1080PA new population model validated pharmacokinetic similarity of HLX01 and rituximab in B-cell lymphoma
The objective of this study was to develop a reliable population pharmacokinetic (PopPK) model of rituximab in patients with RA, the most appropriate patient population for PK evaluation, and validate HLX01 and CN-RTX PK data in patients with DLBCL.MethodsA PK model for HLX01 and the EU-RTX from a randomised, double-blind phase 1/2 study (NCT03355872) in 196 RA patients (serum sample n  = 4289) was developed using non-linear mixed-effect modeling (NONMEM®) with the first-order conditional estimation with interaction (FOCEI) method. PK and PK-pharmacodynamic relationship were characterised with various cov...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

Occupational Medicine Calendar
2019DateEventContact AddressVenueNovember 2-6APHA Annual Meeting& Expo Sponsor: American Public Health Associationhttps://apha.org/events-and-meetings/apha-calendar/2019/apha-annual-meeting-and-expoPhiladelphia, USANovember 2-612th European Public Health Conferencehttps://ephconference.eu/marseille-2019:-building-bridges-for-solidarity-and-public-%20health-95Marseille, FranceNovember 12Central England Occupational Health Group Annual Conferencehttps://ceohg.org.uk/events/ceohg-conference-2019/Redditch, Worcestershire2020DateEventContact AddressVenueJanuary 28-February 1International Conclave on Occupational Healthhttp:...
Source: Occupational Medicine - October 1, 2019 Category: Respiratory Medicine Source Type: research

The Chinese Academy of Sciences at 70
Nature, Published online: 01 October 2019; doi:10.1038/d41586-019-02950-5Over the past few decades, the academy’s investments have made it one of the world’s richest. Could its financial autonomy be a model for others? (Source: Nature AOP)
Source: Nature AOP - October 1, 2019 Category: Research Source Type: research

In This Issue [This Week in PNAS]
Body representation in monkeys’ brains Rhesus macaque (Macaca mulatta). Image courtesy of Pixabay/RobbieRoss. A sense of ownership of one’s own body is a central element of self-consciousness. The psychological and neurological mechanisms underlying this sense can be investigated through illusions, such as the rubber-hand illusion, in which a person perceives... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Tags: In This Issue This Week in PNAS Source Type: research

Effect of alder on soil bacteria offers an alternative explanation to the role played by alder in rock weathering [Biological Sciences]
The article by Perakis and Pett-Ridge in PNAS (1) stimulated an interesting discussion (2) on the role of nitrogen-fixing alder in enhancing rock weathering and supply of rock-derived nutrients. The authors ascribe the accelerated rate of weathering to the generation of acidic conditions in the soil due to excess nitrogen... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Mayank Krishna, Saurabh Kumar Singh, Jayant K. Tripathi, Rupesh Chaturvedi, Satish Chandra Garkoti Tags: Letters, Front Matter-Letters-Set Free Source Type: research

Reply to Krishna et al.: Resolving age-related changes in nitrogen fixation and mineral weathering by Alnus tree species [Biological Sciences]
In PNAS we report that the symbiotic nitrogen-fixing tree red alder (Alnus rubra) accesses more rock-derived nutrients than nonfixing trees (1). We further hypothesize that excess nitrogen fixation by alder, leading to high rates of nitrification and nitric acid generation in soil, could accelerate mineral weathering (1, 2). Krishna et... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Steven S. Perakis, Julie C. Pett-Ridge Tags: Letters, Front Matter-Letters-Set Free Source Type: research

On the origin of a pathogenic HERV-W envelope protein present in multiple sclerosis lesions [Biological Sciences]
We read with great interest the recent article by Kremer et al. showing that an envelope (ENV) protein encoded by human endogenous retrovirus type W (HERV-W) is present in myeloid cells in multiple sclerosis (MS) lesions, as detected by mouse monoclonal antibody GN-mAB_03 (3B2H4) directed against HERV-W ENV (1). Furthermore,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Klemens Ruprecht, Jens Mayer Tags: Letters, Front Matter-Letters-Set Free Source Type: research

Reply to Ruprecht and Mayer: Unearthing genomic fossils in the pathogenesis of multiple sclerosis [Biological Sciences]
This Reply refers to the Letter by Ruprecht and Mayer titled “On the origin of a pathogenic HERV-W envelope protein present in multiple sclerosis lesions” (1). In their Letter, the authors confirm the specificity of the monoclonal antibody GN-MAb_03 (3B2H4) that we used to detect the pHERV-W ENV protein in... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: David Kremer, Herve Perron, Patrick Kury Tags: Letters, Front Matter-Letters-Set Free Source Type: research

Inside-out signaling through FAK-integrin axis may regulate circulating cancer cell metastatic adhesion [Biological Sciences]
In PNAS, Chang et al. (1) call attention to the function of focal adhesion kinase (FAK) in mediating inside-out signaling regulating immune cell adhesion to the endothelium by elegantly studying the FAK–RAP1–RIAM–talin pathway for feedforward inside-out signaling through integrin described by Lagarrigue (2). Chang et al. solve the crystal structure... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Christina Downey-Biechler, David H. Craig, Shyam K. More, Marc D. Basson Tags: Letters, Front Matter-Letters-Set Free Source Type: research

Understanding the industrial contribution to pollution offers opportunities to further improve air quality in the United States [Environmental Sciences]
The quality of the air in the United States has improved substantially (1). The risks, however, remain high for several populations, and there is still much to learn about the sources and impacts of air pollution. Increasing our understanding of the sources of environmental damage can help us design policies... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Juan Moreno-Cruz Tags: Commentaries Source Type: research

Premotor cortex implements causal inference in multisensory own-body perception [Neuroscience]
How do we come to experience our body as our own? When we look at our hands, for example, we immediately sense that they are part of our body. This experience of the limbs and other body parts being one’s own is referred to as the sense of “body ownership”... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: H. Henrik Ehrsson, Marie Chancel Tags: Commentaries Source Type: research

Physiological signaling in the absence of amidated peptides [Neuroscience]
Peptidergic signaling is an ancient manner of intertissue communication in multicellular organisms. Even the early eukaryote Trichoplax, with its limited 6-tissue repertoire, uses peptides to communicate between its tissues (1). Humans use peptidergic communication not only to transfer signals between tissues, but also to employ peptide signals in brain and... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Iris Lindberg, Christopher C. Glembotski Tags: Commentaries Source Type: research

Genomic analysis of siderophore {beta}-hydroxylases reveals divergent stereocontrol and expands the condensation domain family [Chemistry]
Genome mining of biosynthetic pathways streamlines discovery of secondary metabolites but can leave ambiguities in the predicted structures, which must be rectified experimentally. Through coupling the reactivity predicted by biosynthetic gene clusters with verified structures, the origin of the β-hydroxyaspartic acid diastereomers in siderophores is reported herein. Two functional subtypes... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Zachary L. Reitz, Clifford D. Hardy, Jaewon Suk, Jean Bouvet, Alison Butler Tags: PNAS Plus Source Type: research

Quantifying stochastic uncertainty in detection time of human-caused climate signals [Earth, Atmospheric, and Planetary Sciences]
Large initial condition ensembles of a climate model simulation provide many different realizations of internal variability noise superimposed on an externally forced signal. They have been used to estimate signal emergence time at individual grid points, but are rarely employed to identify global fingerprints of human influence. Here we analyze... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Benȷamin D. Santer, John C. Fyfe, Susan Solomon, Jeffrey F. Painter, Celine Bonfils, Giuliana Pallotta, Mark D. Zelinka Tags: PNAS Plus Source Type: research

High-resolution limited-angle phase tomography of dense layered objects using deep neural networks [Engineering]
We present a machine learning-based method for tomographic reconstruction of dense layered objects, with range of projection angles limited to ±10○. Whereas previous approaches to phase tomography generally require 2 steps, first to retrieve phase projections from intensity projections and then to perform tomographic reconstruction on the retrieved phase projections,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Alexandre Goy, Girish Rughoobur, Shuai Li, Kwabena Arthur, Akintunde I. Akinwande, George Barbastathis Tags: PNAS Plus Source Type: research

A network of phosphatidylinositol 4,5-bisphosphate binding sites regulates gating of the Ca2+-activated Cl- channel ANO1 (TMEM16A) [Biophysics and Computational Biology]
ANO1 (TMEM16A) is a Ca2+-activated Cl− channel that regulates diverse cellular functions including fluid secretion, neuronal excitability, and smooth muscle contraction. ANO1 is activated by elevation of cytosolic Ca2+ and modulated by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Here, we describe a closely concerted experimental and computational study, including electrophysiology, mutagenesis, functional assays,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Kuai Yu, Tao Jiang, YuanYuan Cui, Emad Tajkhorshid, H. Criss Hartzell Tags: PNAS Plus Source Type: research

Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR [Biophysics and Computational Biology]
QacR, a multidrug-binding transcriptional repressor in pathogenic bacteria Staphylococcus aureus, modulates the transcriptional level of the multidrug transporter gene, qacA, in response to engaging a set of diverse ligands. However, the structural basis that defines the variable induction level remains unknown. Here, we reveal that the conformational equilibrium between the... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Koh Takeuchi, Misaki Imai, Ichio Shimada Tags: PNAS Plus Source Type: research

Structural basis of molecular logic OR in a dual-sensor histidine kinase [Biophysics and Computational Biology]
Signal detection and integration by sensory proteins constitute the critical molecular events as living organisms respond to changes in a complex environment. Many sensory proteins adopt a modular architecture that integrates the perception of distinct chemical or physical signals and the generation of a biological response in the same protein... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Heewhan Shin, Zhong Ren, Xiaoli Zeng, Sepalika Bandara, Xiaojing Yang Tags: PNAS Plus Source Type: research

Global invasion history of the agricultural pest butterfly Pieris rapae revealed with genomics and citizen science [Evolution]
The small cabbage white butterfly, Pieris rapae, is a major agricultural pest of cruciferous crops and has been introduced to every continent except South America and Antarctica as a result of human activities. In an effort to reconstruct the near-global invasion history of P. rapae, we developed a citizen science... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Sean F. Ryan, Eric Lombaert, Anne Espeset, Roger Vila, Gerard Talavera, Vlad Dincă, Meredith M. Doellman, Mark A. Renshaw, Matthew W. Eng, Emily A. Hornett, Yiyuan Li, Michael E. Pfrender, DeWayne Shoemaker Tags: PNAS Plus Source Type: research

Microbiome composition shapes rapid genomic adaptation of Drosophila melanogaster [Evolution]
Population genomic data has revealed patterns of genetic variation associated with adaptation in many taxa. Yet understanding the adaptive process that drives such patterns is challenging; it requires disentangling the ecological agents of selection, determining the relevant timescales over which evolution occurs, and elucidating the genetic architecture of adaptation. Doing... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Seth M. Rudman, Sharon Greenblum, Rachel C. Hughes, Subhash Rajpurohit, Ozan Kiratli, Dallin B. Lowder, Skyler G. Lemmon, Dmitri A. Petrov, John M. Chaston, Paul Schmidt Tags: PNAS Plus Source Type: research

Monitoring of switches in heterochromatin-induced silencing shows incomplete establishment and developmental instabilities [Genetics]
Position effect variegation (PEV) in Drosophila results from new juxtapositions of euchromatic and heterochromatic chromosomal regions, and manifests as striking bimodal patterns of gene expression. The semirandom patterns of PEV, reflecting clonal relationships between cells, have been interpreted as gene-expression states that are set in development and thereafter maintained without... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Farah Bughio, Gary R. Huckell, Keith A. Maggert Tags: PNAS Plus Source Type: research

The circadian clock of CD8 T cells modulates their early response to vaccination and the rhythmicity of related signaling pathways [Immunology and Inflammation]
Circadian variations of various aspects of the immune system have been described. However, the circadian control of T cells has been relatively unexplored. Here, we investigated the role of circadian clocks in regulating CD8 T cell response to antigen presentation by dendritic cells (DCs). The in vivo CD8 T cell... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Chloe C. Nobis, Genevieve Dubeau Laramee, Laura Kervezee, Dave Maurice De Sousa, Nathalie Labrecque, Nicolas Cermakian Tags: PNAS Plus Source Type: research

Genetic variation of DNA methyltransferase-3A contributes to protection against persistent MRSA bacteremia in patients [Immunology and Inflammation]
The role of the host in development of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not well understood. A cohort of prospectively enrolled patients with persistent methicillin-resistant S. aureus bacteremia (PB) and resolving methicillin-resistant S. aureus bacteremia (RB) matched by sex, age, race, hemodialysis status, diabetes mellitus, and presence of... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Felix Mba Medie, Batu K. Sharma-Kuinkel, Felicia Ruffin, Liana C. Chan, Maura Rossetti, Yu-Ling Chang, Lawrence P. Park, Arnold S. Bayer, Scott G. Filler, Richard Ahn, Elaine F. Reed, David Gjertson, Michael R. Yeaman, Vance G. Fowler Jr., the MRSA Syste Tags: PNAS Plus Source Type: research

Conversion of Sox2-dependent Merkel cell carcinoma to a differentiated neuron-like phenotype by T antigen inhibition [Medical Sciences]
Viral cancers show oncogene addiction to viral oncoproteins, which are required for survival and proliferation of the dedifferentiated cancer cell. Human Merkel cell carcinomas (MCCs) that harbor a clonally integrated Merkel cell polyomavirus (MCV) genome have low mutation burden and require viral T antigen expression for tumor growth. Here, we... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Alexis Harold, Yutaka Amako, Junichi Hachisuka, Yulong Bai, Meng Yen Li, Linda Kubat, Jan Gravemeyer, Jonathan Franks, Julia R. Gibbs, Hyun Jung Park, Elena Ezhkova, Jurgen C. Becker, Masahiro Shuda Tags: PNAS Plus Source Type: research

Spatial organization of RNA polymerase and its relationship with transcription in Escherichia coli [Microbiology]
Recent studies have shown that RNA polymerase (RNAP) is organized into distinct clusters in Escherichia coli and Bacillus subtilis cells. Spatially organized molecular components in prokaryotic systems imply compartmentalization without the use of membranes, which may offer insights into unique functions and regulations. It has been proposed that the formation... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Xiaoli Weng, Christopher H. Bohrer, Kelsey Bettridge, Arvin Cesar Lagda, Cedric Cagliero, Ding Jun Jin, Jie Xiao Tags: PNAS Plus Source Type: research

{alpha}v{beta}3-integrin regulates PD-L1 expression and is involved in cancer immune evasion [Microbiology]
Tumors utilize a number of effective strategies, including the programmed death 1/PD ligand 1 (PD-1/PD-L1) axis, to evade immune-mediated control of their growth. PD-L1 expression is mainly induced by IFN receptor signaling or constitutively induced. Integrins are an abundantly expressed class of proteins which play multiple deleterious roles in cancer... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Andrea Vannini, Valerio Leoni, Catia Barboni, Mara Sanapo, Anna Zaghini, Paolo Malatesta, Gabriella Campadelli-Fiume, Tatiana Gianni Tags: PNAS Plus Source Type: research

Identifying roles for peptidergic signaling in mice [Neuroscience]
Despite accumulating evidence demonstrating the essential roles played by neuropeptides, it has proven challenging to use this information to develop therapeutic strategies. Peptidergic signaling can involve juxtacrine, paracrine, endocrine, and neuronal signaling, making it difficult to define physiologically important pathways. One of the final steps in the biosynthesis of many... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Kathryn G. Powers, Xin-Ming Ma, Betty A. Eipper, Richard E. Mains Tags: PNAS Plus Source Type: research

Cell class-specific modulation of attentional signals by acetylcholine in macaque frontal eye field [Neuroscience]
Attention is critical to high-level cognition, and attentional deficits are a hallmark of cognitive dysfunction. A key transmitter for attentional control is acetylcholine, but its cellular actions in attention-controlling areas remain poorly understood. Here we delineate how muscarinic and nicotinic receptors affect basic neuronal excitability and attentional control signals in... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Miguel Dasilva, Christian Brandt, Sascha Gotthardt, Marc Alwin Gieselmann, Claudia Distler, Alexander Thiele Tags: PNAS Plus Source Type: research

Maternal viral infection causes global alterations in porcine fetal microglia [Neuroscience]
Maternal infections during pregnancy are associated with increased risk of neurodevelopmental disorders, although the precise mechanisms remain to be elucidated. Previously, we established a maternal immune activation (MIA) model using swine, which results in altered social behaviors of piglet offspring. These behavioral abnormalities occurred in the absence of microglia priming.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Adrienne M. Antonson, Marcus A. Lawson, Megan P. Caputo, Stephanie M. Matt, Brian J. Leyshon, Rodney W. Johnson Tags: PNAS Plus Source Type: research

Ca2+-independent but voltage-dependent quantal catecholamine secretion (CiVDS) in the mammalian sympathetic nervous system [Neuroscience]
Action potential-induced vesicular exocytosis is considered exclusively Ca2+ dependent in Katz’s Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Rong Huang, Yuan Wang, Jie Li, Xiaohan Jiang, Yinglin Li, Bing Liu, Xi Wu, Xingyu Du, Yuqi Hang, Mu Jin, Feipeng Zhu, Changhe Wang, Zuying Chai, Zhuan Zhou Tags: PNAS Plus Source Type: research

Discordance between eNOS phosphorylation and activation revealed by multispectral imaging and chemogenetic methods [Pharmacology]
Nitric oxide (NO) synthesized by the endothelial isoform of nitric oxide synthase (eNOS) is a critical determinant of vascular homeostasis. However, the real-time detection of intracellular NO—a free radical gas—has been difficult, and surrogate markers for eNOS activation are widely utilized. eNOS phosphorylation can be easily measured in cells by... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Emrah Eroglu, Seyed Soheil Saeedi Saravi, Andrea Sorrentino, Benjamin Steinhorn, Thomas Michel Tags: PNAS Plus Source Type: research

Structural basis for power stroke vs. Brownian ratchet mechanisms of motor proteins [Biophysics and Computational Biology]
Two mechanisms have been proposed for the function of motor proteins: The power stroke and the Brownian ratchet. The former refers to generation of a large downhill free energy gradient over which the motor protein moves nearly irreversibly in making a step, whereas the latter refers to biasing or rectifying... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Wonmuk Hwang, Martin Karplus Tags: Perspective Source Type: research

Selection of endurance capabilities and the trade-off between pressure and volume in the evolution of the human heart [Anthropology]
Chimpanzees and gorillas, when not inactive, engage primarily in short bursts of resistance physical activity (RPA), such as climbing and fighting, that creates pressure stress on the cardiovascular system. In contrast, to initially hunt and gather and later to farm, it is thought that preindustrial human survival was dependent on... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Robert E. Shave, Daniel E. Lieberman, Aimee L. Drane, Marcel G. Brown, Alan M. Batterham, Steven Worthington, Rebeca Atencia, Yedra Feltrer, Jennifer Neary, Rory B. Weiner, Meagan M. Wasfy, Aaron L. Baggish Tags: Biological Sciences Source Type: research

Inner Workings: Dwarf galaxies pose new questions about dark matter and the early universe that models are struggling to answer [Astronomy]
Late one night in October 2015, Andrew Wetzel was fretting. For 15 days, his cosmological models had been swirling virtual dark matter around cybernetic gas and dust and slowly generating a synthetic galaxy approximately the size of our own Milky Way, and Wetzel was about to receive the results. “I... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Adam Mann Tags: Inner Workings, Front Matter Source Type: research

A higher-order configuration of the heterodimeric DOT1L-AF10 coiled-coil domains potentiates their leukemogenenic activity [Biochemistry]
Chromosomal translocations of MLL1 (Mixed Lineage Leukemia 1) yield oncogenic chimeric proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1–AF10 fusion causes leukemia through recruiting the H3K79 histone methyltransferase DOT1L via AF10’s octapeptide and leucine zipper (OM-LZ) motifs. Yet, the precise interaction sites in DOT1L, detailed... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Xiaosheng Song, Liuliu Yang, Mingzhu Wang, Yue Gu, Buqing Ye, Zusen Fan, Rui-Ming Xu, Na Yang Tags: Biological Sciences Source Type: research

Redox-dependent gating of VDAC by mitoNEET [Biophysics and Computational Biology]
MitoNEET is an outer mitochondrial membrane protein essential for sensing and regulation of iron and reactive oxygen species (ROS) homeostasis. It is a key player in multiple human maladies including diabetes, cancer, neurodegeneration, and Parkinson’s diseases. In healthy cells, mitoNEET receives its clusters from the mitochondrion and transfers them to... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Colin H. Lipper, Jason T. Stofleth, Fang Bai, Yang–Sung Sohn, Susmita Roy, Ron Mittler, Rachel Nechushtai, Jose N. Onuchic, Patricia A. Jennings Tags: Biological Sciences Source Type: research

Tubulin lattice in cilia is in a stressed form regulated by microtubule inner proteins [Biophysics and Computational Biology]
In this study, we present a near-atomic resolution map of the Tetrahymena doublet microtubule by cryoelectron microscopy. The map demonstrates that the network of microtubule inner... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Muneyoshi Ichikawa, Ahmad Abdelzaher Zaki Khalifa, Shintaroh Kubo, Daniel Dai, Kaustuv Basu, Mohammad Amin Faghfor Maghrebi, Javier Vargas, Khanh Huy Bui Tags: Biological Sciences Source Type: research

Organization of fast and slow chromatin revealed by single-nucleosome dynamics [Biophysics and Computational Biology]
In this study, we investigate chromatin dynamics by statistically analyzing single-nucleosome movement in living human cells. Bimodal nature of the mean square displacement distribution of nucleosomes allows for a natural categorization of the nucleosomes as fast and... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: S. S. Ashwin, Tadasu Nozaki, Kazuhiro Maeshima, Masaki Sasai Tags: Biological Sciences Source Type: research

Monomeric structure of an active form of bovine cytochrome c oxidase [Biophysics and Computational Biology]
Cytochrome c oxidase (CcO), a membrane enzyme in the respiratory chain, catalyzes oxygen reduction by coupling electron and proton transfer through the enzyme with a proton pump across the membrane. In all crystals reported to date, bovine CcO exists as a dimer with the same intermonomer contacts, whereas CcOs and... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Kyoko Shinzawa-Itoh, Takashi Sugimura, Tomonori Misaki, Yoshiki Tadehara, Shogo Yamamoto, Makoto Hanada, Naomine Yano, Tetsuya Nakagawa, Shigefumi Uene, Takara Yamada, Hiroshi Aoyama, Eiki Yamashita, Tomitake Tsukihara, Shinya Yoshikawa, Kazumasa Muramoto Tags: Biological Sciences Source Type: research

Force-induced recruitment of cten along keratin network in epithelial cells [Cell Biology]
The cytoskeleton provides structural integrity to cells and serves as a key component in mechanotransduction. Tensins are thought to provide a force-bearing linkage between integrins and the actin cytoskeleton; yet, direct evidence of tensin’s role in mechanotransduction is lacking. We here report that local force application to epithelial cells using... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Joleen S. Cheah, Kyle A. Jacobs, Volkmar Heinrich, Su Hao Lo, Soichiro Yamada Tags: Brief Reports Biological Sciences Source Type: research

Mechanical fatigue of human red blood cells [Cell Biology]
Fatigue arising from cyclic straining is a key factor in the degradation of properties of engineered materials and structures. Fatigue can also induce damage and fracture in natural biomaterials, such as bone, and in synthetic biomaterials used in implant devices. However, the mechanisms by which mechanical fatigue leads to deterioration... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Yuhao Qiang, Jia Liu, Ming Dao, Subra Suresh, E. Du Tags: Physical Sciences Source Type: research

Atp6ap2 deletion causes extensive vacuolation that consumes the insulin content of pancreatic {beta} cells [Cell Biology]
Pancreatic β cells store insulin within secretory granules which undergo exocytosis upon elevation of blood glucose levels. Crinophagy and autophagy are instead responsible to deliver damaged or old granules to acidic lysosomes for intracellular degradation. However, excessive consumption of insulin granules can impair β cell function and cause diabetes. Atp6ap2... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Katrina J. Binger, Martin Neukam, Sudhir Gopal Tattikota, Fatimunnisa Qadri, Dmytro Puchkov, Diana M. Willmes, Sabrina Wurmsee, Sabrina Geisberger, Ralf Dechend, Klemens Raile, Thomas Kurth, Genevieve Nguyen, Matthew N. Poy, Michele Solimena, Dominik N. M Tags: Biological Sciences Source Type: research

Relative hydrophilicities of cis and trans formamides [Chemistry]
Secondary formamides are widely encountered in biology and exist as mixtures of both cis and trans isomers. Here, we assess hydrophilicity differences between isomeric formamides through direct competition experiments. Formamides bearing long aliphatic chains were sequestered in a water-soluble molecular container having a hydrophobic cavity with an end open to... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Yong-Sheng Li, Luis Escobar, Yu-Jie Zhu, Yoram Cohen, Pablo Ballester, Julius Rebek Jr., Yang Yu Tags: Physical Sciences Source Type: research

Heme binding to human CLOCK affects interactions with the E-box [Chemistry]
The circadian clock is an endogenous time-keeping system that is ubiquitous in animals and plants as well as some bacteria. In mammals, the clock regulates the sleep–wake cycle via 2 basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) domain proteins—CLOCK and BMAL1. There is emerging evidence to suggest that heme affects circadian control, through... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Samuel L. Freeman, Hanna Kwon, Nicola Portolano, Gary Parkin, Umakhanth Venkatraman Girija, Jaswir Basran, Alistair J. Fielding, Louise Fairall, Dimitri A. Svistunenko, Peter C. E. Moody, John W. R. Schwabe, Charalambos P. Kyriacou, Emma L. Raven Tags: Biological Sciences Source Type: research

Climate drives loss of phylogenetic diversity in a grassland community [Ecology]
While climate change has already profoundly influenced biodiversity through local extinctions, range shifts, and altered interactions, its effects on the evolutionary history contained within sets of coexisting species—or phylogenetic community diversity—have yet to be documented. Phylogenetic community diversity may be a proxy for the diversity of functional strategies that can... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Daijiang Li, Jesse E. D. Miller, Susan Harrison Tags: Biological Sciences Source Type: research

Fishing down then up the food web of an invaded lake [Ecology]
Analysis of commercial catches reveals a serial depletion of some oceanic fish stocks over time, resulting in fisheries focusing on increasingly smaller species closer to the base of the food chain. This effect, described as fishing down the marine food web, is observed when the trophic level of the catch... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Erin S. Dunlop, Daisuke Goto, Donald A. Jackson Tags: Biological Sciences Source Type: research

The value of thoughts and prayers [Economic Sciences]
In this study, we elicit the value of receiving thoughts and prayers... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Linda Thunstrom, Shiri Noy Tags: Brief Reports Social Sciences Source Type: research

Fine particulate matter damages and value added in the US economy [Economic Sciences]
Emissions of most pollutants that result in fine particulate matter (PM2.5) formation have been decreasing in the United States. However, this trend has not been uniform across all sectors or regions of the economy. We use integrated assessment models (IAMs) to compute marginal damages for PM2.5-related emissions for each county... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Peter Tschofen, Ines L. Azevedo, Nicholas Z. Muller Tags: Physical Sciences Source Type: research

Neuromuscular actuation of biohybrid motile bots [Engineering]
The integration of muscle cells with soft robotics in recent years has led to the development of biohybrid machines capable of untethered locomotion. A major frontier that currently remains unexplored is neuronal actuation and control of such muscle-powered biohybrid machines. As a step toward this goal, we present here a... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Onur Aydin, Xiaotian Zhang, Sittinon Nuethong, Gelson J. Pagan-Diaz, Rashid Bashir, Mattia Gazzola, M. Taher A. Saif Tags: Physical Sciences Source Type: research

Elevated mutation and selection in wild emmer wheat in response to 28 years of global warming [Evolution]
Global warming has been documented to threaten wild plants with strong selection pressures, but how plant populations respond genetically to the threats remains poorly understood. We characterized the genetic responses of 10 wild emmer wheat (Triticum dicoccoides Koern.; WEW) populations in Israel, sampling them in 1980 and again in 2008,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - October 1, 2019 Category: Science Authors: Yong-Bi Fu, Gregory W. Peterson, Carolee Horbach, David J. Konkin, Avigdor Beiles, Eviatar Nevo Tags: Biological Sciences Source Type: research