ALBERT

Description: The human cytomegalovirus (HCMV) genome was sequenced 20 years ago. However, like those of other complex viruses, our understanding of its protein coding potential is far from complete. We used ribosome profiling and transcript analysis to experimentally define the HCMV translation products and follow their temporal expression. We identified hundreds of previously unidentified open reading frames and confirmed a fraction by means of mass spectrometry. We found that regulated use of alternative transcript start sites plays a broad role in enabling tight temporal control of HCMV protein expression and allowing multiple distinct polypeptides to be generated from a single genomic locus. Our results reveal an unanticipated complexity to the HCMV coding capacity and illustrate the role of regulated changes in transcript start sites in generating this complexity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817102/" 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/PMC3817102/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stern-Ginossar, Noam -- Weisburd, Ben -- Michalski, Annette -- Le, Vu Thuy Khanh -- Hein, Marco Y -- Huang, Sheng-Xiong -- Ma, Ming -- Shen, Ben -- Qian, Shu-Bing -- Hengel, Hartmut -- Mann, Matthias -- Ingolia, Nicholas T -- Weissman, Jonathan S -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Nov 23;338(6110):1088-93. doi: 10.1126/science.1227919.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisico, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23180859" target="_blank"〉PubMed〈/a〉

Description: Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication. These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431581/" 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/PMC4431581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciancanelli, Michael J -- Huang, Sarah X L -- Luthra, Priya -- Garner, Hannah -- Itan, Yuval -- Volpi, Stefano -- Lafaille, Fabien G -- Trouillet, Celine -- Schmolke, Mirco -- Albrecht, Randy A -- Israelsson, Elisabeth -- Lim, Hye Kyung -- Casadio, Melina -- Hermesh, Tamar -- Lorenzo, Lazaro -- Leung, Lawrence W -- Pedergnana, Vincent -- Boisson, Bertrand -- Okada, Satoshi -- Picard, Capucine -- Ringuier, Benedicte -- Troussier, Francoise -- Chaussabel, Damien -- Abel, Laurent -- Pellier, Isabelle -- Notarangelo, Luigi D -- Garcia-Sastre, Adolfo -- Basler, Christopher F -- Geissmann, Frederic -- Zhang, Shen-Ying -- Snoeck, Hans-Willem -- Casanova, Jean-Laurent -- 1U19AI109945/AI/NIAID NIH HHS/ -- 5R01AI100887/AI/NIAID NIH HHS/ -- 5R01NS072381/NS/NINDS NIH HHS/ -- 8UL1TR000043/TR/NCATS NIH HHS/ -- HHSN272201400008C/PHS HHS/ -- R01 AI100887/AI/NIAID NIH HHS/ -- R01 NS072381/NS/NINDS NIH HHS/ -- U19 AI109945/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):448-53. doi: 10.1126/science.aaa1578. Epub 2015 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. ; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA. Department of Medicine, Columbia University Medical Center, New York, NY, USA. ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK. ; Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy. ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. Study Centre for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France. ; Pediatric Intensive Care Unit, University Hospital, Angers, France. ; General Pediatrics Unit, University Hospital, Angers, France. ; Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. Department of Systems Biology, Sidra Medical and Research Center, Doha, Qatar. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. ; Pediatric Immunology, Hematology and Oncology Unit, University Hospital Centre of Angers, Angers, France. INSERM U892, CNRS U6299, Angers, France. ; Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA. ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. Pediatric Immuno-Hematology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France. Howard Hughes Medical Institute, New York, NY, USA. jean-laurent.casanova@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814066" target="_blank"〉PubMed〈/a〉

Description: The tuberal nucleus (TN) is a surprisingly understudied brain region. We found that somatostatin (SST) neurons in the TN, which is known to exhibit pathological or cytological changes in human neurodegenerative diseases, play a crucial role in regulating feeding in mice. GABAergic tuberal SST ( TN SST) neurons were activated by hunger and by the hunger hormone, ghrelin. Activation of TN SST neurons promoted feeding, whereas inhibition reduced it via projections to the paraventricular nucleus and bed nucleus of the stria terminalis. Ablation of TN SST neurons reduced body weight gain and food intake. These findings reveal a previously unknown mechanism of feeding regulation that operates through orexigenic TN SST neurons, providing a new perspective for understanding appetite changes.

Description: 〈p〉Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. Here, our genome-wide transcriptome analysis of HERVs revealed that a primate long noncoding RNA, which we dubbed TROJAN, was highly expressed in human triple-negative breast cancer (TNBC). TROJAN promoted TNBC proliferation and invasion and indicated poor patient outcomes. We further confirmed that TROJAN could bind to ZMYND8, a metastasis-repressing factor, and increase its degradation through the ubiquitin-proteasome pathway by repelling ZNF592. TROJAN also epigenetically up-regulated metastasis-related genes in multiple cell lines. Correlations between TROJAN and ZMYND8 were subsequently confirmed in clinical samples. Furthermore, our study verified that antisense oligonucleotide therapy targeting TROJAN substantially suppressed TNBC progression in vivo. In conclusion, the long noncoding RNA TROJAN promotes TNBC progression and serves as a potential therapeutic target.〈/p〉

Description: 〈p〉High-dimensional Bell-like states are necessary for increasing the channel capacity of the quantum protocol. However, their preparation and measurement are still huge challenges, especially for the latter. Here, we prepare an initial eight-dimensional Bell-like state based on hyperentanglement of spin and orbital angular momentum (OAM) of the first and the third orders. We design simple unitary operations to produce eight Bell-like states, which can be distinguished completely in theory among each other. We propose and illustrate a multiple projective measurement scheme composed of only linear optical elements and experimentally demonstrate that all the eight hyperentangled Bell-like states can be completely distinguished by our scheme. Our idea of manipulating the eight Bell-like states is beneficial to achieve the 3-bit channel capacity of quantum protocol, opening the door for extending applications of OAM states in future quantum information technology.〈/p〉

Description: End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. To reduce the morbidity and mortality associated with lung disease, new therapeutic strategies aimed at promoting lung repair and increasing the number of donor lungs available for transplantation are being explored. Because of the extreme complexity of this organ, previous attempts at bioengineering functional lungs from fully decellularized or synthetic scaffolds lacking functional vasculature have been largely unsuccessful. An intact vascular network is critical not only for maintaining the blood-gas barrier and allowing for proper graft function but also for supporting the regenerative cells. We therefore developed an airway-specific approach to removing the pulmonary epithelium, while maintaining the viability and function of the vascular endothelium, using a rat model. The resulting vascularized lung grafts supported the attachment and growth of human adult pulmonary cells and stem cell–derived lung-specified epithelial cells. We propose that de-epithelialization of the lung with preservation of intact vasculature could facilitate cell therapy of pulmonary epithelium and enable bioengineering of functional lungs for transplantation.

Description: 〈p〉Topological matter is known to exhibit unconventional surface states and anomalous transport owing to unusual bulk electronic topology. In this study, we use photoemission spectroscopy and quantum transport to elucidate the topology of the room temperature magnet Co〈sub〉2〈/sub〉MnGa. We observe sharp bulk Weyl fermion line dispersions indicative of nontrivial topological invariants present in the magnetic phase. On the surface of the magnet, we observe electronic wave functions that take the form of drumheads, enabling us to directly visualize the crucial components of the bulk-boundary topological correspondence. By considering the Berry curvature field associated with the observed topological Weyl fermion lines, we quantitatively account for the giant anomalous Hall response observed in this magnet. Our experimental results suggest a rich interplay of strongly interacting electrons and topology in quantum matter.〈/p〉

Description: The advent of topological insulators (TIs), a novel class of materials that harbor a metallic spin-chiral surface state coexisting with band-insulating bulk, opens up new possibilities for spintronics. One promising route is current-induced switching of an adjacent magnetic layer via spin-orbit torque (SOT), arising from the large spin-orbit coupling intrinsically possessed by TIs. The Kondo insulator SmB 6 has been recently proposed to be a strongly correlated TI, supported by the observation of a metallic surface state in bulk SmB 6 , as evidenced by the thickness independence of the low-temperature resistance plateau. We report the synthesis of epitaxial (001) SmB 6 /Si thin films and a systematic thickness-dependent electrical transport study. Although the low-temperature resistance plateau is observed for all films from 50 to 500 nm in thickness, the resistance is distinctively thickness-dependent and does not support the notion of surface conduction and interior insulation. On the other hand, we demonstrate that SmB 6 can generate a large SOT to switch an adjacent ferromagnetic layer, even at room temperature. The effective SOT generated from SmB 6 is comparable to that from β-W, one of the strongest SOT materials.

Description: 〈p〉Long noncoding RNAs (lncRNAs) are important regulators of diverse biological processes; however, their function in macrophage activation is undefined. We describe a new regulatory mechanism, where an unreported lncRNA, 〈i〉PTPRE-AS1〈/i〉, targets receptor-type tyrosine protein phosphatase (PTPRE) to regulate macrophage activation. 〈i〉PTPRE-AS1〈/i〉 was selectively expressed in IL-4–stimulated macrophages, and its knockdown promoted M2 macrophage activation via MAPK/ERK 1/2 pathway. In vivo, 〈i〉PTPRE-AS1〈/i〉 deficiency enhanced IL-4–mediated M2 macrophage activation and accelerated pulmonary allergic inflammation while reducing chemical-induced colitis. Mechanistically, 〈i〉PTPRE-AS1〈/i〉 bound WDR5 directly, modulating H3K4me3 of the 〈i〉PTPRE〈/i〉 promoter to regulate 〈i〉PTPRE〈/i〉-dependent signaling during M2 macrophage activation. Further, the expression of 〈i〉PTPRE-AS1〈/i〉 and 〈i〉PTPRE〈/i〉 was significantly lower in peripheral blood mononuclear cells from patients with allergic asthma. These results provide evidence supporting the importance of 〈i〉PTPRE-AS1〈/i〉 in controlling macrophage function and the potential utility of 〈i〉PTPRE-AS1〈/i〉 as a target for controlling inflammatory diseases.〈/p〉