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

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https://read.qxmd.com/read/31004064/visual-attention-is-not-limited-to-the-oculomotor-range
#1
Nina M Hanning, Martin Szinte, Heiner Deubel
Both patients with eye movement disorders and healthy participants whose oculomotor range had been experimentally reduced have been reported to show attentional deficits at locations unreachable by their eyes. Whereas previous studies were mainly based on the evaluation of reaction times, we measured visual sensitivity before saccadic eye movements and during fixation at locations either within or beyond participants' oculomotor range. Participants rotated their heads to prevent them from performing large rightward saccades...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004063/delta-secretase-cleaved-tau-antagonizes-trkb-neurotrophic-signalings-mediating-alzheimer-s-disease-pathologies
#2
Jie Xiang, Zhi-Hao Wang, Eun Hee Ahn, Xia Liu, Shan-Ping Yu, Fredric P Manfredsson, Ivette M Sandoval, Gong Ju, Shengxi Wu, Keqiang Ye
BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer's disease (AD). BDNF deficiency's association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004062/%C3%AE-sheet-secondary-structure-in-amyloid-%C3%AE-peptide-drives-aggregation-and-toxicity-in-alzheimer-s-disease
#3
Dylan Shea, Cheng-Chieh Hsu, Timothy M Bi, Natasha Paranjapye, Matthew Carter Childers, Joshua Cochran, Colson P Tomberlin, Libo Wang, Daniel Paris, Jeffrey Zonderman, Gabriele Varani, Christopher D Link, Mike Mullan, Valerie Daggett
Alzheimer's disease (AD) is characterized by the deposition of β-sheet-rich, insoluble amyloid β-peptide (Aβ) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aβ oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aβ-associated cytotoxicity peaks, en route to forming nontoxic β-sheet fibrils...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004061/data-gaps-and-opportunities-for-comparative-and-conservation-biology
#4
Dalia A Conde, Johanna Staerk, Fernando Colchero, Rita da Silva, Jonas Schöley, H Maria Baden, Lionel Jouvet, John E Fa, Hassan Syed, Eelke Jongejans, Shai Meiri, Jean-Michel Gaillard, Scott Chamberlain, Jonathan Wilcken, Owen R Jones, Johan P Dahlgren, Ulrich K Steiner, Lucie M Bland, Ivan Gomez-Mestre, Jean-Dominique Lebreton, Jaime González Vargas, Nate Flesness, Vladimir Canudas-Romo, Roberto Salguero-Gómez, Onnie Byers, Thomas Bjørneboe Berg, Alexander Scheuerlein, Sébastien Devillard, Dmitry S Schigel, Oliver A Ryder, Hugh P Possingham, Annette Baudisch, James W Vaupel
Biodiversity loss is a major challenge. Over the past century, the average rate of vertebrate extinction has been about 100-fold higher than the estimated background rate and population declines continue to increase globally. Birth and death rates determine the pace of population increase or decline, thus driving the expansion or extinction of a species. Design of species conservation policies hence depends on demographic data (e.g., for extinction risk assessments or estimation of harvesting quotas). However, an overview of the accessible data, even for better known taxa, is lacking...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004060/component-of-splicing-factor-sf3b-plays-a-key-role-in-translational-control-of-polyribosomes-on-the-endoplasmic-reticulum
#5
Tomonori Ueno, Yuki Taga, Rei Yoshimoto, Akila Mayeda, Shunji Hattori, Kiyoko Ogawa-Goto
One of the morphological hallmarks of terminally differentiated secretory cells is highly proliferated membrane of the rough endoplasmic reticulum (ER), but the molecular basis for the high rate of protein biosynthesis in these cells remains poorly documented. An important aspect of ER translational control is the molecular mechanism that supports efficient use of targeted mRNAs in polyribosomes. Here, we identify an enhancement system for ER translation promoted by p180, an integral ER membrane protein we previously reported as an essential factor for the assembly of ER polyribosomes...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004059/unifying-photocycle-model-for-light-adaptation-and-temporal-evolution-of-cation-conductance-in-channelrhodopsin-2
#6
Jens Kuhne, Johannes Vierock, Stefan Alexander Tennigkeit, Max-Aylmer Dreier, Jonas Wietek, Dennis Petersen, Konstantin Gavriljuk, Samir F El-Mashtoly, Peter Hegemann, Klaus Gerwert
Although channelrhodopsin (ChR) is a widely applied light-activated ion channel, important properties such as light adaptation, photocurrent inactivation, and alteration of the ion selectivity during continuous illumination are not well understood from a molecular perspective. Herein, we address these open questions using single-turnover electrophysiology, time-resolved step-scan FTIR, and Raman spectroscopy of fully dark-adapted ChR2. This yields a unifying parallel photocycle model integrating now all so far controversial discussed data...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004058/sideways-and-stable-crack-propagation-in-a-silicone-elastomer
#7
Seunghyun Lee, Matt Pharr
We have discovered a peculiar form of fracture that occurs in a highly stretchable silicone elastomer (Smooth-On Ecoflex 00-30). Under certain conditions, cracks propagate in a direction perpendicular to the initial precut and in the direction of the applied load. In other words, the crack deviates from the standard trajectory and instead propagates perpendicular to that trajectory. The crack arrests stably, and thus the material ahead of the crack front continues to sustain load, thereby enabling enormous stretchabilities...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004057/three-dimensional-architecture-of-epithelial-primary-cilia
#8
Shufeng Sun, Rebecca L Fisher, Samuel S Bowser, Brian T Pentecost, Haixin Sui
We report a complete 3D structural model of typical epithelial primary cilia based on structural maps of full-length primary cilia obtained by serial section electron tomography. Our data demonstrate the architecture of primary cilia differs extensively from the commonly acknowledged 9+0 paradigm. The axoneme structure is relatively stable but gradually evolves from base to tip with a decreasing number of microtubule complexes (MtCs) and a reducing diameter. The axonemal MtCs are cross-linked by previously unrecognized fibrous protein networks...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004056/expeditious-scalable-solution-growth-of-metal-oxide-films-by-combustion-blade-coating-for-flexible-electronics
#9
Binghao Wang, Peijun Guo, Li Zeng, Xia Yu, Aritra Sil, Wei Huang, Matthew J Leonardi, Xinan Zhang, Gang Wang, Shaofeng Lu, Zhihua Chen, Michael J Bedzyk, Richard D Schaller, Tobin J Marks, Antonio Facchetti
Metal oxide (MO) semiconductor thin films prepared from solution typically require multiple hours of thermal annealing to achieve optimal lattice densification, efficient charge transport, and stable device operation, presenting a major barrier to roll-to-roll manufacturing. Here, we report a highly efficient, cofuel-assisted scalable combustion blade-coating (CBC) process for MO film growth, which involves introducing both a fluorinated fuel and a preannealing step to remove deleterious organic contaminants and promote complete combustion...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004055/large-bandgap-of-pressurized-trilayer-graphene
#10
Feng Ke, Yabin Chen, Ketao Yin, Jiejuan Yan, Hengzhong Zhang, Zhenxian Liu, John S Tse, Junqiao Wu, Ho-Kwang Mao, Bin Chen
Graphene-based nanodevices have been developed rapidly and are now considered a strong contender for postsilicon electronics. However, one challenge facing graphene-based transistors is opening a sizable bandgap in graphene. The largest bandgap achieved so far is several hundred meV in bilayer graphene, but this value is still far below the threshold for practical applications. Through in situ electrical measurements, we observed a semiconducting character in compressed trilayer graphene by tuning the interlayer interaction with pressure...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004054/alarmone-ap4a-is-elevated-by-aminoglycoside-antibiotics-and-enhances-their-bactericidal-activity
#11
Xia Ji, Jin Zou, Haibo Peng, Anne-Sophie Stolle, Ruiqiang Xie, Hongjie Zhang, Bo Peng, John J Mekalanos, Jun Zheng
Second messenger molecules play important roles in the responses to various stimuli that can determine a cell's fate under stress conditions. Here, we report that lethal concentrations of aminoglycoside antibiotics result in the production of a dinucleotide alarmone metabolite-diadenosine tetraphosphate (Ap4A), which promotes bacterial cell killing by this class of antibiotics. We show that the treatment of Escherichia coli with lethal concentrations of kanamycin (Kan) dramatically increases the production of Ap4A...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004053/new-age-for-progressive-multiple-sclerosis
#12
Jaime Imitola
No abstract text is available yet for this article.
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004052/hydrogen-bonding-steers-the-product-selectivity-of-electrocatalytic-co-reduction
#13
Jingyi Li, Xiang Li, Charuni M Gunathunge, Matthias M Waegele
The product selectivity of many heterogeneous electrocatalytic processes is profoundly affected by the liquid side of the electrocatalytic interface. The electrocatalytic reduction of CO to hydrocarbons on Cu electrodes is a prototypical example of such a process. However, probing the interactions of surface-bound intermediates with their liquid reaction environment poses a formidable experimental challenge. As a result, the molecular origins of the dependence of the product selectivity on the characteristics of the electrolyte are still poorly understood...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004051/cortical-patterning-of-abnormal-morphometric-similarity-in-psychosis-is-associated-with-brain-expression-of-schizophrenia-related-genes
#14
Sarah E Morgan, Jakob Seidlitz, Kirstie J Whitaker, Rafael Romero-Garcia, Nicholas E Clifton, Cristina Scarpazza, Therese van Amelsvoort, Machteld Marcelis, Jim van Os, Gary Donohoe, David Mothersill, Aiden Corvin, Andrew Pocklington, Armin Raznahan, Philip McGuire, Petra E Vértes, Edward T Bullmore
Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004050/mapk-pathway-and-b-cells-overactivation-in-multiple-sclerosis-revealed-by-phosphoproteomics-and-genomic-analysis
#15
Ekaterina Kotelnikova, Narsis A Kiani, Dimitris Messinis, Inna Pertsovskaya, Vicky Pliaka, Marti Bernardo-Faura, Melanie Rinas, Gemma Vila, Irati Zubizarreta, Irene Pulido-Valdeolivas, Theodore Sakellaropoulos, Wolfgang Faigle, Gilad Silberberg, Mar Masso, Pernilla Stridh, Janina Behrens, Tomas Olsson, Roland Martin, Friedemann Paul, Leonidas G Alexopoulos, Julio Saez-Rodriguez, Jesper Tegner, Pablo Villoslada
Dysregulation of signaling pathways in multiple sclerosis (MS) can be analyzed by phosphoproteomics in peripheral blood mononuclear cells (PBMCs). We performed in vitro kinetic assays on PBMCs in 195 MS patients and 60 matched controls and quantified the phosphorylation of 17 kinases using xMAP assays. Phosphoprotein levels were tested for association with genetic susceptibility by typing 112 single-nucleotide polymorphisms (SNPs) associated with MS susceptibility. We found increased phosphorylation of MP2K1 in MS patients relative to the controls...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31004049/signatures-of-slip-in-dewetting-polymer-films
#16
Dirk Peschka, Sabrina Haefner, Ludovic Marquant, Karin Jacobs, Andreas Münch, Barbara Wagner
Thin polymer films on hydrophobic substrates are susceptible to rupture and hole formation. This, in turn, initiates a complex dewetting process, which ultimately leads to characteristic droplet patterns. Experimental and theoretical studies suggest that the type of droplet pattern depends on the specific interfacial condition between the polymer and the substrate. Predicting the morphological evolution over long timescales and on the different length scales involved is a major computational challenge. In this study, a highly adaptive numerical scheme is presented, which allows for following the dewetting process deep into the nonlinear regime of the model equations and captures the complex dynamics, including the shedding of droplets...
April 19, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31000603/transcription-factors-irf8-and-pu-1-are-required-for-follicular-b-cell-development-and-bcl6-driven-germinal-center-responses
#17
Hongsheng Wang, Shweta Jain, Peng Li, Jian-Xin Lin, Jangsuk Oh, Chenfeng Qi, Yuanyuan Gao, Jiafang Sun, Tomomi Sakai, Zohreh Naghashfar, Sadia Abbasi, Alexander L Kovalchuk, Silvia Bolland, Stephen L Nutt, Warren J Leonard, Herbert C Morse
The IRF and Ets families of transcription factors regulate the expression of a range of genes involved in immune cell development and function. However, the understanding of the molecular mechanisms of each family member has been limited due to their redundancy and broad effects on multiple lineages of cells. Here, we report that double deletion of floxed Irf8 and Spi1 (encoding PU.1) by Mb1-Cre (designated DKO mice) in the B cell lineage resulted in severe defects in the development of follicular and germinal center (GC) B cells...
April 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31000602/rnai-expression-tuning-microfluidic-screening-and-genome-recombineering-for-improved-protein-production-in-saccharomyces-cerevisiae
#18
Guokun Wang, Sara M Björk, Mingtao Huang, Quanli Liu, Kate Campbell, Jens Nielsen, Haakan N Joensson, Dina Petranovic
The cellular machinery that supports protein synthesis and secretion lies at the foundation of cell factory-centered protein production. Due to the complexity of such cellular machinery, the challenge in generating a superior cell factory is to fully exploit the production potential by finding beneficial targets for optimized strains, which ideally could be used for improved secretion of other proteins. We focused on an approach in the yeast Saccharomyces cerevisiae that allows for attenuation of gene expression, using RNAi combined with high-throughput microfluidic single-cell screening for cells with improved protein secretion...
April 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31000601/dna-demethylation-by-ros1a-in-rice-vegetative-cells-promotes-methylation-in-sperm
#19
M Yvonne Kim, Akemi Ono, Stefan Scholten, Tetsu Kinoshita, Daniel Zilberman, Takashi Okamoto, Robert L Fischer
Epigenetic reprogramming is required for proper regulation of gene expression in eukaryotic organisms. In Arabidopsis , active DNA demethylation is crucial for seed viability, pollen function, and successful reproduction. The DEMETER (DME) DNA glycosylase initiates localized DNA demethylation in vegetative and central cells, so-called companion cells that are adjacent to sperm and egg gametes, respectively. In rice, the central cell genome displays local DNA hypomethylation, suggesting that active DNA demethylation also occurs in rice; however, the enzyme responsible for this process is unknown...
April 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31000600/hippo-signaling-is-intrinsically-regulated-during-cell-cycle-progression-by-apc-c-cdh1
#20
Wantae Kim, Yong Suk Cho, Xiaohui Wang, Ogyi Park, Xueyan Ma, Hanjun Kim, Wenjian Gan, Eek-Hoon Jho, Boksik Cha, Yun-Ji Jeung, Lei Zhang, Bin Gao, Wenyi Wei, Jin Jiang, Kyung-Sook Chung, Yingzi Yang
The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration and its dysregulation is widely implicated in various cancers. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, large tumor suppressor (LATS) kinases and YAP/TAZ transcription factors, oscillate during mitotic cell cycle. We further identified that the anaphase-promoting complex/cyclosome (APC/C)Cdh1 E3 ubiquitin ligase complex, which plays a key role governing eukaryotic cell cycle progression, intrinsically regulates Hippo signaling activities...
April 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
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