
显示样式: 排序: IF: - GO 导出
-
News Feature: A sea in the Amazon [Ecology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Amy McDermott
A tropical shrub called Chrysobalanus icaco pushes up through Brazil’s white sandy beaches. The plant’s leathery oval leaves and tough silver bark give it the distinct appearance of a mangrove species, adapted to a life buffeted by saltwater. Strangely, though, C. icaco also turns up more than a thousand miles inland, in the forests of the western Amazon. “We find fossil mangroves and associated coastal
-
Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Karim Mrouj; Nuria Andrés-Sánchez; Geronimo Dubra; Priyanka Singh; Michal Sobecki; Dhanvantri Chahar; Emile Al Ghoul; Ana Bella Aznar; Susana Prieto; Nelly Pirot; Florence Bernex; Benoit Bordignon; Cedric Hassen-Khodja; Martin Villalba; Liliana Krasinska; Daniel Fisher
Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global
-
Predicting transcriptional responses to cold stress across plant species [Plant Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Xiaoxi Meng; Zhikai Liang; Xiuru Dai; Yang Zhang; Samira Mahboub; Daniel W. Ngu; Rebecca L. Roston; James C. Schnable
Although genome-sequence assemblies are available for a growing number of plant species, gene-expression responses to stimuli have been cataloged for only a subset of these species. Many genes show altered transcription patterns in response to abiotic stresses. However, orthologous genes in related species often exhibit different responses to a given stress. Accordingly, data on the regulation of gene
-
An in vivo method for diversifying the functions of therapeutic antibodies [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ming Tian; Hwei-Ling Cheng; Michael T. Kimble; Kelly McGovern; Peyton Waddicor; Yiwei Chen; Elizabeth Cantor; Mengting Qiu; Marie-Elen Tuchel; Mai Dao; Frederick W. Alt
V(D)J recombination generates mature B cells that express huge repertoires of primary antibodies as diverse immunoglobulin (Ig) heavy chain (IgH) and light chain (IgL) of their B cell antigen receptors (BCRs). Cognate antigen binding to BCR variable region domains activates B cells into the germinal center (GC) reaction in which somatic hypermutation (SHM) modifies primary variable region-encoding
-
Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone [Statistics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Laura J. Whitworth; Rajan Troll; Antonio J. Pagán; Francisco J. Roca; Paul H. Edelstein; Mark Troll; David M. Tobin; Nguyen Hoan Phu; Nguyen Duc Bang; Guy E. Thwaites; Nguyen Thuy Thuong Thuong; Roger F. Sewell; Lalita Ramakrishnan
Adjunctive treatment with antiinflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates with a C/T variant in Leukotriene A4 Hydrolase (LTA4H), which regulates expression of the proinflammatory mediator leukotriene B4 (LTB4). TT homozygotes, with increased expression of LTA4H, have the highest survival when treated with dexamethasone
-
The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jihan Kim; Yuansheng Cao; Christopher Eddy; Youyuan Deng; Herbert Levine; Wouter-Jan Rappel; Bo Sun
Contact guidance is a major physical cue that modulates cancer cell morphology and motility, and is directly linked to the prognosis of cancer patients. Under physiological conditions, particularly in the three-dimensional (3D) extracellular matrix (ECM), the disordered assembly of fibers presents a complex directional bias to the cells. It is unclear how cancer cells respond to these noncoherent contact
-
Non-line-of-sight imaging over 1.43 km [Physics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Cheng Wu; Jianjiang Liu; Xin Huang; Zheng-Ping Li; Chao Yu; Jun-Tian Ye; Jun Zhang; Qiang Zhang; Xiankang Dou; Vivek K. Goyal; Feihu Xu; Jian-Wei Pan
Non–line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects from indirect light paths that scatter multiple times in the surrounding environment, which is of considerable interest in a wide range of applications. Whereas conventional imaging involves direct line-of-sight light transport to recover the visible objects, NLOS imaging aims to reconstruct the hidden objects from the indirect
-
Integration and transfer learning of single-cell transcriptomes via cFIT [Statistics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Minshi Peng; Yue Li; Brie Wamsley; Yuting Wei; Kathryn Roeder
Large, comprehensive collections of single-cell RNA sequencing (scRNA-seq) datasets have been generated that allow for the full transcriptional characterization of cell types across a wide variety of biological and clinical conditions. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these datasets or transfer knowledge from one to the other to
-
Theory of bulk photovoltaic effect in Anderson insulator [Applied Physical Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Hiroaki Ishizuka; Naoto Nagaosa
The localization of wavefunction by disorder makes a conductive material an insulator with vanishing conductivity at zero temperature. A similar outcome is expected for the photocurrent in semiconductor p-n junctions because the photoexcited carriers cannot drift through the device. In contrast, we here show numerically that the bulk photovoltaic effect—the photovoltaic effect in noncentrosymmetric
-
Aggression heuristics underlie animal dominance hierarchies and provide evidence of group-level social information [Psychological and Cognitive Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Elizabeth A. Hobson; Dan Mønster; Simon DeDeo
Members of a social species need to make appropriate decisions about who, how, and when to interact with others in their group. However, it has been difficult for researchers to detect the inputs to these decisions and, in particular, how much information individuals actually have about their social context. We present a method that can serve as a social assay to quantify how patterns of aggression
-
Structural insights into membrane remodeling by SNX1 [Biophysics and Computational Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Yan Zhang; Xiaoyun Pang; Jian Li; Jiashu Xu; Victor W. Hsu; Fei Sun
The sorting nexin (SNX) family of proteins deform the membrane to generate transport carriers in endosomal pathways. Here, we elucidate how a prototypic member, SNX1, acts in this process. Performing cryoelectron microscopy, we find that SNX1 assembles into a protein lattice that consists of helical rows of SNX1 dimers wrapped around tubular membranes in a crosslinked fashion. We also visualize the
-
Cas9-expressing chickens and pigs as resources for genome editing in livestock [Agricultural Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Beate Rieblinger; Hicham Sid; Denise Duda; Tarik Bozoglu; Romina Klinger; Antonina Schlickenrieder; Kamila Lengyel; Krzysztof Flisikowski; Tatiana Flisikowska; Nina Simm; Alessandro Grodziecki; Carolin Perleberg; Andrea Bähr; Lucie Carrier; Mayuko Kurome; Valeri Zakhartchenko; Barbara Kessler; Eckhard Wolf; Lutz Kettler; Harald Luksch; Ibrahim T. Hagag; Daniel Wise; Jim Kaufman; Benedikt B. Kaufer;
Genetically modified animals continue to provide important insights into the molecular basis of health and disease. Research has focused mostly on genetically modified mice, although other species like pigs resemble the human physiology more closely. In addition, cross-species comparisons with phylogenetically distant species such as chickens provide powerful insights into fundamental biological and
-
Emergent robustness of bacterial quorum sensing in fluid flow [Systems Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Mohit P. Dalwadi; Philip Pearce
Bacteria use intercellular signaling, or quorum sensing (QS), to share information and respond collectively to aspects of their surroundings. The autoinducers that carry this information are exposed to the external environment; consequently, they are affected by factors such as removal through fluid flow, a ubiquitous feature of bacterial habitats ranging from the gut and lungs to lakes and oceans
-
The imprinted lncRNA Peg13 regulates sexual preference and the sex-specific brain transcriptome in mice [Genetics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Maryam Keshavarz; Diethard Tautz
Mammalian genomes include many maternally and paternally imprinted genes. Most of these are also expressed in the brain, and several have been implicated in regulating specific behavioral traits. Here, we have used a knockout approach to study the function of Peg13, a gene that codes for a fast-evolving lncRNA (long noncoding RNA) and is part of a complex of imprinted genes on chromosome 15 in mice
-
{Gamma} valley transition metal dichalcogenide moire bands [Physics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Mattia Angeli; Allan H. MacDonald
The valence band maxima of most group VI transition metal dichalcogenide thin films remain at the Γ point all of the way from bulk to bilayer. In this paper, we develop a continuum theory of the moiré minibands that are formed in the valence bands of Γ-valley homobilayers by a small relative twist. Our effective theory is benchmarked against large-scale ab initio electronic structure calculations that
-
Discordant clinical features of identical hypertrophic cardiomyopathy twins [Genetics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Giuliana G. Repetti; Yuri Kim; Alexandre C. Pereira; Jodie Ingles; Mark W. Russell; Neal K. Lakdawala; Carolyn Y. Ho; Sharlene Day; Christopher Semsarian; Barbara McDonough; Steven R. DePalma; Daniel Quiat; Eric M. Green; Christine E. Seidman; J. G. Seidman
Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects ∼1 in 500 individuals and is characterized by increased left ventricular wall thickness. While HCM is caused by pathogenic variants in any one of eight sarcomere protein genes, clinical expression varies considerably, even among patients with the same pathogenic variant. To determine whether background genetic variation or
-
Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q [Biochemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ke Shi; Nicholas H. Moeller; Surajit Banerjee; Jennifer L. McCann; Michael A. Carpenter; Lulu Yin; Ramkumar Moorthy; Kayo Orellana; Daniel A. Harki; Reuben S. Harris; Hideki Aihara
Spontaneous deamination of DNA cytosine and adenine into uracil and hypoxanthine, respectively, causes C to T and A to G transition mutations if left unrepaired. Endonuclease Q (EndoQ) initiates the repair of these premutagenic DNA lesions in prokaryotes by cleaving the phosphodiester backbone 5′ of either uracil or hypoxanthine bases or an apurinic/apyrimidinic (AP) lesion generated by the excision
-
Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics [Developmental Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jason Ioannidis; Gunes Taylor; Debiao Zhao; Long Liu; Alewo Idoko-Akoh; Daoqing Gong; Robin Lovell-Badge; Silvana Guioli; Mike J. McGrew; Michael Clinton
In birds, males are the homogametic sex (ZZ) and females the heterogametic sex (ZW). Primary sex determination is thought to depend on a sex chromosome gene dosage mechanism, and the most likely sex determinant is the Z chromosome gene Doublesex and Mab-3–Related Transcription factor 1 (DMRT1). To clarify this issue, we used a CRISPR-Cas9–based monoallelic targeting approach and sterile surrogate hosts
-
Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Kristine Farmen; Sara K. Nissen; Morten G. Stokholm; Alex Iranzo; Karen Østergaard; Mónica Serradell; Marit Otto; Kristina B. Svendsen; Alicia Garrido; Dolores Vilas; Per Borghammer; Joan Santamaria; Arne Møller; Carles Gaig; David J. Brooks; Eduardo Tolosa; Nicola Pavese; Marina Romero-Ramos
Synucleinopathies are neurodegenerative diseases with both central and peripheral immune responses. However, whether the peripheral immune changes occur early in disease and their relation to brain events is yet unclear. Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) can precede synucleinopathy-related parkinsonism and provides a prodromal phenotype to study early Parkinson's disease
-
Shape changes and cooperativity in the folding of the central domain of the 16S ribosomal RNA [Chemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Naoto Hori; Natalia A. Denesyuk; D. Thirumalai
Both the small and large subunits of the ribosome, the molecular machine that synthesizes proteins, are complexes of ribosomal RNAs (rRNAs) and a number of proteins. In bacteria, the small subunit has a single 16S rRNA whose folding is the first step in its assembly. The central domain of the 16S rRNA folds independently, driven either by Mg2+ ions or by interaction with ribosomal proteins. To provide
-
Cadherin cis and trans interactions are mutually cooperative [Biophysics and Computational Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Connor J. Thompson; Vinh H. Vu; Deborah E. Leckband; Daniel K. Schwartz
Cadherin transmembrane proteins are responsible for intercellular adhesion in all biological tissues and modulate tissue morphogenesis, cell motility, force transduction, and macromolecular transport. The protein-mediated adhesions consist of adhesive trans interactions and lateral cis interactions. Although theory suggests cooperativity between cis and trans bonds, direct experimental evidence of
-
Drosophila clock cells use multiple mechanisms to transmit time-of-day signals in the brain [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Annika F. Barber; Shi Yi Fong; Anna Kolesnik; Michael Fetchko; Amita Sehgal
Regulation of circadian behavior and physiology by the Drosophila brain clock requires communication from central clock neurons to downstream output regions, but the mechanism by which clock cells regulate downstream targets is not known. We show here that the pars intercerebralis (PI), previously identified as a target of the morning cells in the clock network, also receives input from evening cells
-
Dynamics of hydraulic and contractile wave-mediated fluid transport during Drosophila oogenesis [Developmental Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jasmin Imran Alsous; Nicolas Romeo; Jonathan A. Jackson; Frank M. Mason; Jörn Dunkel; Adam C. Martin
From insects to mice, oocytes develop within cysts alongside nurse-like sister germ cells. Prior to fertilization, the nurse cells’ cytoplasmic contents are transported into the oocyte, which grows as its sister cells regress and die. Although critical for fertility, the biological and physical mechanisms underlying this transport process are poorly understood. Here, we combined live imaging of germline
-
Architecturally complex O-glycopeptidases are customized for mucin recognition and hydrolysis [Biochemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Benjamin Pluvinage; Elizabeth Ficko-Blean; Ilit Noach; Christopher Stuart; Nicole Thompson; Hayden McClure; Nakita Buenbrazo; Warren Wakarchuk; Alisdair B. Boraston
A challenge faced by peptidases is the recognition of highly diverse substrates. A feature of some peptidase families is the capacity to specifically use post-translationally added glycans present on their protein substrates as a recognition determinant. This is ultimately critical to enabling peptide bond hydrolysis. This class of enzyme is also frequently large and architecturally sophisticated.
-
Phytophthora sojae effector Avr1d functions as an E2 competitor and inhibits ubiquitination activity of GmPUB13 to facilitate infection [Microbiology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Yachun Lin; Qinli Hu; Jia Zhou; Weixiao Yin; Deqiang Yao; Yuanyuan Shao; Yao Zhao; Baodian Guo; Yeqiang Xia; Qian Chen; Yan Wang; Wenwu Ye; Qi Xie; Brett M. Tyler; Weiman Xing; Yuanchao Wang
Oomycete pathogens such as Phytophthora secrete a repertoire of effectors into host cells to manipulate host immunity and benefit infection. In this study, we found that an RxLR effector, Avr1d, promoted Phytophthora sojae infection in soybean hairy roots. Using a yeast two-hybrid screen, we identified the soybean E3 ubiquitin ligase GmPUB13 as a host target for Avr1d. By coimmunoprecipitation (Co-IP)
-
Emergence of dynamic vortex glasses in disordered polar active fluids [Physics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Amélie Chardac; Suraj Shankar; M. Cristina Marchetti; Denis Bartolo
In equilibrium, disorder conspires with topological defects to redefine the ordered states of matter in systems as diverse as crystals, superconductors, and liquid crystals. Far from equilibrium, however, the consequences of quenched disorder on active condensed matter remain virtually uncharted. Here, we reveal a state of strongly disordered active matter with no counterparts in equilibrium: a dynamical
-
Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Shoib S. Siddiqui; Chirag Dhar; Venkatasubramaniam Sundaramurthy; Aniruddha Sasmal; Hai Yu; Esther Bandala-Sanchez; Miaomiao Li; Xiaoxiao Zhang; Xi Chen; Leonard C. Harrison; Ding Xu; Ajit Varki
Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did
-
Anomalous nanoparticle surface diffusion in LCTEM is revealed by deep learning-assisted analysis [Chemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Vida Jamali; Cory Hargus; Assaf Ben-Moshe; Amirali Aghazadeh; Hyun Dong Ha; Kranthi K. Mandadapu; A. Paul Alivisatos
The motion of nanoparticles near surfaces is of fundamental importance in physics, biology, and chemistry. Liquid cell transmission electron microscopy (LCTEM) is a promising technique for studying motion of nanoparticles with high spatial resolution. Yet, the lack of understanding of how the electron beam of the microscope affects the particle motion has held back advancement in using LCTEM for in
-
Chloride-dependent conformational changes in the GlyT1 glycine transporter [Biochemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Yuan-Wei Zhang; Stacy Uchendu; Vanessa Leone; Richard T. Bradshaw; Ntumba Sangwa; Lucy R. Forrest; Gary Rudnick
The human GlyT1 glycine transporter requires chloride for its function. However, the mechanism by which Cl− exerts its influence is unknown. To examine the role that Cl− plays in the transport cycle, we measured the effect of Cl− on both glycine binding and conformational changes. The ability of glycine to displace the high-affinity radioligand [3H]CHIBA-3007 required Na+ and was potentiated over 1
-
A narrow ear canal reduces sound velocity to create additional acoustic inputs in a microscale insect ear [Biophysics and Computational Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Daniel Veitch; Emine Celiker; Sarah Aldridge; Christian Pulver; Carl D. Soulsbury; Thorin Jonsson; Charlie Woodrow; Fernando Montealegre-Z
Located in the forelegs, katydid ears are unique among arthropods in having outer, middle, and inner components, analogous to the mammalian ear. Unlike mammals, sound is received externally via two tympanic membranes in each ear and internally via a narrow ear canal (EC) derived from the respiratory tracheal system. Inside the EC, sound travels slower than in free air, causing temporal and pressure
-
Excitatory cholecystokinin neurons of the midbrain integrate diverse temporal responses and drive auditory thalamic subdomains [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Lauren J. Kreeger; Catherine J. Connelly; Preeti Mehta; Boris V. Zemelman; Nace L. Golding
The central nucleus of the inferior colliculus (ICC) integrates information about different features of sound and then distributes this information to thalamocortical circuits. However, the lack of clear definitions of circuit elements in the ICC has limited our understanding of the nature of these circuit transformations. Here, we combine virus-based genetic access with electrophysiological and optogenetic
-
Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2 [Microbiology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-23 Yinghui Liu; Gaowei Hu; Yuyan Wang; Wenlin Ren; Xiaomin Zhao; Fansen Ji; Yunkai Zhu; Fei Feng; Mingli Gong; Xiaohui Ju; Yuanfei Zhu; Xia Cai; Jun Lan; Jianying Guo; Min Xie; Lin Dong; Zihui Zhu; Jie Na; Jianping Wu; Xun Lan; Youhua Xie; Xinquan Wang; Zhenghong Yuan; Rong Zhang; Qiang Ding
The pandemic of COVID-19, caused by SARS-CoV-2, is a major global health threat. Epidemiological studies suggest that bats (Rhinolophus affinis) are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of
-
Impacts of introducing and lifting nonpharmaceutical interventions on COVID-19 daily growth rate and compliance in the United States Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-23 Surya Singh; Mujaheed Shaikh; Katharina Hauck; Marisa Miraldo
We evaluate the impacts of implementing and lifting nonpharmaceutical interventions (NPIs) in US counties on the daily growth rate of COVID-19 cases and compliance, measured through the percentage of devices staying home, and evaluate whether introducing and lifting NPIs protecting selective populations is an effective strategy. We use difference-in-differences methods, leveraging on daily county-level
-
Local induction of bladder Th1 responses to combat urinary tract infections [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jianxuan Wu; Chunjing Bao; R. Lee Reinhardt; Soman N. Abraham
Given the high frequency of urinary tract infections (UTIs) and their recurrence, there is keen interest in developing effective UTI vaccines. Currently, most vaccine studies, including those in humans, involve parenteral vaccination aimed at evoking and sustaining elevated levels of systemic antibody directed at the uropathogens. In view of recent reports of aberrant Th2-biased bladder immune responses
-
Designing self-assembling kinetics with differentiable statistical physics models [Physics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Carl P. Goodrich; Ella M. King; Samuel S. Schoenholz; Ekin D. Cubuk; Michael P. Brenner
The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely
-
Transcriptional heterogeneity and tightly regulated changes in gene expression during Plasmodium berghei sporozoite development [Microbiology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Haikel N. Bogale; Tales V. Pascini; Sachie Kanatani; Juliana M. Sá; Thomas E. Wellems; Photini Sinnis; Joel Vega-Rodríguez; David Serre
Despite the critical role of Plasmodium sporozoites in malaria transmission, we still know little about the mechanisms underlying their development in mosquitoes. Here, we use single-cell RNA sequencing to characterize the gene expression profiles of 16,038 Plasmodium berghei sporozoites isolated throughout their development from midgut oocysts to salivary glands, and from forced salivation experiments
-
High-sensitivity heat-capacity measurements on Sr2RuO4 under uniaxial pressure [Physics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 You-Sheng Li; Naoki Kikugawa; Dmitry A. Sokolov; Fabian Jerzembeck; Alexandra S. Gibbs; Yoshiteru Maeno; Clifford W. Hicks; Jörg Schmalian; Michael Nicklas; Andrew P. Mackenzie
A key question regarding the unconventional superconductivity of Sr2RuO4 remains whether the order parameter is single- or two-component. Under a hypothesis of two-component superconductivity, uniaxial pressure is expected to lift their degeneracy, resulting in a split transition. The most direct and fundamental probe of a split transition is heat capacity. Here, we report measurement of heat capacity
-
Ligand effects on phase separation of multivalent macromolecules [Biophysics and Computational Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Kiersten M. Ruff; Furqan Dar; Rohit V. Pappu
Biomolecular condensates enable spatial and temporal control over cellular processes by concentrating biomolecules into nonstoichiometric assemblies. Many condensates form via reversible phase transitions of condensate-specific multivalent macromolecules known as scaffolds. Phase transitions of scaffolds can be regulated by changing the concentrations of ligands, which are defined as nonscaffold molecules
-
Machine learning active-nematic hydrodynamics [Physics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jonathan Colen; Ming Han; Rui Zhang; Steven A. Redford; Linnea M. Lemma; Link Morgan; Paul V. Ruijgrok; Raymond Adkins; Zev Bryant; Zvonimir Dogic; Margaret L. Gardel; Juan J. de Pablo; Vincenzo Vitelli
Hydrodynamic theories effectively describe many-body systems out of equilibrium in terms of a few macroscopic parameters. However, such parameters are difficult to determine from microscopic information. Seldom is this challenge more apparent than in active matter, where the hydrodynamic parameters are in fact fields that encode the distribution of energy-injecting microscopic components. Here, we
-
Pericytes regulate vascular immune homeostasis in the CNS [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Orsolya Török; Bettina Schreiner; Johanna Schaffenrath; Hsing-Chuan Tsai; Upasana Maheshwari; Sebastian A. Stifter; Christina Welsh; Ana Amorim; Sucheta Sridhar; Sebastian G. Utz; Wiebke Mildenberger; Sina Nassiri; Mauro Delorenzi; Adriano Aguzzi; May H. Han; Melanie Greter; Burkhard Becher; Annika Keller
Pericytes regulate the development of organ-specific characteristics of the brain vasculature such as the blood–brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in the control of leukocyte trafficking in the adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using adult pericyte-deficient mice (Pdgfbret/ret), we show that
-
Raf promotes dimerization of the Ras G-domain with increased allosteric connections [Biophysics and Computational Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Morgan R. Packer; Jillian A. Parker; Jean K. Chung; Zhenlu Li; Young Kwang Lee; Trinity Cookis; Hugo Guterres; Steven Alvarez; Md Amin Hossain; Daniel P. Donnelly; Jeffrey N. Agar; Lee Makowski; Matthias Buck; Jay T. Groves; Carla Mattos
Ras dimerization is critical for Raf activation. Here we show that the Ras binding domain of Raf (Raf-RBD) induces robust Ras dimerization at low surface densities on supported lipid bilayers and, to a lesser extent, in solution as observed by size exclusion chromatography and confirmed by SAXS. Community network analysis based on molecular dynamics simulations shows robust allosteric connections linking
-
CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Simona Giunta; Solène Hervé; Ryan R. White; Therese Wilhelm; Marie Dumont; Andrea Scelfo; Riccardo Gamba; Cheng Kit Wong; Giulia Rancati; Agata Smogorzewska; Hironori Funabiki; Daniele Fachinetti
Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity to prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of the centromere-specific histone H3 variant CENP-A in safeguarding DNA replication of alpha-satellite repeats
-
Mesoscopic protein-rich clusters host the nucleation of mutant p53 amyloid fibrils [Chemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 David S. Yang; Arash Saeedi; Aram Davtyan; Mohsen Fathi; Michael B. Sherman; Mohammad S. Safari; Alena Klindziuk; Michelle C. Barton; Navin Varadarajan; Anatoly B. Kolomeisky; Peter G. Vekilov
The protein p53 is a crucial tumor suppressor, often called “the guardian of the genome”; however, mutations transform p53 into a powerful cancer promoter. The oncogenic capacity of mutant p53 has been ascribed to enhanced propensity to fibrillize and recruit other cancer fighting proteins in the fibrils, yet the pathways of fibril nucleation and growth remain obscure. Here, we combine immunofluorescence
-
Boronic acid with high oxidative stability and utility in biological contexts [Biochemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Brian J. Graham; Ian W. Windsor; Brian Gold; Ronald T. Raines
Despite their desirable attributes, boronic acids have had a minimal impact in biological contexts. A significant problem has been their oxidative instability. At physiological pH, phenylboronic acid and its boronate esters are oxidized by reactive oxygen species at rates comparable to those of thiols. After considering the mechanism and kinetics of the oxidation reaction, we reasoned that diminishing
-
Inhibition of neuroinflammatory nitric oxide signaling suppresses glycation and prevents neuronal dysfunction in mouse prion disease [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Julie-Myrtille Bourgognon; Jereme G. Spiers; Sue W. Robinson; Hannah Scheiblich; Paul Glynn; Catharine Ortori; Sophie J. Bradley; Andrew B. Tobin; Joern R. Steinert
Several neurodegenerative diseases associated with protein misfolding (Alzheimer’s and Parkinson’s disease) exhibit oxidative and nitrergic stress following initiation of neuroinflammatory pathways. Associated nitric oxide (NO)-mediated posttranslational modifications impact upon protein functions that can exacerbate pathology. Nonenzymatic and irreversible glycation signaling has been implicated as
-
Dysregulation of myelin synthesis and actomyosin function underlies aberrant myelin in CMT4B1 neuropathy [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Marta Guerrero-Valero; Federica Grandi; Silvia Cipriani; Valeria Alberizzi; Roberta Di Guardo; Gaetan Chicanne; Linda Sawade; Francesca Bianchi; Ubaldo Del Carro; Ivan De Curtis; Davide Pareyson; Yesim Parman; Angelo Schenone; Volker Haucke; Bernard Payrastre; Alessandra Bolino
Charcot-Marie-Tooth type 4B1 (CMT4B1) is a severe autosomal recessive demyelinating neuropathy with childhood onset, caused by loss-of-function mutations in the myotubularin-related 2 (MTMR2) gene. MTMR2 is a ubiquitously expressed catalytically active 3-phosphatase, which in vitro dephosphorylates the 3-phosphoinositides PtdIns3P and PtdIns(3,5)P2, with a preference for PtdIns(3,5)P2. A hallmark of
-
Pathogenic LRRK2 regulates ciliation probability upstream of tau tubulin kinase 2 via Rab10 and RILPL1 proteins [Medical Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Yuriko Sobu; Paulina S. Wawro; Herschel S. Dhekne; Wondwossen M. Yeshaw; Suzanne R. Pfeffer
Mutations that activate LRRK2 protein kinase cause Parkinson's disease. We showed previously that Rab10 phosphorylation by LRRK2 enhances its binding to RILPL1, and together, these proteins block cilia formation in a variety of cell types, including patient derived iPS cells. We have used live-cell fluorescence microscopy to identify, more precisely, the effect of LRRK2 kinase activity on both the
-
Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1 [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Pei-Yun Tsai; Min-Sik Lee; Unmesh Jadhav; Insia Naqvi; Shariq Madha; Ashley Adler; Meeta Mistry; Sergey Naumenko; Caroline A. Lewis; Daniel S. Hitchcock; Frederick R. Roberts; Peter DelNero; Thomas Hank; Kim C. Honselmann; Vicente Morales Oyarvide; Mari Mino-Kenudson; Clary B. Clish; Ramesh A. Shivdasani; Nada Y. Kalaany
Pancreatic ductal adenocarcinoma (PDA) is a lethal, therapy-resistant cancer that thrives in a highly desmoplastic, nutrient-deprived microenvironment. Several studies investigated the effects of depriving PDA of either glucose or glutamine alone. However, the consequences on PDA growth and metabolism of limiting both preferred nutrients have remained largely unknown. Here, we report the selection
-
In this issue Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-02 National Academy of Sciences
EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Rate-induced tipping point for overturning circulation Rapid increase in ice melt may push global ocean circulation past a tipping point. Image credit: Pixabay/Jeyaratnam Caniceus. With greenhouse gas concentrations increasing, several elements of the global climate system are at risk of crossing a tipping point that...
-
Correction for Abas et al., Naphthylphthalamic acid associates with and inhibits PIN auxin transporters [Corrections] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 National Academy of Sciences
PLANT BIOLOGY Correction for “Naphthylphthalamic acid associates with and inhibits PIN auxin transporters,” by Lindy Abas, Martina Kolb, Johannes Stadlmann, Dorina P. Janacek, Kristina Lukic, …
-
Profile of Michael Manga [Profiles] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Brian Doctrow
Geology is about more than just rocks and other hard objects. Fluids play a major role in shaping the surface of not just Earth but other planets and moons as well. In fact, according to Michael Manga, a geologist at the University of California, Berkeley, just about everything in Earth can be viewed as a fluid. “The atmosphere and the oceans are fluids,” he explains. “Volcanoes erupt magma, which
-
Correction for Moser et al., Cryo-SOFI enabling low-dose super-resolution correlative light and electron cryo-microscopy [Corrections] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 National Academy of Sciences
BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction for “Cryo-SOFI enabling low-dose super-resolution correlative light and electron cryo-microscopy,” by Felipe Moser, Vojtěch Pražák, Valerie Mordhorst, Débora M. Andrade, Lindsay A. Baker, Christoph Hagen, Kay Grünewald, and Rainer Kaufmann, which …
-
Correction for Kessler et al., De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population [Corrections] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 National Academy of Sciences
GENETICS Correction for “De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population,” by Michael D. Kessler, Douglas P. Loesch, James A. Perry, Nancy L. Heard-Costa, Daniel Taliun, Brian E. Cade, Heming Wang, Michelle Daya, John Ziniti, Soma Datta, Juan C. Celedón, Manuel E. Soto-Quiros, Lydiana Avila, Scott T. Weiss, …
-
Correction for Han et al., Mechanistic approaches for chemically modifying the coordination sphere of copper-amyloid-{beta} complexes [Corrections] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 National Academy of Sciences
CHEMISTRY, BIOCHEMISTRY Correction for “Mechanistic approaches for chemically modifying the coordination sphere of copper–amyloid-β complexes,” by Jiyeon Han, Hyuck Jin Lee, Kyu Yeon Kim, Geewoo Nam, Junghyun Chae, and Mi Hee Lim, which was first published February 26, 2020; 10.1073/pnas.1916944117 (Proc. …
-
Chemically controlled pattern formation in self-oscillating elastic shells [Applied Physical Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Siyu Li; Daniel A. Matoz-Fernandez; Aaveg Aggarwal; Monica Olvera de la Cruz
Patterns and morphology develop in living systems such as embryos in response to chemical signals. To understand and exploit the interplay of chemical reactions with mechanical transformations, chemomechanical polymer systems have been synthesized by attaching chemicals into hydrogels. In this work, we design autonomous responsive elastic shells that undergo morphological changes induced by chemical
-
Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis [Genetics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Pasquale Piccolo; Rosa Ferriero; Anna Barbato; Sergio Attanasio; Marcello Monti; Claudia Perna; Florie Borel; Patrizia Annunziata; Annamaria Carissimo; Rossella De Cegli; Luca Quagliata; Luigi M. Terracciano; Chantal Housset; Jeffrey H. Teckman; Christian Mueller; Nicola Brunetti-Pierri
α1-Antitrypsin (AAT) deficiency is a common genetic disease presenting with lung and liver diseases. AAT deficiency results from pathogenic variants in the SERPINA1 gene encoding AAT and the common mutant Z allele of SERPINA1 encodes for Z α1-antitrypsin (ATZ), a protein forming hepatotoxic polymers retained in the endoplasmic reticulum of hepatocytes. PiZ mice express the human ATZ and are a valuable
-
Evolution of Ycf54-independent chlorophyll biosynthesis in cyanobacteria [Plant Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Guangyu E. Chen; Andrew Hitchcock; Jan Mareš; Yanhai Gong; Martin Tichý; Jan Pilný; Lucie Kovářová; Barbora Zdvihalová; Jian Xu; C. Neil Hunter; Roman Sobotka
Chlorophylls (Chls) are essential cofactors for photosynthesis. One of the least understood steps of Chl biosynthesis is formation of the fifth (E) ring, where the red substrate, magnesium protoporphyrin IX monomethyl ester, is converted to the green product, 3,8-divinyl protochlorophyllide a. In oxygenic phototrophs, this reaction is catalyzed by an oxygen-dependent cyclase, consisting of a catalytic
-
A versatile platform for locus-scale genome rewriting and verification [Genetics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ran Brosh; Jon M. Laurent; Raquel Ordoñez; Emily Huang; Megan S. Hogan; Angela M. Hitchcock; Leslie A. Mitchell; Sudarshan Pinglay; John A. Cadley; Raven D. Luther; David M. Truong; Jef D. Boeke; Matthew T. Maurano
Routine rewriting of loci associated with human traits and diseases would facilitate their functional analysis. However, existing DNA integration approaches are limited in terms of scalability and portability across genomic loci and cellular contexts. We describe Big-IN, a versatile platform for targeted integration of large DNAs into mammalian cells. CRISPR/Cas9-mediated targeting of a landing pad
-
Spine dynamics of PSD-95-deficient neurons in the visual cortex link silent synapses to structural cortical plasticity [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Rashad Yusifov; Anja Tippmann; Jochen F. Staiger; Oliver M. Schlüter; Siegrid Löwel
Critical periods (CPs) are time windows of heightened brain plasticity during which experience refines synaptic connections to achieve mature functionality. At glutamatergic synapses on dendritic spines of principal cortical neurons, the maturation is largely governed by postsynaptic density protein-95 (PSD-95)-dependent synaptic incorporation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
-
N6-methyladenosine modification of HCV RNA genome regulates cap-independent IRES-mediated translation via YTHDC2 recognition [Microbiology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Geon-Woo Kim; Aleem Siddiqui
Hepatitis C virus (HCV) infections are associated with the risk of progression to fibrosis, cirrhosis, and hepatocellular carcinoma. The HCV RNA genome is translated by an internal ribosome entry site (IRES)-dependent mechanism. The structure and function of the HCV IRES have been investigated by both biological and biophysical criteria. Recently, the role of N6-methyladenosine (m6A) in cellular RNA