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Proceedings of the National Academy of Sciences of the United States of America

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https://www.readbyqxmd.com/read/28087691/imaging-proteins-at-the-single-molecule-level
#1
Jean-Nicolas Longchamp, Stephan Rauschenbach, Sabine Abb, Conrad Escher, Tatiana Latychevskaia, Klaus Kern, Hans-Werner Fink
Imaging single proteins has been a long-standing ambition for advancing various fields in natural science, as for instance structural biology, biophysics, and molecular nanotechnology. In particular, revealing the distinct conformations of an individual protein is of utmost importance. Here, we show the imaging of individual proteins and protein complexes by low-energy electron holography. Samples of individual proteins and protein complexes on ultraclean freestanding graphene were prepared by soft-landing electrospray ion beam deposition, which allows chemical- and conformational-specific selection and gentle deposition...
January 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28082725/tumor-suppression-by-p53-involves-inhibiting-an-enabler-fgf13
#2
James J Manfredi
No abstract text is available yet for this article.
January 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28082724/unplanned-ecological-engineering
#3
Ken H Andersen, Henrik Gislason
No abstract text is available yet for this article.
January 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28082723/presenilin-1-mutations-and-alzheimer-s-disease
#4
Raymond J Kelleher, Jie Shen
No abstract text is available yet for this article.
January 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28082722/inactivation-of-the-pbrm1-tumor-suppressor-gene-amplifies-the-hif-response-in-vhl-clear-cell-renal-carcinoma
#5
Wenhua Gao, Wei Li, Tengfei Xiao, Xiaole Shirley Liu, William G Kaelin
Most clear cell renal carcinomas (ccRCCs) are initiated by somatic inactivation of the VHL tumor suppressor gene. The VHL gene product, pVHL, is the substrate recognition unit of an ubiquitin ligase that targets the HIF transcription factor for proteasomal degradation; inappropriate expression of HIF target genes drives renal carcinogenesis. Loss of pVHL is not sufficient, however, to cause ccRCC. Additional cooperating genetic events, including intragenic mutations and copy number alterations, are required...
January 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28077456/revealing-nonclassicality-beyond-gaussian-states-via-a-single-marginal-distribution
#6
Jiyong Park, Yao Lu, Jaehak Lee, Yangchao Shen, Kuan Zhang, Shuaining Zhang, Muhammad Suhail Zubairy, Kihwan Kim, Hyunchul Nha
A standard method to obtain information on a quantum state is to measure marginal distributions along many different axes in phase space, which forms a basis of quantum-state tomography. We theoretically propose and experimentally demonstrate a general framework to manifest nonclassicality by observing a single marginal distribution only, which provides a unique insight into nonclassicality and a practical applicability to various quantum systems. Our approach maps the 1D marginal distribution into a factorized 2D distribution by multiplying the measured distribution or the vacuum-state distribution along an orthogonal axis...
January 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074042/different-clades-and-traits-yield-similar-grassland-functional-responses
#7
Elisabeth J Forrestel, Michael J Donoghue, Erika J Edwards, Walter Jetz, Justin C O du Toit, Melinda D Smith
Plant functional traits are viewed as key to predicting important ecosystem and community properties across resource gradients within and among biogeographic regions. Vegetation dynamics and ecosystem processes, such as aboveground net primary productivity (ANPP), are increasingly being modeled as a function of the quantitative traits of species, which are used as proxies for photosynthetic rates and nutrient and water-use efficiency. These approaches rely on an assumption that a certain trait value consistently confers a specific function or response under given environmental conditions...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074041/transcription-factor-xpp1-is-a-switch-between-primary-and-secondary-fungal-metabolism
#8
Christian Derntl, Bernhard Kluger, Christoph Bueschl, Rainer Schuhmacher, Robert L Mach, Astrid R Mach-Aigner
Fungi can produce a wide range of chemical compounds via secondary metabolism. These compounds are of major interest because of their (potential) application in medicine and biotechnology and as a potential source for new therapeutic agents and drug leads. However, under laboratory conditions, most secondary metabolism genes remain silent. This circumstance is an obstacle for the production of known metabolites and the discovery of new secondary metabolites. In this study, we describe the dual role of the transcription factor Xylanase promoter binding protein 1 (Xpp1) in the regulation of both primary and secondary metabolism of Trichoderma reesei Xpp1 was previously described as a repressor of xylanases...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074040/potent-neutralization-of-hepatitis-a-virus-reveals-a-receptor-mimic-mechanism-and-the-receptor-recognition-site
#9
Xiangxi Wang, Ling Zhu, Minghao Dang, Zhongyu Hu, Qiang Gao, Shuai Yuan, Yao Sun, Bo Zhang, Jingshan Ren, Abhay Kotecha, Thomas S Walter, Junzhi Wang, Elizabeth E Fry, David I Stuart, Zihe Rao
Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074039/cd34-mesenchymal-cells-are-a-major-component-of-the-intestinal-stem-cells-niche-at-homeostasis-and-after-injury
#10
Igor Stzepourginski, Giulia Nigro, Jean-Marie Jacob, Sophie Dulauroy, Philippe J Sansonetti, Gérard Eberl, Lucie Peduto
The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34(+) Gp38(+) αSMA(-) mesenchymal cells closely associated with Lgr5(+) IESCs. We demonstrate that CD34(+) Gp38(+) cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5(+) IESCs in intestinal organoids, an effect mainly mediated by Gremlin1...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074038/iconic-photographs-and-the-ebb-and-flow-of-empathic-response-to-humanitarian-disasters
#11
Paul Slovic, Daniel Västfjäll, Arvid Erlandsson, Robin Gregory
The power of visual imagery is well known, enshrined in such familiar sayings as "seeing is believing" and "a picture is worth a thousand words." Iconic photos stir our emotions and transform our perspectives about life and the world in which we live. On September 2, 2015, photographs of a young Syrian child, Aylan Kurdi, lying face-down on a Turkish beach, filled the front pages of newspapers worldwide. These images brought much-needed attention to the Syrian war that had resulted in hundreds of thousands of deaths and created millions of refugees...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074037/developmental-pruning-of-excitatory-synaptic-inputs-to-parvalbumin-interneurons-in-monkey-prefrontal-cortex
#12
Daniel W Chung, Zachary P Wills, Kenneth N Fish, David A Lewis
Working memory requires efficient excitatory drive to parvalbumin-positive (PV) interneurons in the primate dorsolateral prefrontal cortex (DLPFC). Developmental pruning eliminates superfluous excitatory inputs, suggesting that working memory maturation during adolescence requires pruning of excitatory inputs to PV interneurons. Therefore, we tested the hypothesis that excitatory synapses on PV interneurons are pruned during adolescence. The density of excitatory synapses, defined by overlapping vesicular glutamate transporter 1-positive (VGlut1+) and postsynaptic density 95-positive (PSD95+) puncta, on PV interneurons was lower in postpubertal relative to prepubertal monkeys...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074036/redox-crisis-underlies-conditional-light-dark-lethality-in-cyanobacterial-mutants-that-lack-the-circadian-regulator-rpaa
#13
Spencer Diamond, Benjamin E Rubin, Ryan K Shultzaberger, You Chen, Chase D Barber, Susan S Golden
Cyanobacteria evolved a robust circadian clock, which has a profound influence on fitness and metabolism under daily light-dark (LD) cycles. In the model cyanobacterium Synechococcus elongatus PCC 7942, a functional clock is not required for diurnal growth, but mutants defective for the response regulator that mediates transcriptional rhythms in the wild-type, regulator of phycobilisome association A (RpaA), cannot be cultured under LD conditions. We found that rpaA-null mutants are inviable after several hours in the dark and compared the metabolomes of wild-type and rpaA-null strains to identify the source of lethality...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074035/relevance-of-kondo-physics-for-the-temperature-dependence-of-the-bulk-modulus-in-plutonium
#14
LETTER
Marc Janoschek, Gerry Lander, Jon M Lawrence, E D Bauer, Jason C Lashley, Mark Lumsden, Douglas L Abernathy, J D Thompson
No abstract text is available yet for this article.
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074034/reply-to-janoschek-et-al-the-excited-%C3%AE-phase-of-plutonium
#15
Albert Migliori, Per Söderlind, Alexander Landa, Franz J Freibert, Boris Maiorov, B J Ramshaw, Jon B Betts
No abstract text is available yet for this article.
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069967/when-protected-areas-prove-insufficient-cheetah-and-protection-reliant-species
#16
Joshua R Ginsberg
No abstract text is available yet for this article.
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#17
Erika Della Mina, Alessandro Borghesi, Hao Zhou, Salim Bougarn, Sabri Boughorbel, Laura Israel, Ilaria Meloni, Maya Chrabieh, Yun Ling, Yuval Itan, Alessandra Renieri, Iolanda Mazzucchelli, Sabrina Basso, Piero Pavone, Raffaele Falsaperla, Roberto Ciccone, Rosa Maria Cerbo, Mauro Stronati, Capucine Picard, Orsetta Zuffardi, Laurent Abel, Damien Chaussabel, Nico Marr, Xiaoxia Li, Jean-Laurent Casanova, Anne Puel
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069965/dual-role-of-alcam-in-neuroinflammation-and-blood-brain-barrier-homeostasis
#18
Marc-André Lécuyer, Olivia Saint-Laurent, Lyne Bourbonnière, Sandra Larouche, Catherine Larochelle, Laure Michel, Marc Charabati, Michael Abadier, Stephanie Zandee, Neda Haghayegh Jahromi, Elizabeth Gowing, Camille Pittet, Ruth Lyck, Britta Engelhardt, Alexandre Prat
Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule found on blood-brain barrier endothelial cells (BBB-ECs) that was previously shown to be involved in leukocyte transmigration across the endothelium. In the present study, we found that ALCAM knockout (KO) mice developed a more severe myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE). The exacerbated disease was associated with a significant increase in the number of CNS-infiltrating proinflammatory leukocytes compared with WT controls...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069964/task-specific-reorganization-of-the-auditory-cortex-in-deaf-humans
#19
Łukasz Bola, Maria Zimmermann, Piotr Mostowski, Katarzyna Jednoróg, Artur Marchewka, Paweł Rutkowski, Marcin Szwed
The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069963/pathogen-boosted-adoptive-cell-transfer-immunotherapy-to-treat-solid-tumors
#20
Gang Xin, David M Schauder, Weiqing Jing, Aimin Jiang, Nikhil S Joshi, Bryon Johnson, Weiguo Cui
Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
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