ALBERT

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1188-90. doi: 10.1126/science.350.6265.1188.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785475" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Servick, Kelly -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):15. doi: 10.1126/science.351.6268.15.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721984" target="_blank"〉PubMed〈/a〉

Description: Voltage-gated CaV1.2 channels (L-type calcium channel alpha1C subunits) are critical mediators of transcription-dependent neural plasticity. Whether these channels signal via the influx of calcium ion (Ca(2+)), voltage-dependent conformational change (VDeltaC), or a combination of the two has thus far been equivocal. We fused CaV1.2 to a ligand-gated Ca(2+)-permeable channel, enabling independent control of localized Ca(2+) and VDeltaC signals. This revealed an unexpected dual requirement: Ca(2+) must first mobilize actin-bound Ca(2+)/calmodulin-dependent protein kinase II, freeing it for subsequent VDeltaC-mediated accumulation. Neither signal alone sufficed to activate transcription. Signal order was crucial: Efficiency peaked when Ca(2+) preceded VDeltaC by 10 to 20 seconds. CaV1.2 VDeltaC synergistically augmented signaling by N-methyl-d-aspartate receptors. Furthermore, VDeltaC mistuning correlated with autistic symptoms in Timothy syndrome. Thus, nonionic VDeltaC signaling is vital to the function of CaV1.2 in synaptic and neuropsychiatric processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Boxing -- Tadross, Michael R -- Tsien, Richard W -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):863-7. doi: 10.1126/science.aad3647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA. ; Department of Molecular and Cellular Physiology, Beckman Center, School of Medicine, Stanford University, Stanford, CA 94305, USA. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. tadrossm@janelia.hhmi.org. ; Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA. Department of Molecular and Cellular Physiology, Beckman Center, School of Medicine, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912895" target="_blank"〉PubMed〈/a〉

Description: To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tirosh, Itay -- Izar, Benjamin -- Prakadan, Sanjay M -- Wadsworth, Marc H 2nd -- Treacy, Daniel -- Trombetta, John J -- Rotem, Asaf -- Rodman, Christopher -- Lian, Christine -- Murphy, George -- Fallahi-Sichani, Mohammad -- Dutton-Regester, Ken -- Lin, Jia-Ren -- Cohen, Ofir -- Shah, Parin -- Lu, Diana -- Genshaft, Alex S -- Hughes, Travis K -- Ziegler, Carly G K -- Kazer, Samuel W -- Gaillard, Aleth -- Kolb, Kellie E -- Villani, Alexandra-Chloe -- Johannessen, Cory M -- Andreev, Aleksandr Y -- Van Allen, Eliezer M -- Bertagnolli, Monica -- Sorger, Peter K -- Sullivan, Ryan J -- Flaherty, Keith T -- Frederick, Dennie T -- Jane-Valbuena, Judit -- Yoon, Charles H -- Rozenblatt-Rosen, Orit -- Shalek, Alex K -- Regev, Aviv -- Garraway, Levi A -- 1U24CA180922/CA/NCI NIH HHS/ -- DP2 OD020839/OD/NIH HHS/ -- K99 CA194163/CA/NCI NIH HHS/ -- K99CA194163/CA/NCI NIH HHS/ -- P01CA163222/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- P50GM107618/GM/NIGMS NIH HHS/ -- R35CA197737/CA/NCI NIH HHS/ -- U54CA112962/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):189-96. doi: 10.1126/science.aad0501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. ; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. ; HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Surgical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Department of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Program in Therapeutic Sciences, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. HMS LINCS Center and Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Ludwig Center at Harvard, Boston, MA 02215, USA. ; Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02142, USA. Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA 02139, USA. Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Department of Immunology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Biology and Koch Institute, MIT, Boston, MA 02142, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. bizar@partners.org aregev@broadinstitute.org levi_garraway@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124452" target="_blank"〉PubMed〈/a〉

Description: Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772156/" 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/PMC4772156/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferenczi, Emily A -- Zalocusky, Kelly A -- Liston, Conor -- Grosenick, Logan -- Warden, Melissa R -- Amatya, Debha -- Katovich, Kiefer -- Mehta, Hershel -- Patenaude, Brian -- Ramakrishnan, Charu -- Kalanithi, Paul -- Etkin, Amit -- Knutson, Brian -- Glover, Gary H -- Deisseroth, Karl -- 1F31MH105151_01/MH/NIMH NIH HHS/ -- P41 EB015891/EB/NIBIB NIH HHS/ -- R00 MH097822/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Neurosciences Program, Stanford University, Stanford, CA 94305, USA. ; Brain Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. ; Department of Psychology, Stanford University, Stanford, CA 94305, USA. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. ; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA. ; Department of Radiology, Stanford University, Stanford, CA, 94305, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA. deissero@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26722001" target="_blank"〉PubMed〈/a〉

Description: Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme alpha/beta hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Melissa R -- Mannowetz, Nadja -- Iavarone, Anthony T -- Safavi, Rojin -- Gracheva, Elena O -- Smith, James F -- Hill, Rose Z -- Bautista, Diana M -- Kirichok, Yuriy -- Lishko, Polina V -- 1S10OD020062-01/OD/NIH HHS/ -- R01 AR059385/AR/NIAMS NIH HHS/ -- R01AR059385/AR/NIAMS NIH HHS/ -- R01GM111802/GM/NIGMS NIH HHS/ -- R01HD068914/HD/NICHD NIH HHS/ -- R21HD081403/HD/NICHD NIH HHS/ -- S10RR025622/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):555-9. doi: 10.1126/science.aad6887. Epub 2016 Mar 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; QB3/Chemistry Mass Spectrometry Facility, University of California, Berkeley, CA 94720, USA. ; Department of Cellular and Molecular Physiology; Department of Neuroscience, Program in Cellular Neuroscience, Neurodegeneration, and Repair (CNNR), Yale School of Medicine, Yale University, New Haven, CT 06536, USA. ; Department of Urology, University of California, San Francisco, CA 94143, USA. ; Department of Physiology, University of California, San Francisco, CA 94158, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. lishko@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989199" target="_blank"〉PubMed〈/a〉

Description: Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nielsen, Alec A K -- Der, Bryan S -- Shin, Jonghyeon -- Vaidyanathan, Prashant -- Paralanov, Vanya -- Strychalski, Elizabeth A -- Ross, David -- Densmore, Douglas -- Voigt, Christopher A -- P50 GM098792/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):aac7341. doi: 10.1126/science.aac7341.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA. ; Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA. ; Biosystems and Biomaterials Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20817, USA. ; Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cavoigt@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034378" target="_blank"〉PubMed〈/a〉

Description: Cell assembly sequences during learning are "replayed" during hippocampal ripples and contribute to the consolidation of episodic memories. However, neuronal sequences may also reflect preexisting dynamics. We report that sequences of place-cell firing in a novel environment are formed from a combination of the contributions of a rigid, predominantly fast-firing subset of pyramidal neurons with low spatial specificity and limited change across sleep-experience-sleep and a slow-firing plastic subset. Slow-firing cells, rather than fast-firing cells, gained high place specificity during exploration, elevated their association with ripples, and showed increased bursting and temporal coactivation during postexperience sleep. Thus, slow- and fast-firing neurons, although forming a continuous distribution, have different coding and plastic properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grosmark, Andres D -- Buzsaki, Gyorgy -- MH102840/MH/NIMH NIH HHS/ -- MH54671/MH/NIMH NIH HHS/ -- NS075015/NS/NINDS NIH HHS/ -- R01 MH107396/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1440-3. doi: 10.1126/science.aad1935.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University Medical Center, New York, NY 10019, USA. The Neuroscience Institute, School of Medicine, New York University, New York, NY 10016, USA. ; The Neuroscience Institute, School of Medicine, New York University, New York, NY 10016, USA. Center for Neural Science, New York University, New York, NY 10016, USA. gyorgy.buzsaki@nyumc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013730" target="_blank"〉PubMed〈/a〉

Description: Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression of C9orf72 is seen in expansion carriers, suggesting that loss of function may play a role in disease. We found that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease. Instead, C9orf72 null mice developed progressive splenomegaly and lymphadenopathy with accumulation of engorged macrophage-like cells. C9orf72 expression was highest in myeloid cells, and the loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 ALS but not sporadic ALS human patient tissue. Thus, C9orf72 is required for the normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in C9orf72 expansion carriers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Rourke, J G -- Bogdanik, L -- Yanez, A -- Lall, D -- Wolf, A J -- Muhammad, A K M G -- Ho, R -- Carmona, S -- Vit, J P -- Zarrow, J -- Kim, K J -- Bell, S -- Harms, M B -- Miller, T M -- Dangler, C A -- Underhill, D M -- Goodridge, H S -- Lutz, C M -- Baloh, R H -- GM085796/GM/NIGMS NIH HHS/ -- NS069669/NS/NINDS NIH HHS/ -- NS078398/NS/NINDS NIH HHS/ -- NS087351/NS/NINDS NIH HHS/ -- UL1TR000124/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1324-9. doi: 10.1126/science.aaf1064.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. ; The Jackson Laboratory, Bar Harbor, ME, USA. ; Division of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. ; Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. ; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. Department of Neurology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989253" target="_blank"〉PubMed〈/a〉

Description: Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825693/" 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/PMC4825693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrera, Luis A -- Vedenko, Anastasia -- Kurland, Jesse V -- Rogers, Julia M -- Gisselbrecht, Stephen S -- Rossin, Elizabeth J -- Woodard, Jaie -- Mariani, Luca -- Kock, Kian Hong -- Inukai, Sachi -- Siggers, Trevor -- Shokri, Leila -- Gordan, Raluca -- Sahni, Nidhi -- Cotsapas, Chris -- Hao, Tong -- Yi, Song -- Kellis, Manolis -- Daly, Mark J -- Vidal, Marc -- Hill, David E -- Bulyk, Martha L -- P50 HG004233/HG/NHGRI NIH HHS/ -- R01 HG003985/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1450-4. doi: 10.1126/science.aad2257. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. ; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA. ; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Center for Human Genetics Research and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA. Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013732" target="_blank"〉PubMed〈/a〉

Description: SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3-deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56beta, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2). Pharmacological and genetic activation of Akt or inhibition of CLK2 relieved synaptic deficits in Shank3-deficient and PMDS patient-derived neurons. CLK2 inhibition also restored normal sociability in a Shank3-deficient mouse model. Our study thereby provides a novel mechanistic and potentially therapeutic understanding of deregulated signaling downstream of Shank3 deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bidinosti, Michael -- Botta, Paolo -- Kruttner, Sebastian -- Proenca, Catia C -- Stoehr, Natacha -- Bernhard, Mario -- Fruh, Isabelle -- Mueller, Matthias -- Bonenfant, Debora -- Voshol, Hans -- Carbone, Walter -- Neal, Sarah J -- McTighe, Stephanie M -- Roma, Guglielmo -- Dolmetsch, Ricardo E -- Porter, Jeffrey A -- Caroni, Pico -- Bouwmeester, Tewis -- Luthi, Andreas -- Galimberti, Ivan -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1199-203. doi: 10.1126/science.aad5487. Epub 2016 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Friedrich Miescher Institute, Basel, Switzerland. ; Analytical Sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland. ; Neuroscience, Novartis Institutes for Biomedical Research, Cambridge, USA. ; Developmental Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland. ivan.galimberti@novartis.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26847545" target="_blank"〉PubMed〈/a〉

Description: The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational "detyrosination" of alpha-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres. When detyrosination was reduced, MTs uncoupled from sarcomeres and buckled less during contraction, which allowed sarcomeres to shorten and stretch with less resistance. Conversely, increased detyrosination promoted MT buckling, stiffened the myocyte, and correlated with impaired function in cardiomyopathy. Thus, detyrosinated MTs represent tunable, compression-resistant elements that may impair cardiac function in disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robison, Patrick -- Caporizzo, Matthew A -- Ahmadzadeh, Hossein -- Bogush, Alexey I -- Chen, Christina Yingxian -- Margulies, Kenneth B -- Shenoy, Vivek B -- Prosser, Benjamin L -- HL089847/HL/NHLBI NIH HHS/ -- HL105993/HL/NHLBI NIH HHS/ -- R00-HL114879/HL/NHLBI NIH HHS/ -- R01EB017753/EB/NIBIB NIH HHS/ -- T32AR053461-09/AR/NIAMS NIH HHS/ -- T32HL007954/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):aaf0659. doi: 10.1126/science.aaf0659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA. ; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. bpros@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102488" target="_blank"〉PubMed〈/a〉

Description: Recent studies have implicated long noncoding RNAs (lncRNAs) as regulators of many important biological processes. Here we report on the identification and characterization of a lncRNA, lnc13, that harbors a celiac disease-associated haplotype block and represses expression of certain inflammatory genes under homeostatic conditions. Lnc13 regulates gene expression by binding to hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). Upon stimulation, lnc13 levels are reduced, thereby allowing increased expression of the repressed genes. Lnc13 levels are significantly decreased in small intestinal biopsy samples from patients with celiac disease, which suggests that down-regulation of lnc13 may contribute to the inflammation seen in this disease. Furthermore, the lnc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how these single-nucleotide polymorphisms contribute to celiac disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castellanos-Rubio, Ainara -- Fernandez-Jimenez, Nora -- Kratchmarov, Radomir -- Luo, Xiaobing -- Bhagat, Govind -- Green, Peter H R -- Schneider, Robert -- Kiledjian, Megerditch -- Bilbao, Jose Ramon -- Ghosh, Sankar -- R01-AI093985/AI/NIAID NIH HHS/ -- R01-DK102180/DK/NIDDK NIH HHS/ -- R01-GM067005/GM/NIGMS NIH HHS/ -- R37-AI33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):91-5. doi: 10.1126/science.aad0467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country (UPV-EHU), BioCruces Research Institute, Leioa 48940, Basque Country, Spain. ; Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. ; Center for Celiac Disease, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Alexandria Center for Life Sciences, New York University School of Medicine, New York, NY 10016, USA. ; Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. ; Department of Microbiology and Immunology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA. sg2715@columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034373" target="_blank"〉PubMed〈/a〉

Description: Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" 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/PMC4426903/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reilly, Steven K -- Yin, Jun -- Ayoub, Albert E -- Emera, Deena -- Leng, Jing -- Cotney, Justin -- Sarro, Richard -- Rakic, Pasko -- Noonan, James P -- 099175/Z/12/Z/Wellcome Trust/United Kingdom -- DA023999/DA/NIDA NIH HHS/ -- F32 GM106628/GM/NIGMS NIH HHS/ -- GM094780/GM/NIGMS NIH HHS/ -- NS014841/NS/NINDS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 GM094780/GM/NIGMS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1155-9. doi: 10.1126/science.1260943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. ; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. james.noonan@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745175" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krupic, Julija -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):47. doi: 10.1126/science.aad3002.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. j.krupic@ucl.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26430112" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):263-4. doi: 10.1126/science.350.6258.263.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472886" target="_blank"〉PubMed〈/a〉

Description: After central nervous system (CNS) injury, inhibitory factors in the lesion scar and poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier-permeable microtubule-stabilizing drug, epothilone B (epoB), decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug-elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445125/" 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/PMC4445125/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruschel, Jorg -- Hellal, Farida -- Flynn, Kevin C -- Dupraz, Sebastian -- Elliott, David A -- Tedeschi, Andrea -- Bates, Margaret -- Sliwinski, Christopher -- Brook, Gary -- Dobrindt, Kristina -- Peitz, Michael -- Brustle, Oliver -- Norenberg, Michael D -- Blesch, Armin -- Weidner, Norbert -- Bunge, Mary Bartlett -- Bixby, John L -- Bradke, Frank -- R01 HD057632/HD/NICHD NIH HHS/ -- R01 NS059866/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):347-52. doi: 10.1126/science.aaa2958. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. ; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA. ; Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany. ; Institute for Neuropathology, RWTH Aachen University, Steinbergweg 20, 52074, Aachen, Germany. Julich-Aachen Research Alliance-Translational Brain Medicine. ; Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. ; Departments of Pathology, Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA. ; Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. frank.bradke@dzne.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25765066" target="_blank"〉PubMed〈/a〉

Description: During intracellular membrane trafficking, N-ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment protein (alpha-SNAP) disassemble the soluble NSF attachment protein receptor (SNARE) complex for recycling of the SNARE proteins. The molecular mechanism by which NSF disassembles the SNARE complex is largely unknown. Using single-molecule fluorescence spectroscopy and magnetic tweezers, we found that NSF disassembled a single SNARE complex in only one round of adenosine triphosphate (ATP) turnover. Upon ATP cleavage, the NSF hexamer developed internal tension with dissociation of phosphate ions. After latent time measuring tens of seconds, NSF released the built-up tension in a burst within 20 milliseconds, resulting in disassembly followed by immediate release of the SNARE proteins. Thus, NSF appears to use a "spring-loaded" mechanism to couple ATP hydrolysis and unfolding of substrate proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441202/" 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/PMC4441202/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryu, Je-Kyung -- Min, Duyoung -- Rah, Sang-Hyun -- Kim, Soo Jin -- Park, Yongsoo -- Kim, Haesoo -- Hyeon, Changbong -- Kim, Ho Min -- Jahn, Reinhard -- Yoon, Tae-Young -- 3P01GM072694-05S1/GM/NIGMS NIH HHS/ -- P01 GM072694/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1485-9. doi: 10.1126/science.aaa5267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Creative Research Initiative Center for Single-Molecule Systems Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea. Department of Physics, KAIST, Daejeon 305-701, South Korea. ; Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, South Korea. ; Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Korea Institute for Advanced Study, Seoul 130-722, South Korea. ; Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. rjahn@gwdg.de tyyoon@kaist.ac.kr. ; National Creative Research Initiative Center for Single-Molecule Systems Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea. Department of Physics, KAIST, Daejeon 305-701, South Korea. rjahn@gwdg.de tyyoon@kaist.ac.kr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814585" target="_blank"〉PubMed〈/a〉

Description: The actin cross-linking domain (ACD) is an actin-specific toxin produced by several pathogens, including life-threatening spp. of Vibrio cholerae, Vibrio vulnificus, and Aeromonas hydrophila. Actin cross-linking by ACD is thought to lead to slow cytoskeleton failure owing to a gradual sequestration of actin in the form of nonfunctional oligomers. Here, we found that ACD converted cytoplasmic actin into highly toxic oligomers that potently "poisoned" the ability of major actin assembly proteins, formins, to sustain actin polymerization. Thus, ACD can target the most abundant cellular protein by using actin oligomers as secondary toxins to efficiently subvert cellular functions of actin while functioning at very low doses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648357/" 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/PMC4648357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heisler, David B -- Kudryashova, Elena -- Grinevich, Dmitry O -- Suarez, Cristian -- Winkelman, Jonathan D -- Birukov, Konstantin G -- Kotha, Sainath R -- Parinandi, Narasimham L -- Vavylonis, Dimitrios -- Kovar, David R -- Kudryashov, Dmitri S -- R01 GM079265/GM/NIGMS NIH HHS/ -- R01 GM098430/GM/NIGMS NIH HHS/ -- R01 GM114666/GM/NIGMS NIH HHS/ -- R01 HL076259/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):535-9. doi: 10.1126/science.aab4090.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. ; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. ; Section of Pulmonary and Critical Care and Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. ; Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH 43210, USA. ; Department of Physics, Lehigh University, Bethlehem, PA 18015, USA. ; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. ; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA. The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. kudryashov.1@osu.edu kudryashova.1@osu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228148" target="_blank"〉PubMed〈/a〉

Description: Larger brains tend to have more folded cortices, but what makes the cortex fold has remained unknown. We show that the degree of cortical folding scales uniformly across lissencephalic and gyrencephalic species, across individuals, and within individual cortices as a function of the product of cortical surface area and the square root of cortical thickness. This relation is derived from the minimization of the effective free energy associated with cortical shape according to a simple physical model, based on known mechanisms of axonal elongation. This model also explains the scaling of the folding index of crumpled paper balls. We discuss the implications of this finding for the evolutionary and developmental origin of folding, including the newfound continuum between lissencephaly and gyrencephaly, and for pathologies such as human lissencephaly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mota, Bruno -- Herculano-Houzel, Suzana -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):74-7. doi: 10.1126/science.aaa9101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. ; Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Instituto Nacional de Neurociencia Translacional, INCT/MCT, Sao Paulo, Brazil. suzanahh@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138976" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buzsaki, Gyorgy -- New York, N.Y. -- Science. 2015 Feb 6;347(6222):612-3. doi: 10.1126/science.aaa6505.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New York University Neuroscience Institute, New York University Langone Center, New York, NY 10016, USA. gyorgy.buzsaki@nyumc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25657232" target="_blank"〉PubMed〈/a〉

Description: The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 x 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoenen, T -- Safronetz, D -- Groseth, A -- Wollenberg, K R -- Koita, O A -- Diarra, B -- Fall, I S -- Haidara, F C -- Diallo, F -- Sanogo, M -- Sarro, Y S -- Kone, A -- Togo, A C G -- Traore, A -- Kodio, M -- Dosseh, A -- Rosenke, K -- de Wit, E -- Feldmann, F -- Ebihara, H -- Munster, V J -- Zoon, K C -- Feldmann, H -- Sow, S -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):117-9. doi: 10.1126/science.aaa5646. Epub 2015 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. ; Bioinformatics and Computational Biosciences Branch, NIAID, NIH, Bethesda, MD 20892, USA. ; Center of Research and Training for HIV and Tuberculosis, University of Science, Technique and Technologies of Bamako, Mali. ; World Health Organization Office, Bamako, Mali. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. ; World Health Organization Inter-Country Support Team, Ouagadougou, Burkina Faso. ; Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA. ; Office of the Scientific Director, NIAID, NIH, Bethesda, MD 20895, USA. ; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu. ; Centre des Operations d'Urgence, Centre pour le Developpement des Vaccins (CVD-Mali), Centre National d'Appui a la lutte contre la Maladie, Ministere de la Sante et de l'Hygiene Publique, Bamako, Mali. feldmannh@niaid.nih.gov ssow@medicine.umaryland.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814067" target="_blank"〉PubMed〈/a〉

Description: Polycomb and Trithorax group proteins encode the epigenetic memory of cellular positional identity by establishing inheritable domains of repressive and active chromatin within the Hox clusters. Here we demonstrate that the CCCTC-binding factor (CTCF) functions to insulate these adjacent yet antagonistic chromatin domains during embryonic stem cell differentiation into cervical motor neurons. Deletion of CTCF binding sites within the Hox clusters results in the expansion of active chromatin into the repressive domain. CTCF functions as an insulator by organizing Hox clusters into spatially disjoint domains. Ablation of CTCF binding disrupts topological boundaries such that caudal Hox genes leave the repressed domain and become subject to transcriptional activation. Hence, CTCF is required to insulate facultative heterochromatin from impinging euchromatin to produce discrete positional identities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428148/" 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/PMC4428148/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narendra, Varun -- Rocha, Pedro P -- An, Disi -- Raviram, Ramya -- Skok, Jane A -- Mazzoni, Esteban O -- Reinberg, Danny -- GM-64844/GM/NIGMS NIH HHS/ -- GM086852/GM/NIGMS NIH HHS/ -- GM112192/GM/NIGMS NIH HHS/ -- P30 CA016087/CA/NCI NIH HHS/ -- R01 GM086852/GM/NIGMS NIH HHS/ -- R01 GM112192/GM/NIGMS NIH HHS/ -- R01 HD079682/HD/NICHD NIH HHS/ -- R01HD079682/HD/NICHD NIH HHS/ -- R37-37120/PHS HHS/ -- T32 GM007238/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1017-21. doi: 10.1126/science.1262088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. ; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. ; Department of Biology, New York University, New York, NY 10003, USA. ; Department of Biology, New York University, New York, NY 10003, USA. danny.reinberg@nyumc.org eom204@nyu.edu. ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. danny.reinberg@nyumc.org eom204@nyu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722416" target="_blank"〉PubMed〈/a〉

Description: DNA strand exchange plays a central role in genetic recombination across all kingdoms of life, but the physical basis for these reactions remains poorly defined. Using single-molecule imaging, we found that bacterial RecA and eukaryotic Rad51 and Dmc1 all stabilize strand exchange intermediates in precise three-nucleotide steps. Each step coincides with an energetic signature (0.3 kBT) that is conserved from bacteria to humans. Triplet recognition is strictly dependent on correct Watson-Crick pairing. Rad51, RecA, and Dmc1 can all step over mismatches, but only Dmc1 can stabilize mismatched triplets. This finding provides insight into why eukaryotes have evolved a meiosis-specific recombinase. We propose that canonical Watson-Crick base triplets serve as the fundamental unit of pairing interactions during DNA recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580133/" 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/PMC4580133/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Ja Yil -- Terakawa, Tsuyoshi -- Qi, Zhi -- Steinfeld, Justin B -- Redding, Sy -- Kwon, YoungHo -- Gaines, William A -- Zhao, Weixing -- Sung, Patrick -- Greene, Eric C -- CA146940/CA/NCI NIH HHS/ -- GM074739/GM/NIGMS NIH HHS/ -- R01 CA146940/CA/NCI NIH HHS/ -- R01 ES015252/ES/NIEHS NIH HHS/ -- R01 GM074739/GM/NIGMS NIH HHS/ -- R01ES015252/ES/NIEHS NIH HHS/ -- T32 GM007367/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):977-81. doi: 10.1126/science.aab2666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan. ; Department of Chemistry, Columbia University, New York, NY, USA. ; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, USA. ; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA. Howard Hughes Medical Institute, Columbia University, New York, NY, USA. ecg2108@cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315438" target="_blank"〉PubMed〈/a〉

Description: Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380271/" 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/PMC4380271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neafsey, Daniel E -- Waterhouse, Robert M -- Abai, Mohammad R -- Aganezov, Sergey S -- Alekseyev, Max A -- Allen, James E -- Amon, James -- Arca, Bruno -- Arensburger, Peter -- Artemov, Gleb -- Assour, Lauren A -- Basseri, Hamidreza -- Berlin, Aaron -- Birren, Bruce W -- Blandin, Stephanie A -- Brockman, Andrew I -- Burkot, Thomas R -- Burt, Austin -- Chan, Clara S -- Chauve, Cedric -- Chiu, Joanna C -- Christensen, Mikkel -- Costantini, Carlo -- Davidson, Victoria L M -- Deligianni, Elena -- Dottorini, Tania -- Dritsou, Vicky -- Gabriel, Stacey B -- Guelbeogo, Wamdaogo M -- Hall, Andrew B -- Han, Mira V -- Hlaing, Thaung -- Hughes, Daniel S T -- Jenkins, Adam M -- Jiang, Xiaofang -- Jungreis, Irwin -- Kakani, Evdoxia G -- Kamali, Maryam -- Kemppainen, Petri -- Kennedy, Ryan C -- Kirmitzoglou, Ioannis K -- Koekemoer, Lizette L -- Laban, Njoroge -- Langridge, Nicholas -- Lawniczak, Mara K N -- Lirakis, Manolis -- Lobo, Neil F -- Lowy, Ernesto -- MacCallum, Robert M -- Mao, Chunhong -- Maslen, Gareth -- Mbogo, Charles -- McCarthy, Jenny -- Michel, Kristin -- Mitchell, Sara N -- Moore, Wendy -- Murphy, Katherine A -- Naumenko, Anastasia N -- Nolan, Tony -- Novoa, Eva M -- O'Loughlin, Samantha -- Oringanje, Chioma -- Oshaghi, Mohammad A -- Pakpour, Nazzy -- Papathanos, Philippos A -- Peery, Ashley N -- Povelones, Michael -- Prakash, Anil -- Price, David P -- Rajaraman, Ashok -- Reimer, Lisa J -- Rinker, David C -- Rokas, Antonis -- Russell, Tanya L -- Sagnon, N'Fale -- Sharakhova, Maria V -- Shea, Terrance -- Simao, Felipe A -- Simard, Frederic -- Slotman, Michel A -- Somboon, Pradya -- Stegniy, Vladimir -- Struchiner, Claudio J -- Thomas, Gregg W C -- Tojo, Marta -- Topalis, Pantelis -- Tubio, Jose M C -- Unger, Maria F -- Vontas, John -- Walton, Catherine -- Wilding, Craig S -- Willis, Judith H -- Wu, Yi-Chieh -- Yan, Guiyun -- Zdobnov, Evgeny M -- Zhou, Xiaofan -- Catteruccia, Flaminia -- Christophides, George K -- Collins, Frank H -- Cornman, Robert S -- Crisanti, Andrea -- Donnelly, Martin J -- Emrich, Scott J -- Fontaine, Michael C -- Gelbart, William -- Hahn, Matthew W -- Hansen, Immo A -- Howell, Paul I -- Kafatos, Fotis C -- Kellis, Manolis -- Lawson, Daniel -- Louis, Christos -- Luckhart, Shirley -- Muskavitch, Marc A T -- Ribeiro, Jose M -- Riehle, Michael A -- Sharakhov, Igor V -- Tu, Zhijian -- Zwiebel, Laurence J -- Besansky, Nora J -- 092654/Wellcome Trust/United Kingdom -- R01 AI050243/AI/NIAID NIH HHS/ -- R01 AI063508/AI/NIAID NIH HHS/ -- R01 AI073745/AI/NIAID NIH HHS/ -- R01 AI076584/AI/NIAID NIH HHS/ -- R01 AI080799/AI/NIAID NIH HHS/ -- R01 AI104956/AI/NIAID NIH HHS/ -- R21 AI101459/AI/NIAID NIH HHS/ -- R56 AI107263/AI/NIAID NIH HHS/ -- SC1 AI109055/AI/NIAID NIH HHS/ -- U19 AI089686/AI/NIAID NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):1258522. doi: 10.1126/science.1258522. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. neafsey@broadinstitute.org nbesansk@nd.edu. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Medical Entomology and Vector Control, School of Public Health and Institute of Health Researches, Tehran University of Medical Sciences, Tehran, Iran. ; George Washington University, Department of Mathematics and Computational Biology Institute, 45085 University Drive, Ashburn, VA 20147, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; National Vector Borne Disease Control Programme, Ministry of Health, Tafea Province, Vanuatu. ; Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. ; Department of Biological Sciences, California State Polytechnic-Pomona, 3801 West Temple Avenue, Pomona, CA 91768, USA. ; Tomsk State University, 36 Lenina Avenue, Tomsk, Russia. ; Department of Computer Science and Engineering, Eck Institute for Global Health, 211B Cushing Hall, University of Notre Dame, Notre Dame, IN 46556, USA. ; Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Inserm, U963, F-67084 Strasbourg, France. CNRS, UPR9022, IBMC, F-67084 Strasbourg, France. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. ; Faculty of Medicine, Health and Molecular Science, Australian Institute of Tropical Health Medicine, James Cook University, Cairns 4870, Australia. ; Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. ; Department of Mathematics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. ; Department of Entomology and Nematology, One Shields Avenue, University of California-Davis, Davis, CA 95616, USA. ; Institut de Recherche pour le Developpement, Unites Mixtes de Recherche Maladies Infectieuses et Vecteurs Ecologie, Genetique, Evolution et Controle, 911, Avenue Agropolis, BP 64501 Montpellier, France. ; Division of Biology, Kansas State University, 271 Chalmers Hall, Manhattan, KS 66506, USA. ; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. ; Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Genomics Platform, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou 01 BP 2208, Burkina Faso. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; School of Life Sciences, University of Nevada, Las Vegas, NV 89154, USA. ; Department of Medical Research, No. 5 Ziwaka Road, Dagon Township, Yangon 11191, Myanmar. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. ; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita degli Studi di Perugia, Perugia, Italy. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Computational Evolutionary Biology Group, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Bioinformatics Research Laboratory, Department of Biological Sciences, New Campus, University of Cyprus, CY 1678 Nicosia, Cyprus. ; Wits Research Institute for Malaria, Faculty of Health Sciences, and Vector Control Reference Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, Johannesburg, South Africa. ; National Museums of Kenya, P.O. Box 40658-00100, Nairobi, Kenya. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. ; Virginia Bioinformatics Institute, 1015 Life Science Circle, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, P.O. Box 230-80108, Kilifi, Kenya. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. ; Department of Entomology, 1140 East South Campus Drive, Forbes 410, University of Arizona, Tucson, AZ 85721, USA. ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, One Shields Avenue, Davis, CA 95616, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA. ; Regional Medical Research Centre NE, Indian Council of Medical Research, P.O. Box 105, Dibrugarh-786 001, Assam, India. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Entomology, Texas A&M University, College Station, TX 77807, USA. ; Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. ; Fundacao Oswaldo Cruz, Avenida Brasil 4365, RJ Brazil. Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. ; School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Department of Physiology, School of Medicine, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK. ; School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK. ; Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Computer Science, Harvey Mudd College, Claremont, CA 91711, USA. ; Program in Public Health, College of Health Sciences, University of California, Irvine, Hewitt Hall, Irvine, CA 92697, USA. ; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SJ, UK. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. Centre of Evolutionary and Ecological Studies (Marine Evolution and Conservation group), University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. ; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. ; Department of Biology, Indiana University, Bloomington, IN 47405, USA. School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Centers for Disease Control and Prevention, 1600 Clifton Road NE MSG49, Atlanta, GA 30329, USA. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Departments of Biological Sciences and Pharmacology, Institutes for Chemical Biology, Genetics and Global Health, Vanderbilt University and Medical Center, Nashville, TN 37235, USA. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. neafsey@broadinstitute.org nbesansk@nd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554792" target="_blank"〉PubMed〈/a〉

Description: Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities ("suboptimization"). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain "superenhancers," circumvent this trade-off in specificity and activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farley, Emma K -- Olson, Katrina M -- Zhang, Wei -- Brandt, Alexander J -- Rokhsar, Daniel S -- Levine, Michael S -- GM46638/GM/NIGMS NIH HHS/ -- NS076542/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):325-8. doi: 10.1126/science.aac6948.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. msl2@princeton.edu ekfarley@princeton.edu. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. ; Department of Medicine, University of California, San Diego, CA 92093-0688, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720-3200, USA. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472909" target="_blank"〉PubMed〈/a〉

Description: The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nie, Yonggang -- Speakman, John R -- Wu, Qi -- Zhang, Chenglin -- Hu, Yibo -- Xia, Maohua -- Yan, Li -- Hambly, Catherine -- Wang, Lu -- Wei, Wei -- Zhang, Jinguo -- Wei, Fuwen -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):171-4. doi: 10.1126/science.aab2413.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; Beijing Key Laboratory of Captive Wildlife Technologies, Beijing Zoo, Beijing, China. ; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, UK. ; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. ; Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. weifw@ioz.ac.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160943" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):261-2. doi: 10.1126/science.350.6258.261.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472885" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):677. doi: 10.1126/science.349.6249.677.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273032" target="_blank"〉PubMed〈/a〉

Description: Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Ritchie -- Romero, Gabriela -- Christiansen, Michael G -- Mohr, Alan -- Anikeeva, Polina -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1477-80. doi: 10.1126/science.1261821. Epub 2015 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. anikeeva@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25765068" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):114. doi: 10.1126/science.347.6218.114.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25573999" target="_blank"〉PubMed〈/a〉

Description: Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, a limited understanding of this RNA-binding protein (RBP) impedes the clarification of pathogenic mechanisms underlying TDP-43 proteinopathy. In contrast to RBPs that regulate splicing of conserved exons, we found that TDP-43 repressed the splicing of nonconserved cryptic exons, maintaining intron integrity. When TDP-43 was depleted from mouse embryonic stem cells, these cryptic exons were spliced into messenger RNAs, often disrupting their translation and promoting nonsense-mediated decay. Moreover, enforced repression of cryptic exons prevented cell death in TDP-43-deficient cells. Furthermore, repression of cryptic exons was impaired in ALS-FTD cases, suggesting that this splicing defect could potentially underlie TDP-43 proteinopathy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ling, Jonathan P -- Pletnikova, Olga -- Troncoso, Juan C -- Wong, Philip C -- P50AG05146/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):650-5. doi: 10.1126/science.aab0983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. wong@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250685" target="_blank"〉PubMed〈/a〉

Description: The hippocampus computes diverse information involving spatial memory, anxiety, or reward and directly projects to several brain areas. Are different computations transmitted to all downstream targets uniformly, or does the hippocampus selectively route information according to content and target region? By recording from ventral hippocampal CA1 neurons in rats during different behavioral tasks and determining axonal projections with optogenetics, we observed subsets of neurons changing firing at places of elevated anxiety or changing activity during goal approach. Anxiety-related firing was selectively increased in neurons projecting to the prefrontal cortex. Goal-directed firing was most prominent in neurons targeting the nucleus accumbens; and triple-projecting neurons, targeting the prefrontal cortex, amygdala, and nucleus accumbens, were most active during tasks and sharp wave/ripples. Thus, hippocampal neurons route distinct behavior-contingent information selectively to different target areas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciocchi, S -- Passecker, J -- Malagon-Vina, H -- Mikus, N -- Klausberger, T -- New York, N.Y. -- Science. 2015 May 1;348(6234):560-3. doi: 10.1126/science.aaa3245.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Brain Research, Department for Cognitive Neurobiology, Medical University Vienna, Spitalgasse 4, 1090 Vienna, Austria. stephane.ciocchi@meduniwien.ac.at thomas.klausberger@meduniwien.ac.at. ; Center for Brain Research, Department for Cognitive Neurobiology, Medical University Vienna, Spitalgasse 4, 1090 Vienna, Austria. ; Center for Brain Research, Department for Cognitive Neurobiology, Medical University Vienna, Spitalgasse 4, 1090 Vienna, Austria. Medical Research Council, Anatomical Neuropharmacology Unit, Oxford University, Mansfield Road, Oxford OX1 3TH, UK. stephane.ciocchi@meduniwien.ac.at thomas.klausberger@meduniwien.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931556" target="_blank"〉PubMed〈/a〉

Description: Bacterial adaptive immunity uses CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) proteins together with CRISPR transcripts for foreign DNA degradation. In type II CRISPR-Cas systems, activation of Cas9 endonuclease for DNA recognition upon guide RNA binding occurs by an unknown mechanism. Crystal structures of Cas9 bound to single-guide RNA reveal a conformation distinct from both the apo and DNA-bound states, in which the 10-nucleotide RNA "seed" sequence required for initial DNA interrogation is preordered in an A-form conformation. This segment of the guide RNA is essential for Cas9 to form a DNA recognition-competent structure that is poised to engage double-stranded DNA target sequences. We construe this as convergent evolution of a "seed" mechanism reminiscent of that used by Argonaute proteins during RNA interference in eukaryotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Fuguo -- Zhou, Kaihong -- Ma, Linlin -- Gressel, Saskia -- Doudna, Jennifer A -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 26;348(6242):1477-81. doi: 10.1126/science.aab1452.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ; Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Department of Chemistry, University of California, Berkeley, CA 94720, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Innovative Genomics Initiative, University of California, Berkeley, CA 94720, USA. doudna@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113724" target="_blank"〉PubMed〈/a〉

Description: Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720525/" 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/PMC4720525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sigova, Alla A -- Abraham, Brian J -- Ji, Xiong -- Molinie, Benoit -- Hannett, Nancy M -- Guo, Yang Eric -- Jangi, Mohini -- Giallourakis, Cosmas C -- Sharp, Phillip A -- Young, Richard A -- HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):978-81. doi: 10.1126/science.aad3346. Epub 2015 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. ; Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02140, USA. ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. young@wi.mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516199" target="_blank"〉PubMed〈/a〉

Description: Notch receptors guide mammalian cell fate decisions by engaging the proteins Jagged and Delta-like (DLL). The 2.3 angstrom resolution crystal structure of the interacting regions of the Notch1-DLL4 complex reveals a two-site, antiparallel binding orientation assisted by Notch1 O-linked glycosylation. Notch1 epidermal growth factor-like repeats 11 and 12 interact with the DLL4 Delta/Serrate/Lag-2 (DSL) domain and module at the N-terminus of Notch ligands (MNNL) domains, respectively. Threonine and serine residues on Notch1 are functionalized with O-fucose and O-glucose, which act as surrogate amino acids by making specific, and essential, contacts to residues on DLL4. The elucidation of a direct chemical role for O-glycans in Notch1 ligand engagement demonstrates how, by relying on posttranslational modifications of their ligand binding sites, Notch proteins have linked their functional capacity to developmentally regulated biosynthetic pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445638/" 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/PMC4445638/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luca, Vincent C -- Jude, Kevin M -- Pierce, Nathan W -- Nachury, Maxence V -- Fischer, Suzanne -- Garcia, K Christopher -- 1R01-GM097015/GM/NIGMS NIH HHS/ -- R01 GM097015/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):847-53. doi: 10.1126/science.1261093.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. kcgarcia@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700513" target="_blank"〉PubMed〈/a〉

Description: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winzer, Thilo -- Kern, Marcelo -- King, Andrew J -- Larson, Tony R -- Teodor, Roxana I -- Donninger, Samantha L -- Li, Yi -- Dowle, Adam A -- Cartwright, Jared -- Bates, Rachel -- Ashford, David -- Thomas, Jerry -- Walker, Carol -- Bowser, Tim A -- Graham, Ian A -- BB/K018809/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):309-12. doi: 10.1126/science.aab1852. Epub 2015 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK. ; Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK. ; GlaxoSmithKline, 1061 Mountain Highway, Post Office Box 168, Boronia, Victoria 3155, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26113639" target="_blank"〉PubMed〈/a〉

Description: Navigation depends on multiple neural systems that encode the moment-to-moment changes in an animal's direction and location in space. These include head direction (HD) cells representing the orientation of the head and grid cells that fire at multiple locations, forming a repeating hexagonal grid pattern. Computational models hypothesize that generation of the grid cell signal relies upon HD information that ascends to the hippocampal network via the anterior thalamic nuclei (ATN). We inactivated or lesioned the ATN and subsequently recorded single units in the entorhinal cortex and parasubiculum. ATN manipulation significantly disrupted grid and HD cell characteristics while sparing theta rhythmicity in these regions. These results indicate that the HD signal via the ATN is necessary for the generation and function of grid cell activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476794/" 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/PMC4476794/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winter, Shawn S -- Clark, Benjamin J -- Taube, Jeffrey S -- NS053907/NS/NINDS NIH HHS/ -- R01 MH048924/MH/NIMH NIH HHS/ -- R01 NS053907/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 20;347(6224):870-4. doi: 10.1126/science.1259591. Epub 2015 Feb 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychological and Brain Sciences, Center for Cognitive Neuroscience, Dartmouth College, Hanover, NH 03755, USA. ; Department of Psychological and Brain Sciences, Center for Cognitive Neuroscience, Dartmouth College, Hanover, NH 03755, USA. jeffrey.taube@dartmouth.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700518" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2015 May 22;348(6237):849. doi: 10.1126/science.348.6237.849.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999487" target="_blank"〉PubMed〈/a〉

Description: Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681433/" 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/PMC4681433/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arner, Erik -- Daub, Carsten O -- Vitting-Seerup, Kristoffer -- Andersson, Robin -- Lilje, Berit -- Drablos, Finn -- Lennartsson, Andreas -- Ronnerblad, Michelle -- Hrydziuszko, Olga -- Vitezic, Morana -- Freeman, Tom C -- Alhendi, Ahmad M N -- Arner, Peter -- Axton, Richard -- Baillie, J Kenneth -- Beckhouse, Anthony -- Bodega, Beatrice -- Briggs, James -- Brombacher, Frank -- Davis, Margaret -- Detmar, Michael -- Ehrlund, Anna -- Endoh, Mitsuhiro -- Eslami, Afsaneh -- Fagiolini, Michela -- Fairbairn, Lynsey -- Faulkner, Geoffrey J -- Ferrai, Carmelo -- Fisher, Malcolm E -- Forrester, Lesley -- Goldowitz, Daniel -- Guler, Reto -- Ha, Thomas -- Hara, Mitsuko -- Herlyn, Meenhard -- Ikawa, Tomokatsu -- Kai, Chieko -- Kawamoto, Hiroshi -- Khachigian, Levon M -- Klinken, S Peter -- Kojima, Soichi -- Koseki, Haruhiko -- Klein, Sarah -- Mejhert, Niklas -- Miyaguchi, Ken -- Mizuno, Yosuke -- Morimoto, Mitsuru -- Morris, Kelly J -- Mummery, Christine -- Nakachi, Yutaka -- Ogishima, Soichi -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry -- Passier, Robert -- Patrikakis, Margaret -- Pombo, Ana -- Qin, Xian-Yang -- Roy, Sugata -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schwegmann, Anita -- Sugiyama, Daisuke -- Swoboda, Rolf -- Tanaka, Hiroshi -- Tomoiu, Andru -- Winteringham, Louise N -- Wolvetang, Ernst -- Yanagi-Mizuochi, Chiyo -- Yoneda, Misako -- Zabierowski, Susan -- Zhang, Peter -- Abugessaisa, Imad -- Bertin, Nicolas -- Diehl, Alexander D -- Fukuda, Shiro -- Furuno, Masaaki -- Harshbarger, Jayson -- Hasegawa, Akira -- Hori, Fumi -- Ishikawa-Kato, Sachi -- Ishizu, Yuri -- Itoh, Masayoshi -- Kawashima, Tsugumi -- Kojima, Miki -- Kondo, Naoto -- Lizio, Marina -- Meehan, Terrence F -- Mungall, Christopher J -- Murata, Mitsuyoshi -- Nishiyori-Sueki, Hiromi -- Sahin, Serkan -- Nagao-Sato, Sayaka -- Severin, Jessica -- de Hoon, Michiel J L -- Kawai, Jun -- Kasukawa, Takeya -- Lassmann, Timo -- Suzuki, Harukazu -- Kawaji, Hideya -- Summers, Kim M -- Wells, Christine -- FANTOM Consortium -- Hume, David A -- Forrest, Alistair R R -- Sandelin, Albin -- Carninci, Piero -- Hayashizaki, Yoshihide -- P30 CA010815/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):1010-4. doi: 10.1126/science.1259418. Epub 2015 Feb 12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678556" target="_blank"〉PubMed〈/a〉

Description: The 26S proteasome is a key player in eukaryotic protein quality control and in the regulation of numerous cellular processes. Here, we describe quantitative in situ structural studies of this highly dynamic molecular machine in intact hippocampal neurons. We used electron cryotomography with the Volta phase plate, which allowed high fidelity and nanometer precision localization of 26S proteasomes. We undertook a molecular census of single- and double-capped proteasomes and assessed the conformational states of individual complexes. Under the conditions of the experiment-that is, in the absence of proteotoxic stress-only 20% of the 26S proteasomes were engaged in substrate processing. The remainder was in the substrate-accepting ground state. These findings suggest that in the absence of stress, the capacity of the proteasome system is not fully used.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asano, Shoh -- Fukuda, Yoshiyuki -- Beck, Florian -- Aufderheide, Antje -- Forster, Friedrich -- Danev, Radostin -- Baumeister, Wolfgang -- New York, N.Y. -- Science. 2015 Jan 23;347(6220):439-42. doi: 10.1126/science.1261197.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. ; Department of Molecular Structural Biology, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. baumeist@biochem.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25613890" target="_blank"〉PubMed〈/a〉

Description: Nonalcoholic fatty liver disease (NAFLD) is a major factor in the pathogenesis of type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH). The mitochondrial protonophore 2,4 dinitrophenol (DNP) has beneficial effects on NAFLD, insulin resistance, and obesity in preclinical models but is too toxic for clinical use. We developed a controlled-release oral formulation of DNP, called CRMP (controlled-release mitochondrial protonophore), that produces mild hepatic mitochondrial uncoupling. In rat models, CRMP reduced hypertriglyceridemia, insulin resistance, hepatic steatosis, and diabetes. It also normalized plasma transaminase concentrations, ameliorated liver fibrosis, and improved hepatic protein synthetic function in a methionine/choline-deficient rat model of NASH. Chronic treatment with CRMP was not associated with any systemic toxicity. These data offer proof of concept that mild hepatic mitochondrial uncoupling may be a safe and effective therapy for the related epidemics of metabolic syndrome, T2D, and NASH.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495920/" 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/PMC4495920/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, Rachel J -- Zhang, Dongyan -- Zhang, Xian-Man -- Boyer, James L -- Shulman, Gerald I -- P30 DK-34989/DK/NIDDK NIH HHS/ -- P30 DK-45735/DK/NIDDK NIH HHS/ -- P30 DK034989/DK/NIDDK NIH HHS/ -- P30 DK045735/DK/NIDDK NIH HHS/ -- R01 DK-40936/DK/NIDDK NIH HHS/ -- R01 DK040936/DK/NIDDK NIH HHS/ -- R24 DK-085638/DK/NIDDK NIH HHS/ -- T32 DK-101019/DK/NIDDK NIH HHS/ -- U24 DK-059635/DK/NIDDK NIH HHS/ -- UL1 TR-000142/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1253-6. doi: 10.1126/science.aaa0672. Epub 2015 Feb 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA. Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA. ; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA. ; Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. ; Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA. ; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA. Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA. gerald.shulman@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25721504" target="_blank"〉PubMed〈/a〉

Description: Neuronal circuits produce self-sustaining sequences of activity patterns, but the precise mechanisms remain unknown. Here we provide evidence for autoassociative dynamics in sequence generation. During sharp-wave ripple (SWR) events, hippocampal neurons express sequenced reactivations, which we show are composed of discrete attractors. Each attractor corresponds to a single location, the representation of which sharpens over the course of several milliseconds, as the reactivation focuses at that location. Subsequently, the reactivation transitions rapidly to a spatially discontiguous location. This alternation between sharpening and transition occurs repeatedly within individual SWRs and is locked to the slow-gamma (25 to 50 hertz) rhythm. These findings support theoretical notions of neural network function and reveal a fundamental discretization in the retrieval of memory in the hippocampus, together with a function for gamma oscillations in the control of attractor dynamics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pfeiffer, Brad E -- Foster, David J -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):180-3. doi: 10.1126/science.aaa9633.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. david.foster@jhu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160946" target="_blank"〉PubMed〈/a〉

Description: The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Psi(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492308/" 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/PMC4492308/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keane, Sarah C -- Heng, Xiao -- Lu, Kun -- Kharytonchyk, Siarhei -- Ramakrishnan, Venkateswaran -- Carter, Gregory -- Barton, Shawn -- Hosic, Azra -- Florwick, Alyssa -- Santos, Justin -- Bolden, Nicholas C -- McCowin, Sayo -- Case, David A -- Johnson, Bruce A -- Salemi, Marco -- Telesnitsky, Alice -- Summers, Michael F -- 2T34 GM008663/GM/NIGMS NIH HHS/ -- P50 GM 103297/GM/NIGMS NIH HHS/ -- P50 GM103297/GM/NIGMS NIH HHS/ -- R01 GM042561/GM/NIGMS NIH HHS/ -- R01 GM42561/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 22;348(6237):917-21. doi: 10.1126/science.aaa9266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. ; Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA. ; One Moon Scientific, Incorporated, 839 Grant Avenue, Westfield, NJ 07090, USA, and City University of New York (CUNY) Advanced Science Research Center, 85 St. Nicholas Terrace, New York, NY 10031, USA. ; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, and Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-5620, USA. summers@hhmi.umbc.edu ateles@umich.edu. ; Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA. summers@hhmi.umbc.edu ateles@umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999508" target="_blank"〉PubMed〈/a〉

Description: The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a 〉1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Luhan -- Guell, Marc -- Niu, Dong -- George, Haydy -- Lesha, Emal -- Grishin, Dennis -- Aach, John -- Shrock, Ellen -- Xu, Weihong -- Poci, Jurgen -- Cortazio, Rebeca -- Wilkinson, Robert A -- Fishman, Jay A -- Church, George -- P50 HG005550/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1101-4. doi: 10.1126/science.aad1191. Epub 2015 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. gchurch@genetics.med.harvard.edu luhan.yang@egenesisbio.com. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA. eGenesis Biosciences, Boston, MA 02115, USA. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ; Transplant Infectious Disease and Compromised Host Program, Massachusetts General Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26456528" target="_blank"〉PubMed〈/a〉

Description: Most spontaneous DNA double-strand breaks (DSBs) result from replication-fork breakage. Break-induced replication (BIR), a genome rearrangement-prone repair mechanism that requires the Pol32/POLD3 subunit of eukaryotic DNA Poldelta, was proposed to repair broken forks, but how genome destabilization is avoided was unknown. We show that broken fork repair initially uses error-prone Pol32-dependent synthesis, but that mutagenic synthesis is limited to within a few kilobases from the break by Mus81 endonuclease and a converging fork. Mus81 suppresses template switches between both homologous sequences and diverged human Alu repetitive elements, highlighting its importance for stability of highly repetitive genomes. We propose that lack of a timely converging fork or Mus81 may propel genome instability observed in cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mayle, Ryan -- Campbell, Ian M -- Beck, Christine R -- Yu, Yang -- Wilson, Marenda -- Shaw, Chad A -- Bjergbaek, Lotte -- Lupski, James R -- Ira, Grzegorz -- F31 NS083159/NS/NINDS NIH HHS/ -- GM080600/GM/NIGMS NIH HHS/ -- HG006542/HG/NHGRI NIH HHS/ -- NS058529/NS/NINDS NIH HHS/ -- NS083159/NS/NINDS NIH HHS/ -- R01 GM080600/GM/NIGMS NIH HHS/ -- R01 NS058529/NS/NINDS NIH HHS/ -- U54 HG006542/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):742-7. doi: 10.1126/science.aaa8391.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. ; Department of Molecular Biology and Genetics, University of Aarhus, Aarhus 8000, Denmark. ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Department of Pediatrics, and Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Texas Children's Hospital, Houston, TX 77030, USA. ; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. gira@bcm.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26273056" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pulla, Priyanka -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):15-6. doi: 10.1126/science.348.6230.15.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25838358" target="_blank"〉PubMed〈/a〉

Description: The Protoaurignacian culture is pivotal to the debate about the timing of the arrival of modern humans in western Europe and the demise of Neandertals. However, which group is responsible for this culture remains uncertain. We investigated dental remains associated with the Protoaurignacian. The lower deciduous incisor from Riparo Bombrini is modern human, based on its morphology. The upper deciduous incisor from Grotta di Fumane contains ancient mitochondrial DNA of a modern human type. These teeth are the oldest human remains in an Aurignacian-related archaeological context, confirming that by 41,000 calendar years before the present, modern humans bearing Protoaurignacian culture spread into southern Europe. Because the last Neandertals date to 41,030 to 39,260 calendar years before the present, we suggest that the Protoaurignacian triggered the demise of Neandertals in this area.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benazzi, S -- Slon, V -- Talamo, S -- Negrino, F -- Peresani, M -- Bailey, S E -- Sawyer, S -- Panetta, D -- Vicino, G -- Starnini, E -- Mannino, M A -- Salvadori, P A -- Meyer, M -- Paabo, S -- Hublin, J-J -- New York, N.Y. -- Science. 2015 May 15;348(6236):793-6. doi: 10.1126/science.aaa2773. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. stefano.benazzi@unibo.it. ; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Dipartimento di Antichita, Filosofia, Storia e Geografia, Universita di Genova, Via Balbi 2, 16126 Genova, Italy. ; Sezione di Scienze Preistoriche e Antropologiche, Dipartimento di Studi Umanistici, Corso Ercole I d'Este 32, Universita di Ferrara, 44100 Ferrara, Italy. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. Center for the Study of Human Origins, Department of Anthropology, New York University, 25 Waverly Place, New York, NY 10003, USA. ; CNR Institute of Clinical Physiology, National Research Council, Via G. Moruzzi 1, 56124 Pisa, Italy. ; Museo Archeologico del Finale, Chiostri di Santa Caterina, 17024 Finale Ligure Borgo, Italy. ; Scuola di Scienze Umanistiche, Dipartimento di Studi Storici, Universita di Torino, via S. Ottavio 20, 10124 Torino, Italy. Museo Preistorico Nazionale dei Balzi Rossi, Via Balzi Rossi 9, 18039 Ventimiglia, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908660" target="_blank"〉PubMed〈/a〉