella pneumophila in which we can separate resistance and tolerance. We demonstrate that influenza virus can promote susceptibility to lethal bacterial coinfection, even when bacterial infection is controlled by the immune system. We propose that this failure of host defense is due to impaired ability to tolerate tissue damage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933032/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jamieson, Amanda M -- Pasman, Lesley -- Yu, Shuang -- Gamradt, Pia -- Homer, Robert J -- Decker, Thomas -- Medzhitov, Ruslan -- AI R01 055502/AI/NIAID NIH HHS/ -- R01 046688/PHS HHS/ -- R01 AI046688/AI/NIAID NIH HHS/ -- R01 AI055502/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1230-4. doi: 10.1126/science.1233632. Epub 2013 Apr 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. amanda_jamieson@brown.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23618765" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspase 1 ; Coinfection/*immunology/pathology ; Disease Models, Animal ; Host-Pathogen Interactions/immunology ; Interleukin-1beta/metabolism ; *Legionella pneumophila ; Legionnaires' Disease/*immunology/pathology ; Lung/microbiology/pathology/virology ; Mice ; Mice, Inbred C57BL ; *Orthomyxoviridae ; Orthomyxoviridae Infections/*immunology/pathology ; Pneumonia, Bacterial/*immunology/pathology ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 3/metabolism ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/metabolism
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1436. doi: 10.1126/science.342.6165.1436-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357287" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Separation ; Cloning, Organism/*methods ; Female ; Humans ; *Induced Pluripotent Stem Cells ; Nuclear Transfer Techniques ; Pregnancy ; *Research Embryo Creation ; Surrogate Mothers
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  • 30
    Publication Date: 2013-11-30
    Description: Hypercholesterolemia is a risk factor for estrogen receptor (ER)-positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens, CYP27A1 expression levels correlated with tumor grade. In high-grade tumors, both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus, lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899689/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899689/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nelson, Erik R -- Wardell, Suzanne E -- Jasper, Jeff S -- Park, Sunghee -- Suchindran, Sunil -- Howe, Matthew K -- Carver, Nicole J -- Pillai, Ruchita V -- Sullivan, Patrick M -- Sondhi, Varun -- Umetani, Michihisa -- Geradts, Joseph -- McDonnell, Donald P -- K99CA172357/CA/NCI NIH HHS/ -- R37 DK048807/DK/NIDDK NIH HHS/ -- R37DK048807/DK/NIDDK NIH HHS/ -- T32 CA059365/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1094-8. doi: 10.1126/science.1241908.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24288332" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/blood/*metabolism/*pathology ; Cell Line, Tumor ; Cholestanetriol 26-Monooxygenase/antagonists & inhibitors/metabolism ; Disease Models, Animal ; Female ; Humans ; Hydroxycholesterols/antagonists & inhibitors/blood/*metabolism ; Hypercholesterolemia/blood/*metabolism ; Lung Neoplasms/secondary ; Mice ; Tumor Cells, Cultured
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  • 31
    Publication Date: 2013-03-02
    Description: Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giovanoli, Sandra -- Engler, Harald -- Engler, Andrea -- Richetto, Juliet -- Voget, Mareike -- Willi, Roman -- Winter, Christine -- Riva, Marco A -- Mortensen, Preben B -- Feldon, Joram -- Schedlowski, Manfred -- Meyer, Urs -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1095-9. doi: 10.1126/science.1228261.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, 8603 Schwerzenbach, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytokines/immunology ; Disease Models, Animal ; Female ; Humans ; Mental Disorders/*immunology ; Mice ; Mice, Inbred C57BL ; Poly I-C/immunology/pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology/virology ; Puberty/*immunology ; Stress, Physiological/*immunology
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  • 32
    Publication Date: 2013-05-21
    Description: Lazic criticizes the statistical analyses used to support the conclusions in our mouse model. His theory-biased criticism is disproportionate in view of the robustness of our findings (even if different statistical methods are applied) and falls short in explaining the postpubertal onset of effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giovanoli, Sandra -- Meyer, Urs -- New York, N.Y. -- Science. 2013 May 17;340(6134):811. doi: 10.1126/science.1238060.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23687030" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Humans ; Mental Disorders/*immunology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology ; Puberty/*immunology ; Stress, Physiological/*immunology
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiss, Robin A -- Stoye, Jonathan P -- MC_U117512710/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2013 May 17;340(6134):820-1. doi: 10.1126/science.1235148.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK. rweiss@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23687035" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA, Viral/genetics ; Endogenous Retroviruses/*genetics ; Female ; Genome, Human/*genetics ; Humans ; Placenta/virology ; Pregnancy ; Promoter Regions, Genetic ; Proviruses/*genetics ; Transcription, Genetic
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  • 34
    Publication Date: 2013-07-03
    Description: Oxygen deprivation followed by reoxygenation causes pathological responses in many disorders, including ischemic stroke, heart attacks, and reperfusion injury. Key aspects of ischemia-reperfusion can be modeled by a Caenorhabditis elegans behavior, the O2-ON response, which is suppressed by hypoxic preconditioning or inactivation of the O2-sensing HIF (hypoxia-inducible factor) hydroxylase EGL-9. From a genetic screen, we found that the cytochrome P450 oxygenase CYP-13A12 acts in response to the EGL-9-HIF-1 pathway to facilitate the O2-ON response. CYP-13A12 promotes oxidation of polyunsaturated fatty acids into eicosanoids, signaling molecules that can strongly affect inflammatory pain and ischemia-reperfusion injury responses in mammals. We propose that roles of the EGL-9-HIF-1 pathway and cytochrome P450 in controlling responses to reoxygenation after anoxia are evolutionarily conserved.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969381/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969381/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Dengke K -- Rothe, Michael -- Zheng, Shu -- Bhatla, Nikhil -- Pender, Corinne L -- Menzel, Ralph -- Horvitz, H Robert -- GM24663/GM/NIGMS NIH HHS/ -- R01 GM024663/GM/NIGMS NIH HHS/ -- R37 GM024663/GM/NIGMS NIH HHS/ -- T32 GM007484/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):554-8. doi: 10.1126/science.1235753. Epub 2013 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23811225" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Disease Models, Animal ; Eicosanoids/metabolism ; Evolution, Molecular ; Fatty Acids, Unsaturated/metabolism ; Hypoxia-Inducible Factor 1/*metabolism ; Oxygen/*metabolism ; Reperfusion Injury/*metabolism
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  • 35
    Publication Date: 2013-08-10
    Description: Tree-building with diverse data maximizes explanatory power. Application of molecular clock models to ancient speciation events risks a bias against detection of fast radiations subsequent to the Cretaceous-Paleogene (K-Pg) event. Contrary to Springer et al., post-K-Pg placental diversification does not require "virus-like" substitution rates. Even constraining clade ages to their model, the explosive model best explains placental evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Leary, Maureen A -- Bloch, Jonathan I -- Flynn, John J -- Gaudin, Timothy J -- Giallombardo, Andres -- Giannini, Norberto P -- Goldberg, Suzann L -- Kraatz, Brian P -- Luo, Zhe-Xi -- Meng, Jin -- Ni, Xijun -- Novacek, Michael J -- Perini, Fernando A -- Randall, Zachary -- Rougier, Guillermo W -- Sargis, Eric J -- Silcox, Mary T -- Simmons, Nancy B -- Spaulding, Michelle -- Velazco, Paul M -- Weksler, Marcelo -- Wible, John R -- Cirranello, Andrea L -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):613. doi: 10.1126/science.1238162.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomical Sciences, HSC T-8 (040), Stony Brook University, Stony Brook, NY 11794-8081, USA. maureen.oleary@stonybrook.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929968" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Female ; *Fossils ; *Mammals ; *Phylogeny ; Pregnancy
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  • 36
    Publication Date: 2013-07-28
    Description: Gram-negative bacteria including Escherichia coli, Citrobacter rodentium, Salmonella typhimurium, and Shigella flexneri are sensed in an ill-defined manner by an intracellular inflammasome complex that activates caspase-11. We show that macrophages loaded with synthetic lipid A, E. coli lipopolysaccharide (LPS), or S. typhimurium LPS activate caspase-11 independently of the LPS receptor Toll-like receptor 4 (TLR4). Consistent with lipid A triggering the noncanonical inflammasome, LPS containing a divergent lipid A structure antagonized caspase-11 activation in response to E. coli LPS or Gram-negative bacteria. Moreover, LPS-mutant E. coli failed to activate caspase-11. Tlr4(-/-) mice primed with TLR3 agonist polyinosinic:polycytidylic acid [poly(I:C)] to induce pro-caspase-11 expression were as susceptible as wild-type mice were to sepsis induced by E. coli LPS. These data unveil a TLR4-independent mechanism for innate immune recognition of LPS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kayagaki, Nobuhiko -- Wong, Michael T -- Stowe, Irma B -- Ramani, Sree Ranjani -- Gonzalez, Lino C -- Akashi-Takamura, Sachiko -- Miyake, Kensuke -- Zhang, Juan -- Lee, Wyne P -- Muszynski, Artur -- Forsberg, Lennart S -- Carlson, Russell W -- Dixit, Vishva M -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1246-9. doi: 10.1126/science.1240248. Epub 2013 Jul 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA. kayagaki@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23887873" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspases/biosynthesis ; Cholera Toxin/immunology ; Disease Models, Animal ; Escherichia coli/immunology ; Escherichia coli Infections/genetics/immunology ; *Immunity, Innate ; Inflammasomes/*immunology ; Lipid A/genetics/*immunology ; Macrophages/*immunology ; Mice ; Mice, Mutant Strains ; Mutation ; Salmonella Infections/immunology ; Salmonella typhimurium/immunology ; Sepsis/immunology ; Toll-Like Receptor 4/*immunology
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  • 37
    Publication Date: 2013-08-10
    Description: O'Leary et al. (Research Article, 8 February 2013, p. 662) examined mammalian relationships and divergence times and concluded that a single placental ancestor crossed the Cretaceous-Paleogene (K-Pg) boundary. This conclusion relies on phylogenetic analyses that fail to discriminate between homology and homoplasy and further implies virus-like rates of nucleotide substitution in early Paleocene placentals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Springer, Mark S -- Meredith, Robert W -- Teeling, Emma C -- Murphy, William J -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):613. doi: 10.1126/science.1238025.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, Riverside, CA 92521, USA. mark.springer@ucr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929967" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Female ; *Fossils ; *Mammals ; *Phylogeny ; Pregnancy
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  • 38
    Publication Date: 2013-05-25
    Description: The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure. Pigs were productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to naive pigs or ferrets. Under appropriate conditions, human-to-human transmission of the H7N9 virus may be possible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, H -- Wang, D -- Kelvin, D J -- Li, L -- Zheng, Z -- Yoon, S-W -- Wong, S-S -- Farooqui, A -- Wang, J -- Banner, D -- Chen, R -- Zheng, R -- Zhou, J -- Zhang, Y -- Hong, W -- Dong, W -- Cai, Q -- Roehrl, M H A -- Huang, S S H -- Kelvin, A A -- Yao, T -- Zhou, B -- Chen, X -- Leung, G M -- Poon, L L M -- Webster, R G -- Webby, R J -- Peiris, J S M -- Guan, Y -- Shu, Y -- HSN266200700005C/PHS HHS/ -- New York, N.Y. -- Science. 2013 Jul 12;341(6142):183-6. doi: 10.1126/science.1239844. Epub 2013 May 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint Influenza Research Centre [Shantou University Medical College/University of Hong Kong], Shantou University, Shantou, PR China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704376" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Communicable Diseases, Emerging/*transmission/*virology ; Disease Models, Animal ; Ferrets ; Humans ; Influenza, Human/pathology/*transmission/*virology ; Orthomyxoviridae/classification/genetics/*pathogenicity ; Respiratory System/pathology/virology ; Sus scrofa
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-02-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoder, Anne D -- New York, N.Y. -- Science. 2013 Feb 8;339(6120):656-8. doi: 10.1126/science.1233999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Duke University, Durham, NC 27708, USA. anne.yoder@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Female ; *Fossils ; *Mammals ; *Phylogeny ; Pregnancy
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  • 40
    Publication Date: 2013-05-21
    Description: Giovanoli et al. (Reports, 1 March 2013, p. 1095) applied an immune challenge to pregnant females, and therefore to all offspring, and subsequently applied stress to offspring on a per cage basis. The data, however, were analyzed as a completely randomized design, which is inappropriate given these restrictions on randomization. This will increase both false positives and false negatives.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazic, Stanley E -- New York, N.Y. -- Science. 2013 May 17;340(6134):811. doi: 10.1126/science.1237793.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉In Silico Lead Discovery, Novartis Institutes for Biomedical Research, Basel, Switzerland. stan.lazic@cantab.net〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23687029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Humans ; Mental Disorders/*immunology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology ; Puberty/*immunology ; Stress, Physiological/*immunology
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084614/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084614/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holland, William L -- Scherer, Philipp E -- P01 DK088761/DK/NIDDK NIH HHS/ -- R01 DK055758/DK/NIDDK NIH HHS/ -- R01 DK099110/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1460-1. doi: 10.1126/science.1249077.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357309" target="_blank"〉PubMed〈/a〉
    Keywords: Adiponectin/*biosynthesis/chemistry/pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology ; Anti-Obesity Agents/chemistry/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Ceramidases/metabolism ; Diabetes Mellitus, Experimental/drug therapy ; Disease Models, Animal ; Hypoglycemic Agents/chemistry/*pharmacology/therapeutic use ; Insulin Resistance ; Mice ; Molecular Mimicry ; *Molecular Targeted Therapy ; Obesity/drug therapy ; Piperidines/chemistry/*pharmacology/therapeutic use ; Receptors, Adiponectin/*agonists
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  • 42
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1164-7. doi: 10.1126/science.341.6151.1164.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24030995" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*diagnosis/*immunology ; Brain/embryology/*immunology ; California ; Child, Preschool ; Female ; Fetal Proteins/*immunology ; Humans ; *Immunologic Tests ; Maternal-Fetal Exchange/immunology ; Pregnancy
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  • 43
    Publication Date: 2014-09-23
    Description: The neuromuscular junction (NMJ) is the synapse between a motor neuron and skeletal muscle. Defects in NMJ transmission cause muscle weakness, termed myasthenia. The muscle protein Dok-7 is essential for activation of the receptor kinase MuSK, which governs NMJ formation, and DOK7 mutations underlie familial limb-girdle myasthenia (DOK7 myasthenia), a neuromuscular disease characterized by small NMJs. Here, we show in a mouse model of DOK7 myasthenia that therapeutic administration of an adeno-associated virus (AAV) vector encoding the human DOK7 gene resulted in an enlargement of NMJs and substantial increases in muscle strength and life span. When applied to model mice of another neuromuscular disorder, autosomal dominant Emery-Dreifuss muscular dystrophy, DOK7 gene therapy likewise resulted in enlargement of NMJs as well as positive effects on motor activity and life span. These results suggest that therapies aimed at enlarging the NMJ may be useful for a range of neuromuscular disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arimura, Sumimasa -- Okada, Takashi -- Tezuka, Tohru -- Chiyo, Tomoko -- Kasahara, Yuko -- Yoshimura, Toshiro -- Motomura, Masakatsu -- Yoshida, Nobuaki -- Beeson, David -- Takeda, Shin'ichi -- Yamanashi, Yuji -- G0701521/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1505-8. doi: 10.1126/science.1250744.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. ; Department of Occupational Therapy, Nagasaki University School of Health Sciences, Nagasaki, Japan. ; Department of Electrical and Electronics Engineering, Faculty of Engineering, Nagasaki Institute of Applied Science, Nagasaki, Japan. ; Laboratory of Developmental Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ; Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. ; Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. yyamanas@ims.u-tokyo.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dependovirus ; Disease Models, Animal ; Female ; Genetic Therapy/*methods ; Genetic Vectors/administration & dosage ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle Proteins/*genetics ; Muscle, Skeletal/*innervation/physiopathology ; Muscular Dystrophies, Limb-Girdle/genetics/*pathology/*therapy ; Neuromuscular Junction/*pathology
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Silvente-Poirot, Sandrine -- Poirot, Marc -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1445-6. doi: 10.1126/science.1252787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UMR 1037 INSERM-University Toulouse III, Cancer Research Center of Toulouse, and Institut Claudius Regaud, 31052 Toulouse, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675946" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*metabolism/*pathology ; Cholesterol/*metabolism ; Cholesterol, Dietary/administration & dosage/metabolism ; Disease Models, Animal ; Female ; Humans ; Hypercholesterolemia/metabolism ; Metabolic Networks and Pathways ; Mice
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  • 45
    Publication Date: 2014-11-15
    Description: Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Benyue -- Chassaing, Benoit -- Shi, Zhenda -- Uchiyama, Robin -- Zhang, Zhan -- Denning, Timothy L -- Crawford, Sue E -- Pruijssers, Andrea J -- Iskarpatyoti, Jason A -- Estes, Mary K -- Dermody, Terence S -- Ouyang, Wenjun -- Williams, Ifor R -- Vijay-Kumar, Matam -- Gewirtz, Andrew T -- AI038296/AI/NIAID NIH HHS/ -- AI080656/AI/NIAID NIH HHS/ -- AI107943/AI/NIAID NIH HHS/ -- DK061417/DK/NIDDK NIH HHS/ -- DK064730/DK/NIDDK NIH HHS/ -- DK56338/DK/NIDDK NIH HHS/ -- R01 AI038296/AI/NIAID NIH HHS/ -- R37 AI038296/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):861-5. doi: 10.1126/science.1256999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pediatrics, Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA. ; Department of Immunology, Genentech, South San Francisco, CA, USA. ; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. ; Department of Nutritional Sciences and Medicine, Pennsylvania State University, University Park, PA 16802, USA. ; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA. agewirtz@gsu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diarrhea/immunology/therapy/virology ; Disease Models, Animal ; Feces/virology ; Flagellin/*administration & dosage/immunology ; Homeodomain Proteins/genetics ; *Immunity, Innate ; Interleukin-18/administration & dosage/genetics/*immunology ; Interleukins/administration & dosage/genetics/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mutation ; Rotavirus Infections/immunology/*prevention & control/therapy ; Toll-Like Receptor 5/genetics/*physiology ; Virus Shedding
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  • 46
    Publication Date: 2014-09-13
    Description: Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774895/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774895/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goto, Yoshiyuki -- Obata, Takashi -- Kunisawa, Jun -- Sato, Shintaro -- Ivanov, Ivaylo I -- Lamichhane, Aayam -- Takeyama, Natsumi -- Kamioka, Mariko -- Sakamoto, Mitsuo -- Matsuki, Takahiro -- Setoyama, Hiromi -- Imaoka, Akemi -- Uematsu, Satoshi -- Akira, Shizuo -- Domino, Steven E -- Kulig, Paulina -- Becher, Burkhard -- Renauld, Jean-Christophe -- Sasakawa, Chihiro -- Umesaki, Yoshinori -- Benno, Yoshimi -- Kiyono, Hiroshi -- 1R01DK098378/DK/NIDDK NIH HHS/ -- R01 DK098378/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2014 Sep 12;345(6202):1254009. doi: 10.1126/science.1254009. Epub 2014 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. ; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Nippon Institute for Biological Science, Tokyo 198-0024, Japan. ; Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan. ; Yakult Central Institute, Tokyo 186-8650, Japan. ; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. ; Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617, USA. ; Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland. ; Ludwig Institute for Cancer Research and Universite Catholique de Louvain, Brussels B-1200, Belgium. ; Nippon Institute for Biological Science, Tokyo 198-0024, Japan. Division of Bacterial Infection, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan. ; Benno Laboratory, Innovation Center, RIKEN, Wako, Saitama 351-0198, Japan. ; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25214634" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Fucose/*metabolism ; Fucosyltransferases/genetics/metabolism ; Germ-Free Life ; Glycosylation ; Goblet Cells/enzymology/immunology/microbiology ; Ileum/enzymology/immunology/microbiology ; *Immunity, Innate ; Interleukins/immunology ; Intestinal Mucosa/enzymology/*immunology/microbiology ; Lymphocytes/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microbiota/*immunology ; Molecular Sequence Data ; Paneth Cells/enzymology/immunology/microbiology ; Salmonella Infections/*immunology/microbiology ; *Salmonella typhimurium
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmerman, Andrew W -- Connors, Susan L -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):620-1. doi: 10.1126/science.1250214.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics (Neurology), Center for Autism and Neurodevelopmental Disorders, University of Massachusetts Medical School, Worcester, MA 01655, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503843" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics ; *Cytoprotection ; Female ; Oxytocin/*metabolism ; Pregnancy ; gamma-Aminobutyric Acid/*metabolism
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Susiarjo, Martha -- Bartolomei, Marisa S -- P30 ES013508/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):733-4. doi: 10.1126/science.1258654.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. bartolom@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124413" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *DNA Methylation ; Female ; Fetal Nutrition Disorders/*metabolism ; Male ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Spermatozoa/*metabolism
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  • 49
    Publication Date: 2014-10-11
    Description: Tyzio et al. (Reports, 7 February 2014, p. 675) reported that bumetanide restored the impaired oxytocin-mediated gamma-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery in animal models of autism, ameliorating some autistic-like characteristics in the offspring. However, standard practices in the study of these models, such as the use of sex-dimorphic or males-only analyses and implementation of tests measuring social behavior, are lacking to definitely associate their findings to autism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bambini-Junior, Victorio -- Nunes, Gustavo Della Flora -- Schneider, Tomasz -- Gottfried, Carmem -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):176. doi: 10.1126/science.1255679.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Federal University of Rio Grande do Sul, Research Group in Neuroglial Plasticity at the Department of Biochemistry, Institute of Health's Basic Science, Porto Alegre, Rio Grande do Sul, Brazil. Federal University of Rio Grande do Sul, Translational Research Group in Autism Spectrum Disorders (GETTEA), Porto Alegre, RS, Brazil. victoriobambini@gmail.com. ; Federal University of Rio Grande do Sul, Research Group in Neuroglial Plasticity at the Department of Biochemistry, Institute of Health's Basic Science, Porto Alegre, Rio Grande do Sul, Brazil. Federal University of Rio Grande do Sul, Translational Research Group in Autism Spectrum Disorders (GETTEA), Porto Alegre, RS, Brazil. ; School of Medicine, Pharmacy and Health, TS17 6BH, Durham University, Durham, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301610" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics ; *Cytoprotection ; Female ; Oxytocin/*metabolism ; Pregnancy ; gamma-Aminobutyric Acid/*metabolism
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  • 50
    Publication Date: 2014-08-30
    Description: Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. Similarly, an H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M-containing nucleosomes, and its misregulation in Drosophila results in changes of H3K9 methylation levels and heterochromatic silencing defects. We have established histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herz, Hans-Martin -- Morgan, Marc -- Gao, Xin -- Jackson, Jessica -- Rickels, Ryan -- Swanson, Selene K -- Florens, Laurence -- Washburn, Michael P -- Eissenberg, Joel C -- Shilatifard, Ali -- CA R01CA089455/CA/NCI NIH HHS/ -- R01 CA089455/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1065-70. doi: 10.1126/science.1255104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ; Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis, MO, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. ; Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. ash@northwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170156" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Chromatin/*metabolism ; Disease Models, Animal ; Drosophila Proteins/genetics ; Drosophila melanogaster ; Gene Silencing ; Glioma/genetics/metabolism ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase/genetics ; Histones/*genetics/metabolism ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Lysine/*genetics ; Methionine/*genetics ; Methylation ; Mutation ; Signal Transduction
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  • 51
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-16
    Description: Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191866/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191866/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Romero, Roberto -- Dey, Sudhansu K -- Fisher, Susan J -- DA06668/DA/NIDA NIH HHS/ -- HD068524/HD/NICHD NIH HHS/ -- P50 HD055764/HD/NICHD NIH HHS/ -- R01 HD068524/HD/NICHD NIH HHS/ -- R37 HD076253/HD/NICHD NIH HHS/ -- U54 HD055764/HD/NICHD NIH HHS/ -- ZIA HD002400-23/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):760-5. doi: 10.1126/science.1251816. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, Wayne State University/the Detroit Medical Center, Detroit, MI, USA. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. romeror@mail.nih.gov. ; Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. ; Department of Obstetrics, Gynecology and Reproductive Sciences, Department of Anatomy, and Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124429" target="_blank"〉PubMed〈/a〉
    Keywords: Decidua/physiopathology ; Female ; Fetus/immunology ; Humans ; Immune Tolerance ; Infection/complications/physiopathology ; Inflammation/complications/physiopathology ; Obstetric Labor, Premature/*etiology/physiopathology/*prevention & control ; Placenta/immunology ; Pregnancy ; Syndrome ; Vascular Diseases/complications/physiopathology
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  • 52
    Publication Date: 2014-02-08
    Description: We report that the oxytocin-mediated neuroprotective gamma-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naive mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tyzio, Roman -- Nardou, Romain -- Ferrari, Diana C -- Tsintsadze, Timur -- Shahrokhi, Amene -- Eftekhari, Sanaz -- Khalilov, Ilgam -- Tsintsadze, Vera -- Brouchoud, Corinne -- Chazal, Genevieve -- Lemonnier, Eric -- Lozovaya, Natalia -- Burnashev, Nail -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Feb 7;343(6171):675-9. doi: 10.1126/science.1247190.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24503856" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics/metabolism ; Behavior, Animal ; Bumetanide/administration & dosage ; Chlorides/metabolism ; *Cytoprotection ; Disease Models, Animal ; Female ; Fragile X Mental Retardation Protein/genetics ; Maternal-Fetal Exchange ; Mice ; Oxytocin/*metabolism ; Parturition ; Pregnancy ; Rats ; Valproic Acid/pharmacology ; gamma-Aminobutyric Acid/*metabolism
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):750-1. doi: 10.1126/science.345.6198.750.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124425" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diet ; Female ; Fetus/*physiology ; *Food Preferences ; Humans ; Infant ; Infant, Newborn/*physiology ; Mice ; *Mothers ; Olfactory Receptor Neurons/physiology ; Pregnancy ; *Taste ; Taste Perception
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  • 54
    Publication Date: 2014-10-11
    Description: Bambini-Junior et al. questioned whether our treatment in two rodent models of autism has a long-lasting effect into adulthood. In response, we show that bumetanide treatment around delivery attenuates autistic behavioral features in adult offspring. Therefore, the polarity of gamma-aminobutyric acid (GABA) actions during delivery exerts long-lasting priming actions after birth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eftekhari, Sanaz -- Shahrokhi, Amene -- Tsintsadze, Vera -- Nardou, Romain -- Brouchoud, Corinne -- Conesa, Magali -- Burnashev, Nail -- Ferrari, Diana C -- Ben-Ari, Yehezkel -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):176. doi: 10.1126/science.1256009.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. On leave from Iran University of Medical Sciences, Tehran, Iran. ; Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. On leave from Tehran University of Medical Sciences, Tehran, Iran. ; Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. ; Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. ; Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France. UMR 901, Aix-Marseille University, Marseille, France. Neurochlore, Campus Scientifique de Luminy, 163 Route de Luminy, Marseille, France. yehezkel.ben-ari@inserm.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301611" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*chemically induced/*genetics ; *Cytoprotection ; Female ; Oxytocin/*metabolism ; Pregnancy ; gamma-Aminobutyric Acid/*metabolism
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  • 55
    Publication Date: 2014-08-16
    Description: Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346163/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346163/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoegger, Mark J -- Fischer, Anthony J -- McMenimen, James D -- Ostedgaard, Lynda S -- Tucker, Alex J -- Awadalla, Maged A -- Moninger, Thomas O -- Michalski, Andrew S -- Hoffman, Eric A -- Zabner, Joseph -- Stoltz, David A -- Welsh, Michael J -- DK054759/DK/NIDDK NIH HHS/ -- DP2 HL117744/DP/NCCDPHP CDC HHS/ -- DP2 HL117744/HL/NHLBI NIH HHS/ -- HL051670/HL/NHLBI NIH HHS/ -- HL091842/HL/NHLBI NIH HHS/ -- P01 HL051670/HL/NHLBI NIH HHS/ -- P01 HL091842/HL/NHLBI NIH HHS/ -- P30 DK054759/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):818-22. doi: 10.1126/science.1255825.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. ; Department of Pediatrics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. ; Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. ; Central Microscopy Research Facility, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. ; Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Radiology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA. ; Department of Molecular Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA. david-stoltz@uiowa.edu michael-welsh@uiowa.edu. ; Department of Molecular Physiology and Biophysics, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. Howard Hughes Medical Institute (HHMI), University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA. david-stoltz@uiowa.edu michael-welsh@uiowa.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124441" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Anions/metabolism ; Cilia/physiology ; Cystic Fibrosis/*physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator/physiology ; Disease Models, Animal ; Exocrine Glands/*secretion ; Lung/physiopathology ; Methacholine Chloride/pharmacology ; *Mucociliary Clearance ; Mucus/*secretion ; Respiratory Mucosa/*physiopathology ; Respiratory System/*physiopathology ; Swine ; Trachea/physiopathology
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  • 56
    Publication Date: 2014-08-12
    Description: Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration and high rates of mortality. Through chemical screening and optimization, we identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 messenger RNA with high selectivity. Administration of these compounds to Delta7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naryshkin, Nikolai A -- Weetall, Marla -- Dakka, Amal -- Narasimhan, Jana -- Zhao, Xin -- Feng, Zhihua -- Ling, Karen K Y -- Karp, Gary M -- Qi, Hongyan -- Woll, Matthew G -- Chen, Guangming -- Zhang, Nanjing -- Gabbeta, Vijayalakshmi -- Vazirani, Priya -- Bhattacharyya, Anuradha -- Furia, Bansri -- Risher, Nicole -- Sheedy, Josephine -- Kong, Ronald -- Ma, Jiyuan -- Turpoff, Anthony -- Lee, Chang-Sun -- Zhang, Xiaoyan -- Moon, Young-Choon -- Trifillis, Panayiota -- Welch, Ellen M -- Colacino, Joseph M -- Babiak, John -- Almstead, Neil G -- Peltz, Stuart W -- Eng, Loren A -- Chen, Karen S -- Mull, Jesse L -- Lynes, Maureen S -- Rubin, Lee L -- Fontoura, Paulo -- Santarelli, Luca -- Haehnke, Daniel -- McCarthy, Kathleen D -- Schmucki, Roland -- Ebeling, Martin -- Sivaramakrishnan, Manaswini -- Ko, Chien-Ping -- Paushkin, Sergey V -- Ratni, Hasane -- Gerlach, Irene -- Ghosh, Anirvan -- Metzger, Friedrich -- New York, N.Y. -- Science. 2014 Aug 8;345(6197):688-93. doi: 10.1126/science.1250127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. ; Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA. ; PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. friedrich.metzger@roche.com speltz@ptcbio.com. ; SMA Foundation, 888 Seventh Avenue, Suite 400, New York, NY 10019, USA. ; Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. ; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. ; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. friedrich.metzger@roche.com speltz@ptcbio.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25104390" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Alternative Splicing/*drug effects ; Animals ; Cells, Cultured ; Coumarins/*administration & dosage/chemistry ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Isocoumarins/*administration & dosage/chemistry ; Longevity/*drug effects ; Mice ; Muscular Atrophy, Spinal/*drug therapy/genetics/metabolism ; Pyrimidinones/*administration & dosage/chemistry ; RNA, Messenger/genetics ; Sequence Deletion ; Small Molecule Libraries/*administration & dosage/chemistry ; Survival of Motor Neuron 2 Protein/*genetics/metabolism
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):172. doi: 10.1126/science.329.5988.172.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616268" target="_blank"〉PubMed〈/a〉
    Keywords: *Child, Abandoned ; *Child, Orphaned ; Female ; *HIV Infections/complications/prevention & control/transmission ; Humans ; Infant ; Infectious Disease Transmission, Vertical/prevention & control ; Pregnancy ; Pregnancy Complications ; *Pregnancy Complications, Infectious ; Pregnancy, Unwanted ; Risk Factors ; Russia ; Substance Abuse, Intravenous/*complications
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 58
    Publication Date: 2010-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Mar 5;327(5970):1197. doi: 10.1126/science.327.5970.1197.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203030" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/therapeutic use ; Developing Countries ; Female ; *HIV Infections/drug therapy/epidemiology/prevention & control/transmission ; Humans ; Infant ; Infectious Disease Transmission, Vertical/*prevention & control ; Nevirapine/therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis/*drug therapy
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2010 Feb 26;327(5969):1066-7. doi: 10.1126/science.327.5969.1066.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185694" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Asthmatic Agents/*adverse effects/therapeutic use ; Antiviral Agents/*adverse effects/therapeutic use ; Asthma/drug therapy ; *Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Influenza Vaccines/*adverse effects ; Influenza, Human/drug therapy/prevention & control ; Pregnancy ; Pregnancy Complications/*drug therapy/prevention & control ; Societies, Medical ; United States ; United States Agency for Healthcare Research and Quality ; United States Dept. of Health and Human Services
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  • 60
    Publication Date: 2010-04-03
    Description: Cytomegalovirus (CMV) can superinfect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. We have demonstrated that superinfection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally encoded inhibitors of major histocompatibility complex class I (MHC-I) antigen presentation, particularly the homologs of human CMV US2, 3, 6, and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo, thus supporting viral replication and dissemination during superinfection, a process that complicates the development of preventive CMV vaccines but that can be exploited for CMV-based vector development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883175/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Powers, Colin J -- Richards, Rebecca -- Ventura, Abigail B -- Ford, Julia C -- Siess, Don -- Axthelm, Michael K -- Nelson, Jay A -- Jarvis, Michael A -- Picker, Louis J -- Fruh, Klaus -- AI040101/AI/NIAID NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- P51 RR000163-460222/RR/NCRR NIH HHS/ -- P51 RR000163-486829/RR/NCRR NIH HHS/ -- P51 RR000163-496081/RR/NCRR NIH HHS/ -- P51 RR000163-508648/RR/NCRR NIH HHS/ -- R01 AI021640/AI/NIAID NIH HHS/ -- R01 AI021640-26/AI/NIAID NIH HHS/ -- R01 AI059457/AI/NIAID NIH HHS/ -- R01 AI059457-01A2/AI/NIAID NIH HHS/ -- R01 AI059457-02/AI/NIAID NIH HHS/ -- R01 AI059457-03/AI/NIAID NIH HHS/ -- R01 AI059457-04/AI/NIAID NIH HHS/ -- R01 AI059457-05/AI/NIAID NIH HHS/ -- R01 AI060392/AI/NIAID NIH HHS/ -- RR00163/RR/NCRR NIH HHS/ -- RR016001/RR/NCRR NIH HHS/ -- RR016025/RR/NCRR NIH HHS/ -- RR18107/RR/NCRR NIH HHS/ -- T32 AI007472/AI/NIAID NIH HHS/ -- T32 HL007781/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):102-6. doi: 10.1126/science.1185350.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360110" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cytomegalovirus/genetics/immunology/*physiology ; Cytomegalovirus Infections/*immunology/*virology ; Cytomegalovirus Vaccines/immunology ; Disease Models, Animal ; Gene Products, gag/immunology ; Genes, Viral ; Histocompatibility Antigens Class I/immunology ; *Immune Evasion ; Immunologic Factors/genetics/*physiology ; Macaca mulatta ; Male ; Simian Immunodeficiency Virus/genetics/immunology ; Superinfection ; Viral Proteins/genetics/*physiology ; Virus Replication ; Virus Shedding
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  • 61
    Publication Date: 2010-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enserink, Martin -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):266-7. doi: 10.1126/science.327.5963.266-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075230" target="_blank"〉PubMed〈/a〉
    Keywords: Abortion, Veterinary/microbiology/prevention & control ; Animal Husbandry ; Animals ; Bacterial Vaccines ; Bioterrorism ; Coxiella burnetii/immunology/pathogenicity ; *Disease Outbreaks/prevention & control/veterinary ; Female ; *Goat Diseases ; Goats ; Humans ; Netherlands/epidemiology ; Pregnancy ; Q Fever/*epidemiology/prevention & control/transmission/veterinary
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 62
    Publication Date: 2010-07-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- Travis, John -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):386-7. doi: 10.1126/science.329.5990.386.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651132" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Cadherins/genetics ; *Compulsive Behavior/drug therapy/genetics ; Disease Models, Animal ; *Dog Diseases/drug therapy ; Dogs/genetics ; Excitatory Amino Acid Antagonists/*therapeutic use ; History, 20th Century ; History, 21st Century ; Humans ; Memantine/*therapeutic use ; Obsessive-Compulsive Disorder/*drug therapy/genetics ; Stereotyped Behavior ; United States ; Veterinary Medicine/history
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  • 63
    Publication Date: 2011-02-19
    Description: During pregnancy, progesterone inhibits the growth-promoting actions of estrogen in the uterus. However, the mechanism for this is not clear. The attenuation of estrogen-mediated proliferation of the uterine epithelium by progesterone is a prerequisite for successful implantation. Our study reveals that progesterone-induced expression of the basic helix-loop-helix transcription factor Hand2 in the uterine stroma suppresses the production of several fibroblast growth factors (FGFs) that act as paracrine mediators of mitogenic effects of estrogen on the epithelium. In mouse uteri lacking Hand2, continued induction of these FGFs in the stroma maintains epithelial proliferation and stimulates estrogen-induced pathways, resulting in impaired implantation. Thus, Hand2 is a critical regulator of the uterine stromal-epithelial communication that directs proper steroid regulation conducive for the establishment of pregnancy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320855/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320855/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Quanxi -- Kannan, Athilakshmi -- DeMayo, Francesco J -- Lydon, John P -- Cooke, Paul S -- Yamagishi, Hiroyuki -- Srivastava, Deepak -- Bagchi, Milan K -- Bagchi, Indrani C -- U54 HD055787-01A1/HD/NICHD NIH HHS/ -- U54HD055787/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2011 Feb 18;331(6019):912-6. doi: 10.1126/science.1197454.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Comparative Biosciences, University of Illinois Urbana/Champaign, Urbana, IL 61820, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21330545" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics/*metabolism ; Cell Proliferation ; Embryo Implantation/*physiology ; Endometrium/drug effects/*metabolism ; Epithelial Cells/cytology/drug effects/metabolism ; Epithelium/metabolism ; Estradiol/metabolism ; Estrogen Receptor alpha/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Fibroblast Growth Factors/genetics/*metabolism ; Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mifepristone/pharmacology ; Mucin-1/metabolism ; Phosphorylation ; Pregnancy ; Progesterone/antagonists & inhibitors/*metabolism/pharmacology ; Receptors, Fibroblast Growth Factor/metabolism ; Receptors, Progesterone/metabolism ; *Signal Transduction ; Stromal Cells/cytology/metabolism ; Transcription, Genetic
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  • 64
    Publication Date: 2011-03-26
    Description: Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406187/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beatty, Gregory L -- Chiorean, Elena G -- Fishman, Matthew P -- Saboury, Babak -- Teitelbaum, Ursina R -- Sun, Weijing -- Huhn, Richard D -- Song, Wenru -- Li, Dongguang -- Sharp, Leslie L -- Torigian, Drew A -- O'Dwyer, Peter J -- Vonderheide, Robert H -- K08 CA138907/CA/NCI NIH HHS/ -- K12 CA076931/CA/NCI NIH HHS/ -- P30 CA016520/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1612-6. doi: 10.1126/science.1198443.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436454" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Animals ; Antibodies, Monoclonal/administration & dosage/adverse ; effects/metabolism/*therapeutic use ; Antigens, CD40/*agonists/*immunology ; Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Pancreatic Ductal/*drug therapy/immunology/pathology/secondary ; Deoxycytidine/analogs & derivatives/therapeutic use ; Disease Models, Animal ; Disease-Free Survival ; Female ; Humans ; Immunologic Surveillance ; Macrophage Activation ; Macrophages/immunology ; Male ; Mice ; Middle Aged ; Pancreatic Neoplasms/*drug therapy/immunology/pathology ; T-Lymphocytes/immunology ; Tumor Microenvironment ; Young Adult
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2011 Oct 14;334(6053):166. doi: 10.1126/science.334.6053.166.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21998360" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/epidemiology ; Condoms ; Contraceptives, Oral, Hormonal/administration & dosage/*adverse effects ; Female ; HIV Infections/*epidemiology/transmission ; Humans ; Injections ; Male ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology ; Risk Factors
    Print ISSN: 0036-8075
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  • 66
    Publication Date: 2011-06-28
    Description: Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects one-third of adults and an increasing number of children in developed countries. The disease begins with the aberrant accumulation of triglyceride in the liver, which in some individuals elicits an inflammatory response that can progress to cirrhosis and liver cancer. Although NAFLD is strongly associated with obesity and insulin resistance, its pathogenesis remains poorly understood, and therapeutic options are limited. Here, we discuss recent mechanistic insights into NAFLD, focusing primarily on those that have emerged from human genetic and metabolic studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jonathan C -- Horton, Jay D -- Hobbs, Helen H -- P01 HL020948/HL/NHLBI NIH HHS/ -- P01 HL020948-35/HL/NHLBI NIH HHS/ -- P01 HL20948/HL/NHLBI NIH HHS/ -- R01 DK090066/DK/NIDDK NIH HHS/ -- RL1 HL092550/HL/NHLBI NIH HHS/ -- RL1 HL092550-05/HL/NHLBI NIH HHS/ -- RL1HL092550/HL/NHLBI NIH HHS/ -- UL1 DE019584/DE/NIDCR NIH HHS/ -- UL1 DE019584-05/DE/NIDCR NIH HHS/ -- UL1DE109584/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2011 Jun 24;332(6037):1519-23. doi: 10.1126/science.1204265.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21700865" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dietary Fats/administration & dosage ; Disease Models, Animal ; Disease Progression ; *Fatty Liver/etiology/genetics/metabolism/pathology ; Female ; Genetic Predisposition to Disease ; Humans ; Insulin Resistance ; Liver/metabolism/pathology ; Liver Cirrhosis/etiology ; Liver Neoplasms/etiology ; Male ; Non-alcoholic Fatty Liver Disease ; Obesity ; Triglycerides/metabolism
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-10-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2011 Oct 14;334(6053):168. doi: 10.1126/science.334.6053.168.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21998362" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bacterial Physiological Phenomena ; Female ; Humans ; *Immune Evasion ; Intestinal Mucosa/*virology ; Intestines/*microbiology ; Mammalian orthoreovirus 3/*physiology ; Mammary Tumor Virus, Mouse/*immunology/*pathogenicity ; *Metagenome ; Poliomyelitis/*virology ; Poliovirus/*physiology ; Pregnancy ; Reoviridae Infections/*virology ; Retroviridae Infections/*transmission ; *Virus Replication
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  • 68
    Publication Date: 2012-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1028-9. doi: 10.1126/science.335.6072.1028.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383816" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Multiple/epidemiology/veterinary/virology ; Animals ; Bunyaviridae Infections/epidemiology/transmission/*veterinary/virology ; Cattle ; Cattle Diseases/epidemiology/transmission/*virology ; Disease Outbreaks/*veterinary ; Europe/epidemiology ; Female ; Fetal Diseases/epidemiology/*veterinary/virology ; Genome, Viral ; Goat Diseases/epidemiology/transmission/virology ; Goats ; Livestock/*virology ; *Orthobunyavirus/classification/genetics/isolation & purification ; Pregnancy ; Sheep ; Sheep Diseases/epidemiology/transmission/*virology ; Simbu virus/classification/genetics/isolation & purification
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):32-3. doi: 10.1126/science.338.6103.32.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042865" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antipsychotic Agents ; Brain/drug effects/*physiopathology ; Disease Models, Animal ; Drug Discovery/history/*trends ; Gene Expression Profiling ; Genome, Human ; History, 20th Century ; History, 21st Century ; Humans ; Intellectual Disability ; Mental Disorders/drug therapy/genetics/*therapy ; Mice ; Neural Pathways ; Neuroimaging ; Neurons/metabolism/physiology ; Rats
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  • 70
    Publication Date: 2012-06-09
    Description: The chemokine-mediated recruitment of effector T cells to sites of inflammation is a central feature of the immune response. The extent to which chemokine expression levels are limited by the intrinsic developmental characteristics of a tissue has remained unexplored. We show in mice that effector T cells cannot accumulate within the decidua, the specialized stromal tissue encapsulating the fetus and placenta. Impaired accumulation was in part attributable to the epigenetic silencing of key T cell-attracting inflammatory chemokine genes in decidual stromal cells, as evidenced by promoter accrual of repressive histone marks. These findings give insight into mechanisms of fetomaternal immune tolerance, as well as reveal the epigenetic modification of tissue stromal cells as a modality for limiting effector T cell trafficking.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727649/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727649/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nancy, Patrice -- Tagliani, Elisa -- Tay, Chin-Siean -- Asp, Patrik -- Levy, David E -- Erlebacher, Adrian -- P30CA016087/CA/NCI NIH HHS/ -- R01 AI062980/AI/NIAID NIH HHS/ -- R01AI062980/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 8;336(6086):1317-21. doi: 10.1126/science.1220030.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22679098" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemokine CCL5/genetics/metabolism ; Chemokine CXCL10/genetics/metabolism ; Chemokine CXCL11/genetics/metabolism ; Chemokine CXCL9/genetics/metabolism ; Chemokines/*genetics/metabolism ; Chromatin Immunoprecipitation ; Decidua/*immunology/*metabolism ; Endometrium/cytology/immunology ; Female ; *Gene Silencing ; Histones/metabolism ; *Immune Tolerance ; Immunologic Memory ; Inflammation ; Methylation ; Mice ; Mice, Inbred C57BL ; Myometrium/immunology ; Ovalbumin/immunology ; Pregnancy ; Promoter Regions, Genetic ; Receptors, CXCR3/immunology/metabolism ; Stromal Cells/*immunology/*metabolism ; T-Lymphocyte Subsets/*immunology
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alberts, Bruce -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1521. doi: 10.1126/science.336.6088.1521.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723406" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Biomedical Research ; Disease Models, Animal ; *Ferrets ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/*pathogenicity ; Influenza, Human/transmission/*virology ; Orthomyxoviridae Infections/transmission/*virology ; *Publishing
    Print ISSN: 0036-8075
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  • 72
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hvistendahl, Mara -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):390. doi: 10.1126/science.335.6067.390.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282781" target="_blank"〉PubMed〈/a〉
    Keywords: China/epidemiology ; Female ; Homosexuality, Male/statistics & numerical data ; Humans ; Male ; Population Surveillance ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology ; Sex Workers/statistics & numerical data ; Syphilis/diagnosis/*epidemiology/prevention & control/transmission
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  • 73
    Publication Date: 2012-01-28
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812248/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812248/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fouchier, Ron A M -- Garcia-Sastre, Adolfo -- Kawaoka, Yoshihiro -- Barclay, Wendy S -- Bouvier, Nicole M -- Brown, Ian H -- Capua, Ilaria -- Chen, Hualan -- Compans, Richard W -- Couch, Robert B -- Cox, Nancy J -- Doherty, Peter C -- Donis, Ruben O -- Feldmann, Heinz -- Guan, Yi -- Katz, Jaqueline -- Klenk, H D -- Kobinger, Gary -- Liu, Jinhua -- Liu, Xiufan -- Lowen, Anice -- Mettenleiter, Thomas C -- Osterhaus, Albert D M E -- Palese, Peter -- Peiris, J S Malik -- Perez, Daniel R -- Richt, Jurgen A -- Schultz-Cherry, Stacey -- Steel, John -- Subbarao, Kanta -- Swayne, David E -- Takimoto, Toru -- Tashiro, Masato -- Taubenberger, Jeffery K -- Thomas, Paul G -- Tripp, Ralph A -- Tumpey, Terrence M -- Webby, Richard J -- Webster, Robert G -- Z01 AI000986-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):400-1. doi: 10.1126/science.335.6067.400.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282787" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomedical Research ; Disease Models, Animal ; Ferrets ; Humans ; *Influenza A Virus, H5N1 Subtype/pathogenicity ; Influenza, Human/transmission/virology ; Orthomyxoviridae Infections/*transmission/virology
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2012 Jul 13;337(6091):174-5. doi: 10.1126/science.337.6091.174.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22798597" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*epidemiology ; African Americans ; Anti-HIV Agents/therapeutic use ; *Epidemics ; Female ; Georgia/epidemiology ; HIV Infections/drug therapy/*epidemiology/prevention & control ; Homosexuality, Male ; *Hospitals, Public/statistics & numerical data ; Humans ; Male ; Outpatient Clinics, Hospital ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2012 Mar 9;335(6073):1155-6. doi: 10.1126/science.335.6073.1155.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22403358" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Containment of Biohazards ; Disease Models, Animal ; Ferrets ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/*pathogenicity ; Influenza, Human/epidemiology/transmission/*virology ; Mutation ; Orthomyxoviridae Infections/transmission/*virology ; Pandemics ; Publishing
    Print ISSN: 0036-8075
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  • 76
    Publication Date: 2012-09-18
    Description: The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted heterosynaptic competition and perturbed metabotropic glutamate receptor-dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the possibility of reverting neuronal circuit alterations in autism after the completion of development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baudouin, Stephane J -- Gaudias, Julien -- Gerharz, Stefan -- Hatstatt, Laetitia -- Zhou, Kuikui -- Punnakkal, Pradeep -- Tanaka, Kenji F -- Spooren, Will -- Hen, Rene -- De Zeeuw, Chris I -- Vogt, Kaspar -- Scheiffele, Peter -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):128-32. doi: 10.1126/science.1224159. Epub 2012 Sep 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biozentrum of the University of Basel, Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22983708" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*physiopathology ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; Disease Models, Animal ; Fragile X Syndrome/genetics/*physiopathology ; Male ; Membrane Proteins/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Net/metabolism/physiopathology/ultrastructure ; Nerve Tissue Proteins/genetics/metabolism ; *Neuronal Plasticity ; Synapses/metabolism/*physiology/ultrastructure
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  • 77
    Publication Date: 2012-11-01
    Description: The diseases of myelin are among the most prevalent and disabling conditions in neurology. These diseases include both the vascular and inflammatory demyelinating disorders of adulthood, as well as the childhood leukodystrophies and cerebral palsy. These fundamentally glial disorders may be amenable to treatment by glial progenitor cells (GPCs), which give rise to astroglia and myelin-producing oligodendrocytes. Given the development of new methods for generating and isolating human GPCs, the myelin disorders may now be compelling targets for cell-based therapy. In addition, the efficient engraftment and expansion of human GPCs in murine hosts has led to the development of human glial chimeric mouse brains, which provides new opportunities for studying the species-specific roles of human glia in cognition, as well as in disease pathogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548656/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548656/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldman, Steven A -- Nedergaard, Maiken -- Windrem, Martha S -- R01 NS075177/NS/NINDS NIH HHS/ -- R01 NS075345/NS/NINDS NIH HHS/ -- R01 NS078167/NS/NINDS NIH HHS/ -- R01 NS078304/NS/NINDS NIH HHS/ -- R01NS39559/NS/NINDS NIH HHS/ -- R01NS75345/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2012 Oct 26;338(6106):491-5. doi: 10.1126/science.1218071.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA. steven_goldman@urmc.rochester.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23112326" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Child ; Chimera ; Demyelinating Diseases/*therapy ; Disease Models, Animal ; Embryonic Stem Cells/cytology/physiology ; Humans ; Mice ; *Models, Neurological ; Myelin Sheath/metabolism ; Neural Stem Cells/physiology/*transplantation ; Oligodendroglia/metabolism/physiology/*transplantation
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  • 78
    Publication Date: 2013-08-31
    Description: The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However, the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that expression of the beta form of calcium/calmodulin-dependent protein kinase type II (betaCaMKappaIotaIota) was significantly up-regulated in the LHb of animal models of depression and down-regulated by antidepressants. Increasing beta-, but not alpha-, CaMKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons and was sufficient to produce profound depressive symptoms, including anhedonia and behavioral despair. Down-regulation of betaCaMKII levels, blocking its activity or its target molecule the glutamate receptor GluR1 reversed the depressive symptoms. These results identify betaCaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932364/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932364/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Kun -- Zhou, Tao -- Liao, Lujian -- Yang, Zhongfei -- Wong, Catherine -- Henn, Fritz -- Malinow, Roberto -- Yates, John R 3rd -- Hu, Hailan -- P41 GM103533/GM/NIGMS NIH HHS/ -- R01 MH067880/MH/NIMH NIH HHS/ -- R01 MH091119/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1016-20. doi: 10.1126/science.1240729.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P R China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & ; inhibitors/*biosynthesis/genetics ; Depressive Disorder, Major/*enzymology/genetics/psychology ; Disease Models, Animal ; Gene Knockdown Techniques ; Habenula/drug effects/*enzymology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/enzymology ; Promoter Regions, Genetic ; Proteomics ; Rats ; Rats, Sprague-Dawley
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  • 79
    Publication Date: 2013-11-16
    Description: Mitochondrial dysfunction contributes to numerous health problems, including neurological and muscular degeneration, cardiomyopathies, cancer, diabetes, and pathologies of aging. Severe mitochondrial defects can result in childhood disorders such as Leigh syndrome, for which there are no effective therapies. We found that rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055856/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055856/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Simon C -- Yanos, Melana E -- Kayser, Ernst-Bernhard -- Quintana, Albert -- Sangesland, Maya -- Castanza, Anthony -- Uhde, Lauren -- Hui, Jessica -- Wall, Valerie Z -- Gagnidze, Arni -- Oh, Kelly -- Wasko, Brian M -- Ramos, Fresnida J -- Palmiter, Richard D -- Rabinovitch, Peter S -- Morgan, Philip G -- Sedensky, Margaret M -- Kaeberlein, Matt -- R01 AG039390/AG/NIA NIH HHS/ -- T32 AG000057/AG/NIA NIH HHS/ -- T32 ES007032/ES/NIEHS NIH HHS/ -- T32AG000057/AG/NIA NIH HHS/ -- T32ES007032/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1524-8. doi: 10.1126/science.1244360. Epub 2013 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24231806" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/drug effects/enzymology/pathology ; Disease Models, Animal ; Electron Transport Complex I/genetics/metabolism ; Glycolysis/drug effects ; Leigh Disease/*drug therapy/genetics/pathology ; Mice ; Mice, Knockout ; Mice, Mutant Strains ; Mitochondria/drug effects/enzymology ; Mitochondrial Diseases/*drug therapy/genetics/pathology ; *Molecular Targeted Therapy ; Multiprotein Complexes/*antagonists & inhibitors ; Neuroprotective Agents/*therapeutic use ; Sirolimus/*therapeutic use ; TOR Serine-Threonine Kinases/*antagonists & inhibitors
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-10
    Description: During embryonic development, many cells are born far from their final destination and must travel long distances. To become motile and invasive, embryonic epithelial cells undergo a process of mesenchymal conversion known as epithelial-to-mesenchymal transition (EMT). Likewise, EMT can be seen in cancer cells as they leave the primary tumor and disseminate to other parts of the body to colonize distant organs and form metastases. In addition, through the reverse process (mesenchymal-to-epithelial transition), both normal and carcinoma cells revert to the epithelial phenotype to, respectively, differentiate into organs or form secondary tumors. The parallels in phenotypic plasticity in normal morphogenesis and cancer highlight the importance of studying the embryo to understand tumor progression and to aid in the design of improved therapeutic strategies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nieto, M Angela -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):1234850. doi: 10.1126/science.1234850.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Neurociencias Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad Miguel Hernandez (UMH), Avenida Ramon y Cajal s/n, 03550 San Juan de Alicante, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24202173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma/*pathology ; Cell Movement ; Disease Models, Animal ; Embryonic Stem Cells/*physiology ; *Epithelial-Mesenchymal Transition ; Humans ; Mice ; Neoplasms/drug therapy/*pathology ; Neoplastic Stem Cells/drug effects/*physiology
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  • 81
    Publication Date: 2013-01-19
    Description: Environmental stressors during childhood and adolescence influence postnatal brain maturation and human behavioral patterns in adulthood. Accordingly, excess stressors result in adult-onset neuropsychiatric disorders. We describe an underlying mechanism in which glucocorticoids link adolescent stressors to epigenetic controls in neurons. In a mouse model of this phenomenon, a mild isolation stress affects the mesocortical projection of dopaminergic neurons in which DNA hypermethylation of the tyrosine hydroxylase gene is elicited, but only when combined with a relevant genetic risk for neuropsychiatric disorders. These molecular changes are associated with several neurochemical and behavioral deficits that occur in this mouse model, all of which are blocked by a glucocorticoid receptor antagonist. The biology and phenotypes of the mouse models resemble those of psychotic depression, a common and debilitating psychiatric disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617477/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617477/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Niwa, Minae -- Jaaro-Peled, Hanna -- Tankou, Stephanie -- Seshadri, Saurav -- Hikida, Takatoshi -- Matsumoto, Yurie -- Cascella, Nicola G -- Kano, Shin-ichi -- Ozaki, Norio -- Nabeshima, Toshitaka -- Sawa, Akira -- K99 MH094408/MH/NIMH NIH HHS/ -- K99MH-094408/MH/NIMH NIH HHS/ -- MH-069853/MH/NIMH NIH HHS/ -- MH-084018/MH/NIMH NIH HHS/ -- MH-085226/MH/NIMH NIH HHS/ -- MH-088753/MH/NIMH NIH HHS/ -- MH-092443/MH/NIMH NIH HHS/ -- MH-094268/MH/NIMH NIH HHS/ -- R01 MH092443/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 18;339(6117):335-9. doi: 10.1126/science.1226931.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23329051" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; *Adolescent Behavior ; *Adolescent Development ; Affective Disorders, Psychotic/genetics/*metabolism ; Animals ; Disease Models, Animal ; Dopaminergic Neurons/*metabolism ; *Epigenesis, Genetic ; Glucocorticoids/*metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Tissue Proteins/genetics/metabolism ; Stress, Psychological/genetics/*metabolism
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  • 82
    Publication Date: 2013-06-08
    Description: Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin-based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem cells derived from the intestine can be cultured to build epithelial structures that retain hallmarks of the in vivo epithelium. Here, we review the mechanisms that support this notable example of self-organization and discuss applications of this technology for stem cell research, disease modeling (e.g., for colorectal cancer and cystic fibrosis), and regenerative medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, Toshiro -- Clevers, Hans -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1190-4. doi: 10.1126/science.1234852.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan. t.sato@a7.keio.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744940" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*physiology ; Animals ; Cell Count ; *Cell Culture Techniques ; Disease Models, Animal ; Ephrin-B1/metabolism ; Humans ; Intestinal Mucosa/physiology ; Intestine, Small/*growth & development ; Mice ; *Morphogenesis ; Receptors, G-Protein-Coupled/genetics ; *Regenerative Medicine ; Stem Cell Niche ; Wnt Proteins/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 83
    Publication Date: 2013-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Eliot -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):680. doi: 10.1126/science.342.6159.680.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24202151" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/blood ; Down Syndrome/*diagnosis ; Female ; Genetic Testing/*legislation & jurisprudence ; Humans ; Intellectual Property ; Male ; Patents as Topic/*legislation & jurisprudence ; Pregnancy ; Prenatal Diagnosis/*methods ; San Francisco
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-08-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):833-6. doi: 10.1126/science.341.6148.833.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23970676" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspase 9/genetics/*metabolism ; DNA, Bacterial/*genetics ; Disease Models, Animal ; Food Microbiology ; Gene Knockout Techniques/methods ; Gene Targeting/*methods ; Genome/genetics ; Humans ; Mice ; Rats ; *Streptococcus Phages ; Streptococcus thermophilus/*genetics/*immunology/virology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 85
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-03-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2013 Mar 8;339(6124):1134. doi: 10.1126/science.339.6124.1134.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23471378" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/*therapeutic use ; *Convalescence ; *Early Medical Intervention ; Female ; HIV/isolation & purification ; HIV Infections/*blood/*drug therapy/transmission ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/prevention & control ; Pregnancy ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 86
    Publication Date: 2013-03-02
    Description: Human birth defects are a major public health burden: The Center for Disease Control estimates that 1 of every 33 United States newborns presents with a birth defect, and worldwide the estimate approaches 6% of all births. Among the most common and debilitating of human birth defects are those affecting the formation of the neural tube, the precursor to the central nervous system. Neural tube defects (NTDs) arise from a complex combination of genetic and environmental interactions. Although substantial advances have been made in the prevention and treatment of these malformations, NTDs remain a substantial public health problem, and we are only now beginning to understand their etiology. Here, we review the process of neural tube development and how defects in this process lead to NTDs, both in humans and in the animal models that serve to inform our understanding of these processes. The insights we are gaining will help generate new intervention strategies to tackle the clinical challenges and to alleviate the personal and societal burdens that accompany these defects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677196/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677196/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wallingford, John B -- Niswander, Lee A -- Shaw, Gary M -- Finnell, Richard H -- 5R01GM074104/GM/NIGMS NIH HHS/ -- P01 HD067244/HD/NICHD NIH HHS/ -- P01HD067244/HD/NICHD NIH HHS/ -- R01 GM074104/GM/NIGMS NIH HHS/ -- R01NS050249/NS/NINDS NIH HHS/ -- R01NS058979/NS/NINDS NIH HHS/ -- R01NS076465/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1222002. doi: 10.1126/science.1222002.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, The University of Texas at Austin, Austin, TX 78712, USA. wallingford@austin.utexas.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23449594" target="_blank"〉PubMed〈/a〉
    Keywords: Amphibians/abnormalities ; Animals ; Disease Models, Animal ; Embryo, Nonmammalian/abnormalities ; Folic Acid/administration & dosage/metabolism ; Folic Acid Deficiency/complications/genetics ; Humans ; Mutation ; Neural Tube Defects/*genetics/*prevention & control/therapy ; Primary Prevention
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  • 87
    Publication Date: 2013-02-09
    Description: To discover interordinal relationships of living and fossil placental mammals and the time of origin of placentals relative to the Cretaceous-Paleogene (K-Pg) boundary, we scored 4541 phenomic characters de novo for 86 fossil and living species. Combining these data with molecular sequences, we obtained a phylogenetic tree that, when calibrated with fossils, shows that crown clade Placentalia and placental orders originated after the K-Pg boundary. Many nodes discovered using molecular data are upheld, but phenomic signals overturn molecular signals to show Sundatheria (Dermoptera + Scandentia) as the sister taxon of Primates, a close link between Proboscidea (elephants) and Sirenia (sea cows), and the monophyly of echolocating Chiroptera (bats). Our tree suggests that Placentalia first split into Xenarthra and Epitheria; extinct New World species are the oldest members of Afrotheria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Leary, Maureen A -- Bloch, Jonathan I -- Flynn, John J -- Gaudin, Timothy J -- Giallombardo, Andres -- Giannini, Norberto P -- Goldberg, Suzann L -- Kraatz, Brian P -- Luo, Zhe-Xi -- Meng, Jin -- Ni, Xijun -- Novacek, Michael J -- Perini, Fernando A -- Randall, Zachary S -- Rougier, Guillermo W -- Sargis, Eric J -- Silcox, Mary T -- Simmons, Nancy B -- Spaulding, Michelle -- Velazco, Paul M -- Weksler, Marcelo -- Wible, John R -- Cirranello, Andrea L -- New York, N.Y. -- Science. 2013 Feb 8;339(6120):662-7. doi: 10.1126/science.1229237.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomical Sciences, School of Medicine, HSC T-8 (040), Stony Brook University, Stony Brook, NY 11794-8081, USA. maureen.oleary@stonybrook.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Biological Evolution ; Dentition ; Ecosystem ; Extinction, Biological ; Female ; *Fossils ; *Mammals/anatomy & histology/classification/genetics ; Paleodontology ; *Phylogeny ; Phylogeography ; Placenta ; Pregnancy ; Sequence Alignment ; Time ; Xenarthra/anatomy & histology/classification/genetics
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  • 88
    Publication Date: 2013-09-21
    Description: Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced mu-opioid receptor (MOR) constitutive activity (MOR(CA)) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3',5'-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MOR(CA) initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MOR(CA) suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440417/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440417/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corder, G -- Doolen, S -- Donahue, R R -- Winter, M K -- Jutras, B L -- He, Y -- Hu, X -- Wieskopf, J S -- Mogil, J S -- Storm, D R -- Wang, Z J -- McCarson, K E -- Taylor, B K -- 5K02DA19656/DA/NIDA NIH HHS/ -- F31 DA032496/DA/NIDA NIH HHS/ -- F31DA032496/DA/NIDA NIH HHS/ -- HD02528/HD/NICHD NIH HHS/ -- K02 DA019656/DA/NIDA NIH HHS/ -- P30 HD002528/HD/NICHD NIH HHS/ -- R01 NS045954/NS/NINDS NIH HHS/ -- R01NS45954/NS/NINDS NIH HHS/ -- UL1 TR000117/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1394-9. doi: 10.1126/science.1239403.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24052307" target="_blank"〉PubMed〈/a〉
    Keywords: Acute Pain/metabolism ; Adenosine Monophosphate/metabolism ; Adenylyl Cyclases/metabolism ; Animals ; Chronic Pain/*metabolism ; Disease Models, Animal ; Freund's Adjuvant/pharmacology ; Hyperalgesia/chemically induced/*metabolism ; Isoflurane/pharmacology ; Male ; Mice ; Naltrexone/analogs & derivatives/pharmacology ; Nociceptive Pain/*metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Receptors, Opioid, mu/agonists/antagonists & inhibitors/*metabolism ; Spinal Cord/drug effects/metabolism ; Substance Withdrawal Syndrome/metabolism
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  • 89
    Publication Date: 2013-09-21
    Description: Soluble beta-amyloid (Abeta) oligomers impair synaptic plasticity and cause synaptic loss associated with Alzheimer's disease (AD). We report that murine PirB (paired immunoglobulin-like receptor B) and its human ortholog LilrB2 (leukocyte immunoglobulin-like receptor B2), present in human brain, are receptors for Abeta oligomers, with nanomolar affinity. The first two extracellular immunoglobulin (Ig) domains of PirB and LilrB2 mediate this interaction, leading to enhanced cofilin signaling, also seen in human AD brains. In mice, the deleterious effect of Abeta oligomers on hippocampal long-term potentiation required PirB, and in a transgenic model of AD, PirB not only contributed to memory deficits present in adult mice, but also mediated loss of synaptic plasticity in juvenile visual cortex. These findings imply that LilrB2 contributes to human AD neuropathology and suggest therapeutic uses of blocking LilrB2 function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853120/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853120/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Taeho -- Vidal, George S -- Djurisic, Maja -- William, Christopher M -- Birnbaum, Michael E -- Garcia, K Christopher -- Hyman, Bradley T -- Shatz, Carla J -- 5P50AG005134/AG/NIA NIH HHS/ -- 5R01AG041507/AG/NIA NIH HHS/ -- 5T32EY020485/EY/NEI NIH HHS/ -- EY02858/EY/NEI NIH HHS/ -- K08 NS069811/NS/NINDS NIH HHS/ -- K08NS069811/NS/NINDS NIH HHS/ -- NS069375/NS/NINDS NIH HHS/ -- R01 AG041507/AG/NIA NIH HHS/ -- R01 EY002858/EY/NEI NIH HHS/ -- R01 MH071666/MH/NIMH NIH HHS/ -- T32 EY020485/EY/NEI NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1399-404. doi: 10.1126/science.1242077.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA. tkim808@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24052308" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*physiopathology ; Amyloid beta-Peptides/*metabolism/pharmacology ; Animals ; Disease Models, Animal ; Female ; HEK293 Cells ; Hippocampus/physiopathology ; Humans ; Long-Term Potentiation ; Male ; Membrane Glycoproteins/genetics/*physiology ; Mice ; Mice, Transgenic ; *Neuronal Plasticity ; Peptide Fragments/*metabolism/pharmacology ; Receptors, Immunologic/genetics/*physiology ; Synapses/*physiology
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  • 90
    Publication Date: 2013-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1160-1. doi: 10.1126/science.340.6137.1160.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744922" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Birth Weight ; Body Composition ; Diet ; Female ; *Fetal Development ; *Health ; Heart Diseases/epidemiology ; Humans ; Infant, Low Birth Weight/growth & development ; Infant, Newborn ; Insulin Resistance ; Male ; Maternal Nutritional Physiological Phenomena ; Placenta/*anatomy & histology ; Pregnancy ; Uterus/*metabolism
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  • 91
    Publication Date: 2013-06-01
    Description: Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, tuberculosis, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances toward vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively generating vaccine-induced protective immune responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026248/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026248/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koff, Wayne C -- Burton, Dennis R -- Johnson, Philip R -- Walker, Bruce D -- King, Charles R -- Nabel, Gary J -- Ahmed, Rafi -- Bhan, Maharaj K -- Plotkin, Stanley A -- UM1 AI100663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1232910. doi: 10.1126/science.1232910.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA. wkoff@iavi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723240" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/prevention & control ; Adjuvants, Immunologic/administration & dosage ; Animals ; Antigens/genetics/immunology/isolation & purification ; *Communicable Disease Control ; Disease Models, Animal ; Drug Delivery Systems ; Humans ; Malaria/prevention & control ; Tuberculosis/prevention & control ; Vaccines/administration & dosage/*immunology
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  • 92
    Publication Date: 2013-05-21
    Description: Several progeroid disorders, including Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (ZMPSTE24 deficiency), arise when a farnesylated and methylated form of prelamin A accumulates at the nuclear envelope. Here, we found that a hypomorphic allele of isoprenylcysteine carboxyl methyltransferase (ICMT) increased body weight, normalized grip strength, and prevented bone fractures and death in Zmpste24-deficient mice. The reduced ICMT activity caused prelamin A mislocalization within the nucleus and triggered prelamin A-dependent activation of AKT-mammalian target of rapamycin (mTOR) signaling, which abolished the premature senescence of Zmpste24-deficient fibroblasts. ICMT inhibition increased AKT-mTOR signaling and proliferation and delayed senescence in human HGPS fibroblasts but did not reduce the levels of misshapen nuclei in mouse and human cells. Thus, targeting ICMT might be useful for treating prelamin A-associated progeroid disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295631/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295631/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ibrahim, Mohamed X -- Sayin, Volkan I -- Akula, Murali K -- Liu, Meng -- Fong, Loren G -- Young, Stephen G -- Bergo, Martin O -- P01 HL090553/HL/NHLBI NIH HHS/ -- R01 AG035626/AG/NIA NIH HHS/ -- R01 HL086683/HL/NHLBI NIH HHS/ -- R01 HL089781/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 14;340(6138):1330-3. doi: 10.1126/science.1238880. Epub 2013 May 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, S-41390 Gothenburg, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23686339" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Aging/genetics ; Cell Nucleus/metabolism ; Disease Models, Animal ; Fibroblasts/metabolism ; *Gene Knockout Techniques ; Hand Strength ; Humans ; Lamin Type A ; Membrane Proteins/genetics/*metabolism ; Metalloendopeptidases/genetics/*metabolism ; Methylation ; Mice ; Mice, Mutant Strains ; Nuclear Proteins/metabolism ; Progeria/physiopathology/*therapy ; Protein Methyltransferases/*genetics/*metabolism ; Protein Precursors/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Weight Gain/genetics
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  • 93
    Publication Date: 2013-06-08
    Description: Dysfunctions in frontostriatal brain circuits have been implicated in neuropsychiatric disorders, including those characterized by the presence of repetitive behaviors. We developed an optogenetic approach to block repetitive, compulsive behavior in a mouse model in which deletion of the synaptic scaffolding gene, Sapap3, results in excessive grooming. With a delay-conditioning task, we identified in the mutants a selective deficit in behavioral response inhibition and found this to be associated with defective down-regulation of striatal projection neuron activity. Focused optogenetic stimulation of the lateral orbitofrontal cortex and its terminals in the striatum restored the behavioral response inhibition, restored the defective down-regulation, and compensated for impaired fast-spiking neuron striatal microcircuits. These findings raise promising potential for the design of targeted therapy for disorders involving excessive repetitive behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876800/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876800/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burguiere, Eric -- Monteiro, Patricia -- Feng, Guoping -- Graybiel, Ann M -- R01 HD028341/HD/NICHD NIH HHS/ -- R01 MH081201/MH/NIMH NIH HHS/ -- R01 MH097104/MH/NIMH NIH HHS/ -- R37 HD028341/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1243-6. doi: 10.1126/science.1232380.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744950" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Compulsive Behavior/*therapy ; Corpus Striatum/*physiopathology ; Disease Models, Animal ; Frontal Lobe/*physiopathology ; Gene Deletion ; Gene Targeting ; Grooming ; Male ; Mice ; Nerve Tissue Proteins/*genetics ; Neurons/physiology ; Optogenetics/*methods
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-07-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitehead, Nadia -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):249. doi: 10.1126/science.345.6194.249.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035466" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*urine ; Congo Red ; Female ; Humans ; Pre-Eclampsia/*diagnosis/metabolism/urine ; Pregnancy ; *Protein Folding ; Proteostasis Deficiencies/*diagnosis/metabolism/urine ; Urinalysis/*methods
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  • 95
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-06-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1073. doi: 10.1126/science.344.6188.1073.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904134" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*trends ; Female ; Fetal Development ; Fetus/blood supply ; Humans ; *Placenta/blood supply/physiopathology ; Placentation ; Pregnancy ; Umbilical Cord/physiology
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  • 96
    Publication Date: 2014-06-07
    Description: Auditory hallucinations in schizophrenia are alleviated by antipsychotic agents that inhibit D2 dopamine receptors (Drd2s). The defective neural circuits and mechanisms of their sensitivity to antipsychotics are unknown. We identified a specific disruption of synaptic transmission at thalamocortical glutamatergic projections in the auditory cortex in murine models of schizophrenia-associated 22q11 deletion syndrome (22q11DS). This deficit is caused by an aberrant elevation of Drd2 in the thalamus, which renders 22q11DS thalamocortical projections sensitive to antipsychotics and causes a deficient acoustic startle response similar to that observed in schizophrenic patients. Haploinsufficiency of the microRNA-processing gene Dgcr8 is responsible for the Drd2 elevation and hypersensitivity of auditory thalamocortical projections to antipsychotics. This suggests that Dgcr8-microRNA-Drd2-dependent thalamocortical disruption is a pathogenic event underlying schizophrenia-associated psychosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349506/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349506/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chun, Sungkun -- Westmoreland, Joby J -- Bayazitov, Ildar T -- Eddins, Donnie -- Pani, Amar K -- Smeyne, Richard J -- Yu, Jing -- Blundon, Jay A -- Zakharenko, Stanislav S -- R01 DC012833/DC/NIDCD NIH HHS/ -- R01 MH095810/MH/NIMH NIH HHS/ -- R01 MH097742/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1178-82. doi: 10.1126/science.1253895.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. ; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. stanislav.zakharenko@stjude.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904170" target="_blank"〉PubMed〈/a〉
    Keywords: 22q11 Deletion Syndrome/drug therapy/*genetics ; Animals ; Antipsychotic Agents/therapeutic use ; Auditory Cortex/*metabolism ; Disease Models, Animal ; Drug Resistance/genetics ; *Haploinsufficiency ; Mice ; Mice, Mutant Strains ; MicroRNAs/metabolism ; RNA-Binding Proteins/*genetics ; Receptors, Dopamine D2/*biosynthesis/genetics ; Schizophrenia/drug therapy/*genetics ; Synaptic Transmission/genetics ; Thalamus/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Portella, Andre Krumel -- Silveira, Patricia Pelufo -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1571-2. doi: 10.1126/science.345.6204.1571-c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Universidade Federal de Ciencias Medicas de Porto Alegre, 90050-170, Brazil. ; Department of Pediatrics, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2350, 90035-903, Porto Alegre, RS, Brazil. 00032386@ufrgs.br.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25258072" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fetus/*physiology ; *Food Preferences ; Humans ; Infant, Newborn/*physiology ; *Mothers ; Pregnancy ; *Taste
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2014-02-22
    Description: Growth factors (GFs) are critical in tissue repair, but their translation to clinical use has been modest. Physiologically, GF interactions with extracellular matrix (ECM) components facilitate localized and spatially regulated signaling; therefore, we reasoned that the lack of ECM binding in their clinically used forms could underlie the limited translation. We discovered that a domain in placenta growth factor-2 (PlGF-2(123-144)) binds exceptionally strongly and promiscuously to ECM proteins. By fusing this domain to the GFs vascular endothelial growth factor-A, platelet-derived growth factor-BB, and bone morphogenetic protein-2, we generated engineered GF variants with super-affinity to the ECM. These ECM super-affinity GFs induced repair in rodent models of chronic wounds and bone defects that was greatly enhanced as compared to treatment with the wild-type GFs, demonstrating that this approach may be useful in several regenerative medicine applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martino, Mikael M -- Briquez, Priscilla S -- Guc, Esra -- Tortelli, Federico -- Kilarski, Witold W -- Metzger, Stephanie -- Rice, Jeffrey J -- Kuhn, Gisela A -- Muller, Ralph -- Swartz, Melody A -- Hubbell, Jeffrey A -- New York, N.Y. -- Science. 2014 Feb 21;343(6173):885-8. doi: 10.1126/science.1247663.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24558160" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Protein 2/chemistry/genetics/metabolism ; Disease Models, Animal ; Extracellular Matrix/*metabolism ; Extracellular Matrix Proteins/chemistry/metabolism ; Heparitin Sulfate/chemistry/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pregnancy Proteins/chemistry/genetics/metabolism ; Protein Engineering ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-sis/chemistry/genetics/metabolism ; Vascular Endothelial Growth Factor A/chemistry/genetics/metabolism ; *Wound Healing
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2014-07-12
    Description: Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, which may have an impact on F2 development. Differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404520/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404520/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Radford, Elizabeth J -- Ito, Mitsuteru -- Shi, Hui -- Corish, Jennifer A -- Yamazawa, Kazuki -- Isganaitis, Elvira -- Seisenberger, Stefanie -- Hore, Timothy A -- Reik, Wolf -- Erkek, Serap -- Peters, Antoine H F M -- Patti, Mary-Elizabeth -- Ferguson-Smith, Anne C -- 095606/Wellcome Trust/United Kingdom -- 095645/Wellcome Trust/United Kingdom -- P30 DK036836/DK/NIDDK NIH HHS/ -- P30DK036836/DK/NIDDK NIH HHS/ -- R00 HD064793/HD/NICHD NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):1255903. doi: 10.1126/science.1255903. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. ; Research Division, Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA. ; The Babraham Institute, Babraham, Cambridge, and Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. ; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. Swiss Institute of Bioinformatics, Basel, Switzerland. ; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. Faculty of Sciences, University of Basel, Basel, Switzerland. ; Research Division, Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA. afsmith@mole.bio.cam.ac.uk mary.elizabeth.patti@joslin.harvard.edu. ; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. afsmith@mole.bio.cam.ac.uk mary.elizabeth.patti@joslin.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25011554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caloric Restriction ; *DNA Methylation ; Epigenesis, Genetic ; Female ; Fetal Nutrition Disorders/genetics/*metabolism ; Insulin/secretion ; Male ; Metabolic Diseases/metabolism ; Mice ; Mice, Inbred ICR ; Nucleosomes/metabolism ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Spermatozoa/*metabolism/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-16
    Description: At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte cytosine methylation and chromatin patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic effects interact with conditions at conception to program the developmental trajectory of the embryo and fetus, ultimately affecting the lifetime health of the child. These insights compel us to revise generally held notions to accommodate the prospect that biological parenting commences well before birth, even prior to conception.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lane, Michelle -- Robker, Rebecca L -- Robertson, Sarah A -- New York, N.Y. -- Science. 2014 Aug 15;345(6198):756-60. doi: 10.1126/science.1254400. Epub 2014 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Robinson Research Institute and School of Paediatrics and Reproductive Health, The University of Adelaide, Level 3, Medical School, South Adelaide, SA, 5005 Australia. ; The Robinson Research Institute and School of Paediatrics and Reproductive Health, The University of Adelaide, Level 3, Medical School, South Adelaide, SA, 5005 Australia. sarah.robertson@adelaide.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25124428" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryo, Mammalian/*physiology ; Embryonic Development ; *Epigenesis, Genetic ; *Fathers ; Female ; *Fertilization ; Humans ; Male ; Maternal Nutritional Physiological Phenomena ; *Mothers ; Oocytes/physiology ; Pregnancy ; Prenatal Exposure Delayed Effects ; RNA, Untranslated/metabolism ; Semen/physiology ; Spermatozoa/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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