135,264 results match your criteria Proceedings of the National Academy of Sciences of the United States of America[Journal]


Musical pleasure and musical emotions.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Science and Technology of Music and Sound, UMR 9912, Institut de Recherche et Coordination Acoustique/Musique, CNRS, Sorbonne Université, 75004 Paris, France

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http://dx.doi.org/10.1073/pnas.1900369116DOI Listing
February 2019

E-protein regulatory network links TCR signaling to effector Treg cell differentiation.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Chinese Academy of Sciences (CAS) Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China;

T cell antigen receptor (TCR) signaling is essential for the differentiation and maintenance of effector regulatory T (Treg) cells. However, the contribution of individual TCR-dependent genes in Treg cells to the maintenance of immunotolerance remains largely unknown. Here we demonstrate that Treg cells lacking E protein undergo further differentiation into effector cells that exhibit high expression of effector Treg signature genes, including IRF4, ICOS, CD103, KLRG-1, and RORγt. Read More

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http://dx.doi.org/10.1073/pnas.1800494116DOI Listing
February 2019

Metalearners for estimating heterogeneous treatment effects using machine learning.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Statistics, University of California, Berkeley, CA 94720;

There is growing interest in estimating and analyzing heterogeneous treatment effects in experimental and observational studies. We describe a number of metaalgorithms that can take advantage of any supervised learning or regression method in machine learning and statistics to estimate the conditional average treatment effect (CATE) function. Metaalgorithms build on base algorithms-such as random forests (RFs), Bayesian additive regression trees (BARTs), or neural networks-to estimate the CATE, a function that the base algorithms are not designed to estimate directly. Read More

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http://dx.doi.org/10.1073/pnas.1804597116DOI Listing
February 2019

Pivotal role for α integrins in sustained Tfh support of the germinal center response for long-lived plasma cell generation.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642;

CD4+ follicular helper T cells (Tfh) are essential for germinal center (GC) reactions in the lymph node that generate high-affinity, long-lived plasma cells (LLPCs). Temporal GC analysis suggests B memory cells (Bmem) are generated early, while LLPCs are generated late in the GC reaction. Distinct roles for Tfh at these temporally different stages are not yet clear. Read More

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http://dx.doi.org/10.1073/pnas.1809329116DOI Listing
February 2019

Quantum experiments and graphs II: Quantum interference, computation, and state generation.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, 1090 Vienna, Austria;

We present an approach to describe state-of-the-art photonic quantum experiments using graph theory. There, the quantum states are given by the coherent superpositions of perfect matchings. The crucial observation is that introducing complex weights in graphs naturally leads to quantum interference. Read More

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http://dx.doi.org/10.1073/pnas.1815884116DOI Listing
February 2019

Altered neural odometry in the vertical dimension.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Experimental Psychology, University College London, London WC1H 0AP, United Kingdom

Entorhinal grid cells integrate sensory and self-motion inputs to provide a spatial metric of a characteristic scale. One function of this metric may be to help localize the firing fields of hippocampal place cells during formation and use of the hippocampal spatial representation ("cognitive map"). Of theoretical importance is the question of how this metric, and the resulting map, is configured in 3D space. Read More

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http://dx.doi.org/10.1073/pnas.1811867116DOI Listing
February 2019

Probing the link between residual entropy and viscosity of molecular fluids and model potentials.

Authors:
Ian H Bell

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Applied Chemicals and Materials Division, National Institute of Standards and Technology, Boulder, CO 80305

This work investigates the link between residual entropy and viscosity based on wide-ranging, highly accurate experimental and simulation data. This link was originally postulated by Rosenfeld in 1977 [Rosenfeld Y (1977) 15:2545-2549], and it is shown that this scaling results in an approximately monovariate relationship between residual entropy and reduced viscosity for a wide range of molecular fluids [argon, methane, [Formula: see text], [Formula: see text], refrigerant R-134a (1,1,1,2-tetrafluoroethane), refrigerant R-125 (pentafluoroethane), methanol, and water] and a range of model potentials (hard sphere, inverse power, Lennard-Jones, and Weeks-Chandler-Andersen). While the proposed "universal" correlation of Rosenfeld is shown to be far from universal, when used with the appropriate density scaling for molecular fluids, the viscosity of nonassociating molecular fluids can be mapped onto the model potentials. Read More

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http://dx.doi.org/10.1073/pnas.1815943116DOI Listing
February 2019

Nanometer-accuracy distance measurements between fluorophores at the single-molecule level.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158.

Light microscopy is a powerful tool for probing the conformations of molecular machines at the single-molecule level. Single-molecule Förster resonance energy transfer can measure intramolecular distance changes of single molecules in the range of 2 to 8 nm. However, current superresolution measurements become error-prone below 25 nm. Read More

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http://dx.doi.org/10.1073/pnas.1815826116DOI Listing
February 2019

TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich 80336, Germany;

Zn, Mg, and Ca are essential minerals required for a plethora of metabolic processes and signaling pathways. Different categories of cation-selective channels and transporters are therefore required to tightly control the cellular levels of individual metals in a cell-specific manner. However, the mechanisms responsible for the organismal balance of these essential minerals are poorly understood. Read More

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http://dx.doi.org/10.1073/pnas.1810633116DOI Listing
February 2019

Single-molecule excitation-emission spectroscopy.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Dynamical Spectroscopy, Department of Chemistry, Technical University of Munich, 85748 Garching, Germany;

Single-molecule spectroscopy (SMS) provides a detailed view of individual emitter properties and local environments without having to resort to ensemble averaging. While the last several decades have seen substantial refinement of SMS techniques, recording excitation spectra of single emitters still poses a significant challenge. Here we address this problem by demonstrating simultaneous collection of fluorescence emission and excitation spectra using a compact common-path interferometer and broadband excitation, which is implemented as an extension of a standard SMS microscope. Read More

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http://www.pnas.org/lookup/doi/10.1073/pnas.1808290116
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http://dx.doi.org/10.1073/pnas.1808290116DOI Listing
February 2019
7 Reads

Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030;

Genome damage and their defective repair have been etiologically linked to degenerating neurons in many subtypes of amyotrophic lateral sclerosis (ALS) patients; however, the specific mechanisms remain enigmatic. The majority of sporadic ALS patients feature abnormalities in the transactivation response DNA-binding protein of 43 kDa (TDP-43), whose nucleo-cytoplasmic mislocalization is characteristically observed in spinal motor neurons. While emerging evidence suggests involvement of other RNA/DNA binding proteins, like FUS in DNA damage response (DDR), the role of TDP-43 in DDR has not been investigated. Read More

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http://dx.doi.org/10.1073/pnas.1818415116DOI Listing
February 2019

Deep elastic strain engineering of bandgap through machine learning.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;

Nanoscale specimens of semiconductor materials as diverse as silicon and diamond are now known to be deformable to large elastic strains without inelastic relaxation. These discoveries harbinger a new age of deep elastic strain engineering of the band structure and device performance of electronic materials. Many possibilities remain to be investigated as to what pure silicon can do as the most versatile electronic material and what an ultrawide bandgap material such as diamond, with many appealing functional figures of merit, can offer after overcoming its present commercial immaturity. Read More

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http://dx.doi.org/10.1073/pnas.1818555116DOI Listing
February 2019

Emergence of analogy from relation learning.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Psychology, University of California, Los Angeles, CA 90095.

By middle childhood, humans are able to learn abstract semantic relations (e.g., antonym, synonym, category membership) and use them to reason by analogy. Read More

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http://dx.doi.org/10.1073/pnas.1814779116DOI Listing
February 2019

Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada;

The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of triple negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) are the most prominent component of the breast cancer microenvironment because they influence tumor progression and the response to therapies. Here we show that macrophages acquire an immunosuppressive phenotype and increase the expression of programmed death ligand-1 (PD-L1) when treated with reactive oxygen species (ROS) inducers such as the glutathione synthesis inhibitor, buthionine sulphoximine (BSO), and paclitaxel. Read More

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http://dx.doi.org/10.1073/pnas.1819473116DOI Listing
February 2019

Structural basis for activity of TRIC counter-ion channels in calcium release.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;

Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca from intracellular stores. TRIC activity is controlled by voltage and Ca modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca-bound and Ca-free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. Read More

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http://dx.doi.org/10.1073/pnas.1817271116DOI Listing
February 2019

Solution to the 50-year-old Okazaki-fragment problem.

Authors:
Peter M Burgers

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110

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http://dx.doi.org/10.1073/pnas.1900372116DOI Listing
February 2019

PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin.

Proc Natl Acad Sci U S A 2019 Feb 15. Epub 2019 Feb 15.

Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, Canada H2W 1R7;

Precise modulation of hepatic glucose metabolism is crucial during the fasting and feeding cycle and is controlled by the actions of circulating insulin and glucagon. The insulin-signaling pathway requires insulin receptor substrate 1 (IRS1) and IRS2, which are found to be dysregulated in diabetes and obesity. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) is a fasting-induced transcriptional coactivator. Read More

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http://dx.doi.org/10.1073/pnas.1815150116DOI Listing
February 2019

Extreme diversification of floral volatiles within and among species of (Saxifragaceae).

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA 95060.

A major challenge in evolutionary biology is to understand how complex traits of multiple functions have diversified and codiversified across interacting lineages and geographic ranges. We evaluate intra- and interspecific variation in floral scent, which is a complex trait of documented importance for mutualistic and antagonistic interactions between plants, pollinators, and herbivores. We performed a large-scale, phylogenetically structured study of an entire plant genus (, Saxifragaceae), of which several species are coevolving with specialized pollinating floral parasites of the moth genus (Prodoxidae). Read More

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http://dx.doi.org/10.1073/pnas.1809007116DOI Listing
February 2019

Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

School of Integrative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801

A fundamental question in evolutionary biology is how genetic novelty arises. De novo gene birth is a recently recognized mechanism, but the evolutionary process and function of putative de novo genes remain largely obscure. With a clear life-saving function, the diverse antifreeze proteins of polar fishes are exemplary adaptive innovations and models for investigating new gene evolution. Read More

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http://dx.doi.org/10.1073/pnas.1817138116DOI Listing
February 2019

Mobile platform for rapid sub-picogram-per-milliliter, multiplexed, digital droplet detection of proteins.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

School of Engineering and Applied Science, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321;

Digital droplet assays-in which biological samples are compartmentalized into millions of femtoliter-volume droplets and interrogated individually-have generated enormous enthusiasm for their ability to detect biomarkers with single-molecule sensitivity. These assays have untapped potential for point-of-care diagnostics but are currently mainly confined to laboratory settings, due to the instrumentation necessary to serially generate, control, and measure tens of millions of droplets/compartments. To address this challenge, we developed an optofluidic platform that miniaturizes digital assays into a mobile format by parallelizing their operation. Read More

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http://dx.doi.org/10.1073/pnas.1814110116DOI Listing
February 2019

Concentric organization of A- and B-type lamins predicts their distinct roles in the spatial organization and stability of the nuclear lamina.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261;

The nuclear lamina is an intermediate filament meshwork adjacent to the inner nuclear membrane (INM) that plays a critical role in maintaining nuclear shape and regulating gene expression through chromatin interactions. Studies have demonstrated that A- and B-type lamins, the filamentous proteins that make up the nuclear lamina, form independent but interacting networks. However, whether these lamin subtypes exhibit a distinct spatial organization or whether their organization has any functional consequences is unknown. Read More

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http://dx.doi.org/10.1073/pnas.1810070116DOI Listing
February 2019

Generalizing the effects of chirality on block copolymer assembly.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan;

We explore the generality of the influence of segment chirality on the self-assembled structure of achiral-chiral diblock copolymers. Poly(cyclohexylglycolide) (PCG)-based chiral block copolymers (BCPs*), poly(benzyl methacrylate)--poly(d-cyclohexylglycolide) (PBnMA-PDCG) and PBnMA--poly(l-cyclohexyl glycolide) (PBnMA-PLCG), were synthesized for purposes of systematic comparison with polylactide (PLA)-based BCPs*, previously shown to exhibit chirality transfer from monomeric unit to the multichain domain morphology. Opposite-handed PCG helical chains in the enantiomeric BCPs* were identified by the vibrational circular dichroism (VCD) studies revealing transfer from chiral monomers to chiral intrachain conformation. Read More

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http://dx.doi.org/10.1073/pnas.1812356116DOI Listing
February 2019

Three-dimensional optical trapping and orientation of microparticles for coherent X-ray diffraction imaging.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Chemical Sciences & Engineering Division, Argonne National Laboratory, Lemont, IL 60439;

Optical trapping has been implemented in many areas of physics and biology as a noncontact sample manipulation technique to study the structure and dynamics of nano- and mesoscale objects. It provides a unique approach for manipulating microscopic objects without inducing undesired changes in structure. Combining optical trapping with hard X-ray microscopy techniques, such as coherent diffraction imaging and crystallography, provides a nonperturbing environment where electronic and structural dynamics of an individual particle in solution can be followed in situ. Read More

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http://dx.doi.org/10.1073/pnas.1720785116DOI Listing
February 2019

WNK4 kinase is a physiological intracellular chloride sensor.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;

With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. Read More

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http://dx.doi.org/10.1073/pnas.1817220116DOI Listing
February 2019

Fate mapping reveals the age structure of the peripheral T cell compartment.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, NSW 2052, Australia;

Accumulating evidence indicates that the immune system does not develop in a linear fashion, but rather as distinct developmental layers formed from sequential waves of hematopoietic stem cells, each giving rise to unique populations of immune cells at different stages of development. Although recent studies have indicated that conventional CD8 T cells produced in early life persist into adulthood and exhibit distinct roles during infection, the developmental architecture of the peripheral T cell compartment remains undefined. In this study, we used a mouse model to permanently label CD8 T cells produced during distinct windows of development and traced their history to generate fate maps of CD8 T cells produced during different stages of life. Read More

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http://www.pnas.org/lookup/doi/10.1073/pnas.1811634116
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http://dx.doi.org/10.1073/pnas.1811634116DOI Listing
February 2019
2 Reads

Multiple interactive memory representations underlie the induction of false memory.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China;

Theoretical and computational models such as transfer-appropriate processing (TAP) and global matching models have emphasized the encoding-retrieval interaction of memory representations in generating false memories, but relevant neural mechanisms are still poorly understood. By manipulating the sensory modalities (visual and auditory) at different processing stages (learning and test) in the Deese-Roediger-McDermott task, we found that the auditory-learning visual-test (AV) group produced more false memories (59%) than the other three groups (42∼44%) [i.e. Read More

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http://dx.doi.org/10.1073/pnas.1817925116DOI Listing
February 2019

Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA 02215;

Previous studies have shown that insulin and IGF-1 signaling in the brain, especially the hypothalamus, is important for regulation of systemic metabolism. Here, we develop mice in which we have specifically inactivated both insulin receptors (IRs) and IGF-1 receptors (IGF1Rs) in the hippocampus (Hippo-DKO) or central amygdala (CeA-DKO) by stereotaxic delivery of AAV-Cre into IR/IGF1R mice. Consequently, both Hippo-DKO and CeA-DKO mice have decreased levels of the GluA1 subunit of glutamate AMPA receptor and display increased anxiety-like behavior, impaired cognition, and metabolic abnormalities, including glucose intolerance. Read More

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http://dx.doi.org/10.1073/pnas.1817391116DOI Listing
February 2019

Microscopic description of acid-base equilibrium.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Chemistry and Applied Biosciences, Eidgenössische Technische Hochschule (ETH) Zürich, CH-6900 Lugano, Ticino, Switzerland;

Acid-base reactions are ubiquitous in nature. Understanding their mechanisms is crucial in many fields, from biochemistry to industrial catalysis. Unfortunately, experiments give only limited information without much insight into the molecular behavior. Read More

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http://dx.doi.org/10.1073/pnas.1819771116DOI Listing
February 2019

Six6 and Six7 coordinately regulate expression of middle-wavelength opsins in zebrafish.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Biological Sciences, School of Science, The University of Tokyo, 113-0033 Tokyo, Japan;

Color discrimination in the vertebrate retina is mediated by a combination of spectrally distinct cone photoreceptors, each expressing one of multiple cone opsins. The opsin genes diverged early in vertebrate evolution into four classes maximally sensitive to varying wavelengths of light: UV (SWS1), blue (SWS2), green (RH2), and red (LWS) opsins. Although the tetrachromatic cone system is retained in most nonmammalian vertebrate lineages, the transcriptional mechanism underlying gene expression of the cone opsins remains elusive, particularly for SWS2 and RH2 opsins, both of which have been lost in the mammalian lineage. Read More

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http://dx.doi.org/10.1073/pnas.1812884116DOI Listing
February 2019

Five computational developability guidelines for therapeutic antibody profiling.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom;

Therapeutic mAbs must not only bind to their target but must also be free from "developability issues" such as poor stability or high levels of aggregation. While small-molecule drug discovery benefits from Lipinski's rule of five to guide the selection of molecules with appropriate biophysical properties, there is currently no in silico analog for antibody design. Here, we model the variable domain structures of a large set of post-phase-I clinical-stage antibody therapeutics (CSTs) and calculate in silico metrics to estimate their typical properties. Read More

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http://dx.doi.org/10.1073/pnas.1810576116DOI Listing
February 2019

Unraveling materials Berry curvature and Chern numbers from real-time evolution of Bloch states.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Theory Department, Max Planck Institute for the Structure and Dynamics of Matter, Center for Free Electron Laser Science, 22761 Hamburg, Germany;

Materials can be classified by the topological character of their electronic structure and, in this perspective, global attributes immune to local deformations have been discussed in terms of Berry curvature and Chern numbers. Except for instructional simple models, linear response theories have been ubiquitously used in calculations of topological properties of real materials. Here we propose a completely different and versatile approach to obtain the topological characteristics of materials by calculating physical observables from the real-time evolving Bloch states: The cell-averaged current density reveals the anomalous velocities that lead to the conductivity quantum. Read More

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http://dx.doi.org/10.1073/pnas.1816904116DOI Listing
February 2019

Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada;

Activity-dependent translation requires the transport of mRNAs within membraneless protein assemblies known as neuronal granules from the cell body toward synaptic regions. Translation of mRNA is inhibited in these granules during transport but quickly activated in response to neuronal stimuli at the synapse. This raises an important question: how does synaptic activity trigger translation of once-silenced mRNAs? Here, we demonstrate a strong connection between phase separation, the process underlying the formation of many different types of cellular granules, and in vitro inhibition of translation. Read More

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http://dx.doi.org/10.1073/pnas.1814385116DOI Listing
February 2019

Opposite regulation of Wnt/β-catenin and Shh signaling pathways by Rack1 controls mammalian cerebellar development.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Neurobiology, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China;

The development of the cerebellum depends on intricate processes of neurogenesis, migration, and differentiation of neural stem cells (NSCs) and progenitor cells. Defective cerebellar development often results in motor dysfunctions and psychiatric disorders. Understanding the molecular mechanisms that underlie the complex development of the cerebellum will facilitate the development of novel treatment options. Read More

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http://dx.doi.org/10.1073/pnas.1813244116DOI Listing
February 2019

Mitochondrial small heat shock protein mediates seed germination via thermal sensing.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Zhejiang University, 310029 Zhejiang, China;

Seed germination is an energy demanding process that requires functional mitochondria upon imbibition. However, how mitochondria fine tune seed germination, especially in response to the dynamics of environmental temperature, remains largely unknown at the molecular level. Here, we report a mitochondrial matrix-localized heat shock protein GhHSP24. Read More

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http://dx.doi.org/10.1073/pnas.1815790116DOI Listing
February 2019

Evolution of resilience in protein interactomes across the tree of life.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Computer Science, Stanford University, Stanford, CA 94305;

Phenotype robustness to environmental fluctuations is a common biological phenomenon. Although most phenotypes involve multiple proteins that interact with each other, the basic principles of how such interactome networks respond to environmental unpredictability and change during evolution are largely unknown. Here we study interactomes of 1,840 species across the tree of life involving a total of 8,762,166 protein-protein interactions. Read More

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http://dx.doi.org/10.1073/pnas.1818013116DOI Listing
February 2019

Self-assembled ruthenium (II) metallacycles and metallacages with imidazole-based ligands and their in vitro anticancer activity.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Department of Chemistry, University of Utah, Salt Lake City, UT 84112;

Six tetranuclear rectangular metallacycles were synthesized via the [2+2] coordination-driven self-assembly of imidazole-based ditopic donor 1,4-bis(imidazole-1-yl)benzene and 1,3-bis(imidazol-1-yl)benzene, with dinuclear half-sandwich -cymene ruthenium(II) acceptors [Ru(µ-η-oxalato)(η--cymene)](SOCF), [Ru(µ-η-2,5-dioxido-1,4-benzoquinonato)(η--cymene)](SOCF) and [Ru(µ-η-5,8-dioxido-1,4-naphtoquinonato)(η--cymene)](SOCF), respectively. Likewise, three hexanuclear trigonal prismatic metallacages were prepared via the [2+3] self-assembly of tritopic donor of 1,3,5-tri(1-imidazol-1-yl)benzene with these ruthenium(II) acceptors respectively. Self-selection of the single symmetrical and stable metallacycle and cage was observed although there is the possibility of forming different conformational isomeric products due to different binding modes of these imidazole-based donors. Read More

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http://dx.doi.org/10.1073/pnas.1818677116DOI Listing
February 2019

Local frustration around enzyme active sites.

Proc Natl Acad Sci U S A 2019 Feb 14. Epub 2019 Feb 14.

Protein Physiology Laboratory, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas-Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, C1428EGA Buenos Aires, Argentina;

Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. Read More

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http://dx.doi.org/10.1073/pnas.1819859116DOI Listing
February 2019

Anaphase-promoting complex/cyclosome regulates RdDM activity by degrading DMS3 in .

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, 200438 Shanghai, China;

During RNA-directed DNA methylation (RdDM), the DDR complex, composed of DRD1, DMS3, and RDM1, is responsible for recruiting DNA polymerase V (Pol V) to silence transposable elements (TEs) in plants. However, how the DDR complex is regulated remains unexplored. Here, we show that the anaphase-promoting complex/cyclosome (APC/C) regulates the assembly of the DDR complex by targeting DMS3 for degradation. Read More

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http://dx.doi.org/10.1073/pnas.1816652116DOI Listing
February 2019
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Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455;

Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSCs) allows the generation of myogenic progenitors endowed with enhanced regenerative capacity. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages. Read More

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http://dx.doi.org/10.1073/pnas.1808303116DOI Listing
February 2019

Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Geriatric Research Educational and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240;

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a unique brain-specific deubiquitinating enzyme. Mutations in and aberrant function of UCHL1 have been linked to many neurological disorders. UCHL1 activity protects neurons from hypoxic injury, and binding of stroke-induced reactive lipid species to the cysteine 152 (C152) of UCHL1 unfolds the protein and disrupts its function. Read More

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http://dx.doi.org/10.1073/pnas.1821282116DOI Listing
February 2019

H5N8 and H7N9 packaging signals constrain HA reassortment with a seasonal H3N2 influenza A virus.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322

Influenza A virus (IAV) has a segmented genome, which () allows for exchange of gene segments in coinfected cells, termed reassortment, and () necessitates a selective packaging mechanism to ensure incorporation of a complete set of segments into virus particles. Packaging signals serve as segment identifiers and enable segment-specific packaging. We have previously shown that packaging signals limit reassortment between heterologous IAV strains in a segment-dependent manner. Read More

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http://dx.doi.org/10.1073/pnas.1818494116DOI Listing
February 2019

Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103;

We used cryo-electron microscopy (cryo-EM) to reconstruct actin filaments with bound AMPPNP (β,γ-imidoadenosine 5'-triphosphate, an ATP analog, resolution 3.1 Å), ADP-P (ADP with inorganic phosphate, resolution 3.1 Å), or ADP (resolution 3. Read More

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http://dx.doi.org/10.1073/pnas.1807028115DOI Listing
February 2019

Biosynthesis of magnetic nanoparticles from nano-degradation products revealed in human stem cells.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Laboratoire Matière et Systèmes Complexes, UMR 7057, CNRS and University Paris Diderot, 75205 Paris Cedex 13, France;

While magnetic nanoparticles offer exciting possibilities for stem cell imaging or tissue bioengineering, their long-term intracellular fate remains to be fully documented. Besides, it appears that magnetic nanoparticles can occur naturally in human cells, but their origin and potentially endogenous synthesis still need further understanding. In an effort to explore the life cycle of magnetic nanoparticles, we investigated their transformations upon internalization in mesenchymal stem cells and as a function of the cells' differentiation status (undifferentiated, or undergoing adipogenesis, osteogenesis, and chondrogenesis). Read More

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http://dx.doi.org/10.1073/pnas.1816792116DOI Listing
February 2019

Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125

There is great interest in being able to spread beneficial traits throughout wild populations in ways that are self-sustaining. Here, we describe a chromosomal selfish genetic element, [Cleave and Rescue ()], able to achieve this goal. comprises two linked chromosomal components. Read More

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http://dx.doi.org/10.1073/pnas.1816928116DOI Listing
February 2019

Atomic-level characterization of protein-protein association.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

D. E. Shaw Research, New York, NY 10036;

Despite the biological importance of protein-protein complexes, determining their structures and association mechanisms remains an outstanding challenge. Here, we report the results of atomic-level simulations in which we observed five protein-protein pairs repeatedly associate to, and dissociate from, their experimentally determined native complexes using a molecular dynamics (MD)-based sampling approach that does not make use of any prior structural information about the complexes. To study association mechanisms, we performed additional, conventional MD simulations, in which we observed numerous spontaneous association events. Read More

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http://dx.doi.org/10.1073/pnas.1815431116DOI Listing
February 2019

Dimers of mitochondrial ATP synthase induce membrane curvature and self-assemble into rows.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Department of Structural Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany

Mitochondrial ATP synthases form dimers, which assemble into long ribbons at the rims of the inner membrane cristae. We reconstituted detergent-purified mitochondrial ATP synthase dimers from the green algae sp. and the yeast into liposomes and examined them by electron cryotomography. Read More

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http://dx.doi.org/10.1073/pnas.1816556116DOI Listing
February 2019

Coupling between dynamic 3D tissue architecture and BMP morphogen signaling during wing morphogenesis.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland;

At the level of organ formation, tissue morphogenesis drives developmental processes in animals, often involving the rearrangement of two-dimensional (2D) structures into more complex three-dimensional (3D) tissues. These processes can be directed by growth factor signaling pathways. However, little is known about how such morphological changes affect the spatiotemporal distribution of growth factor signaling. Read More

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http://dx.doi.org/10.1073/pnas.1815427116DOI Listing
February 2019

Defining the economic scope for ecosystem-based fishery management.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Resources for the Future, Washington, DC 20036.

The emergence of ecosystem-based fisheries management (EBFM) has broadened the policy scope of fisheries management by accounting for the biological and ecological connectivity of fisheries. Less attention, however, has been given to the economic connectivity of fisheries. If fishers consider multiple fisheries when deciding where, when, and how much to fish, then management changes in one fishery can generate spillover impacts in other fisheries. Read More

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http://dx.doi.org/10.1073/pnas.1816545116DOI Listing
February 2019

Functional diversity of motoneurons in the oculomotor system.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain;

Extraocular muscles contain two types of muscle fibers according to their innervation pattern: singly innervated muscle fibers (SIFs), similar to most skeletal muscle fibers, and multiply innervated muscle fibers (MIFs). Morphological studies have revealed that SIF and MIF motoneurons are segregated anatomically and receive different proportions of certain afferents, suggesting that while SIF motoneurons would participate in the whole repertoire of eye movements, MIF motoneurons would contribute only to slow eye movements and fixations. We have tested that proposal by performing single-unit recordings, in alert behaving cats, of electrophysiologically identified MIF and SIF motoneurons in the abducens nucleus. Read More

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http://dx.doi.org/10.1073/pnas.1818524116DOI Listing
February 2019

FeoB contains a dual nucleotide-specific NTPase domain essential for ferrous iron uptake.

Proc Natl Acad Sci U S A 2019 Feb 13. Epub 2019 Feb 13.

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712

The Feo ferrous iron transporter is widely distributed among bacteria and archaea, but its mechanism of transport has not been fully elucidated. In , the transport system requires three proteins: the small cytosolic proteins FeoA and FeoC and a large cytoplasmic-membrane-associated protein FeoB, which has an N-terminal G-protein domain. We show that, in contrast to FeoB, which is solely a GTPase, the and FeoB proteins have both GTPase and ATPase activity. Read More

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http://dx.doi.org/10.1073/pnas.1817964116DOI Listing
February 2019