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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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...
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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, …
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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
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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 …
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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, …
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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. …
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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
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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
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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
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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
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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
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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
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mTORC1-chaperonin CCT signaling regulates m6A RNA methylation to suppress autophagy [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Hong-Wen Tang; Jui-Hsia Weng; Wen Xing Lee; Yanhui Hu; Lei Gu; Sungyun Cho; Gina Lee; Richard Binari; Cathleen Li; Min En Cheng; Ah-Ram Kim; Jun Xu; Zhangfei Shen; Chiwei Xu; John M. Asara; John Blenis; Norbert Perrimon
Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a central regulator of cell growth and metabolism that senses and integrates nutritional and environmental cues with cellular responses. Recent studies have revealed critical roles of mTORC1 in RNA biogenesis and processing. Here, we find that the m6A methyltransferase complex (MTC) is a downstream effector of mTORC1 during autophagy in Drosophila
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SUMO enables substrate selectivity by mitogen-activated protein kinases to regulate immunity in plants [Plant Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Vivek Verma; Anjil K. Srivastava; Catherine Gough; Alberto Campanaro; Moumita Srivastava; Rebecca Morrell; Joshua Joyce; Mark Bailey; Cunjin Zhang; Patrick J. Krysan; Ari Sadanandom
The versatility of mitogen-activated protein kinases (MAPKs) in translating exogenous and endogenous stimuli into appropriate cellular responses depends on its substrate specificity. In animals, several mechanisms have been proposed about how MAPKs maintain specificity to regulate distinct functional pathways. However, little is known of mechanisms that enable substrate selectivity in plant MAPKs.
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Posttranslational regulation of multiple clock-related transcription factors triggers cold-inducible gene expression in Arabidopsis [Plant Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Satoshi Kidokoro; Kentaro Hayashi; Hiroki Haraguchi; Tomona Ishikawa; Fumiyuki Soma; Izumi Konoura; Satomi Toda; Junya Mizoi; Takamasa Suzuki; Kazuo Shinozaki; Kazuko Yamaguchi-Shinozaki
Cold stress is an adverse environmental condition that affects plant growth, development, and crop productivity. Under cold stress conditions, the expression of numerous genes that function in the stress response and tolerance is induced in various plant species, and the dehydration-responsive element (DRE) binding protein 1/C-repeat binding factor (DREB1/CBF) transcription factors function as master
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Dual oxidase enables insect gut symbiosis by mediating respiratory network formation [Evolution] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Seonghan Jang; Peter Mergaert; Tsubasa Ohbayashi; Kota Ishigami; Shuji Shigenobu; Hideomi Itoh; Yoshitomo Kikuchi
Most animals harbor a gut microbiota that consists of potentially pathogenic, commensal, and mutualistic microorganisms. Dual oxidase (Duox) is a well described enzyme involved in gut mucosal immunity by the production of reactive oxygen species (ROS) that antagonizes pathogenic bacteria and maintains gut homeostasis in insects. However, despite its nonspecific harmful activity on microorganisms, little
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Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2 [Biochemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jingjing Pei; Nicole D. Wagner; Angela J. Zou; Srirupa Chatterjee; Dominika Borek; Aidan R. Cole; Preston J. Kim; Christopher F. Basler; Zbyszek Otwinowski; Michael L. Gross; Gaya K. Amarasinghe; Daisy W. Leung
Human respiratory syncytial virus (RSV) nonstructural protein 2 (NS2) inhibits host interferon (IFN) responses stimulated by RSV infection by targeting early steps in the IFN-signaling pathway. But the molecular mechanisms related to how NS2 regulates these processes remain incompletely understood. To address this gap, here we solved the X-ray crystal structure of NS2. This structure revealed a unique
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Anomalous mechanics of Zn2+-modified fibrin networks [Applied Physical Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jing Xia; Li-Heng Cai; Huayin Wu; Frederick C. MacKintosh; David A. Weitz
Fibrin is the main component of blood clots. The mechanical properties of fibrin are therefore of critical importance in successful hemostasis. One of the divalent cations released by platelets during hemostasis is Zn2+; however, its effect on the network structure of fibrin gels and on the resultant mechanical properties remains poorly understood. Here, by combining mechanical measurements with three-dimensional
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Comparative parallel analysis of RNA ends identifies mRNA substrates of a tRNA splicing endonuclease-initiated mRNA decay pathway [Genetics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Jennifer E. Hurtig; Michelle A. Steiger; Vinay K. Nagarajan; Tao Li; Ti-Chun Chao; Kuang-Lei Tsai; Ambro van Hoof
Eukaryotes share a conserved messenger RNA (mRNA) decay pathway in which bulk mRNA is degraded by exoribonucleases. In addition, it has become clear that more specialized mRNA decay pathways are initiated by endonucleolytic cleavage at particular sites. The transfer RNA (tRNA) splicing endonuclease (TSEN) has been studied for its ability to remove introns from pre-tRNAs. More recently it has been shown
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Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3 [Chemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Min Qiu; Zachary Glass; Jinjin Chen; Mary Haas; Xin Jin; Xuewei Zhao; Xuehui Rui; Zhongfeng Ye; Yamin Li; Feng Zhang; Qiaobing Xu
Loss-of-function mutations in Angiopoietin-like 3 (Angptl3) are associated with lowered blood lipid levels, making Angptl3 an attractive therapeutic target for the treatment of human lipoprotein metabolism disorders. In this study, we developed a lipid nanoparticle delivery platform carrying Cas9 messenger RNA (mRNA) and guide RNA for CRISPR-Cas9–based genome editing of Angptl3 in vivo. This system
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Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase/phosphatase, controls proliferation of the HCT116 tumor cell line [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Chunfang Gu; Juan Liu; Xiaojing Liu; Haibo Zhang; Ji Luo; Huanchen Wang; Jason W. Locasale; Stephen B. Shears
Identification of common patterns of cancer metabolic reprogramming could assist the development of new therapeutic strategies. Recent attention in this field has focused on identifying and targeting signal transduction pathways that interface directly with major metabolic control processes. In the current study we demonstrate the importance of signaling by the diphosphoinositol pentakisphosphate kinases
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A metapopulation model of social group dynamics and disease applied to Yellowstone wolves [Population Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ellen E. Brandell; Andrew P. Dobson; Peter J. Hudson; Paul C. Cross; Douglas W. Smith
The population structure of social species has important consequences for both their demography and transmission of their pathogens. We develop a metapopulation model that tracks two key components of a species’ social system: average group size and number of groups within a population. While the model is general, we parameterize it to mimic the dynamics of the Yellowstone wolf population and two associated
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Source apportionment of methane escaping the subsea permafrost system in the outer Eurasian Arctic Shelf [Earth, Atmospheric, and Planetary Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Julia Steinbach; Henry Holmstrand; Kseniia Shcherbakova; Denis Kosmach; Volker Brüchert; Natalia Shakhova; Anatoly Salyuk; Célia J. Sapart; Denis Chernykh; Riko Noormets; Igor Semiletov; Örjan Gustafsson
The East Siberian Arctic Shelf holds large amounts of inundated carbon and methane (CH4). Holocene warming by overlying seawater, recently fortified by anthropogenic warming, has caused thawing of the underlying subsea permafrost. Despite extensive observations of elevated seawater CH4 in the past decades, relative contributions from different subsea compartments such as early diagenesis, subsea permafrost
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HIV-1 cores retain their integrity until minutes before uncoating in the nucleus [Microbiology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Chenglei Li; Ryan C. Burdick; Kunio Nagashima; Wei-Shau Hu; Vinay K. Pathak
We recently reported that HIV-1 cores that retained >94% of their capsid (CA) protein entered the nucleus and disassembled (uncoated) near their integration site <1.5 h before integration. However, whether the nuclear capsids lost their integrity by rupturing or a small loss of CA before capsid disassembly was unclear. Here, we utilized a previously reported vector in which green fluorescent protein
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Structural basis for a bacterial Pip system plant effector recognition protein [Microbiology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Shukun Luo; Bruna G. Coutinho; Prikshat Dadhwal; Yasuhiro Oda; Jiahong Ren; Amy L. Schaefer; E. Peter Greenberg; Caroline S. Harwood; Liang Tong
A number of plant-associated proteobacteria have LuxR family transcription factors that we refer to as PipR subfamily members. PipR proteins play roles in interactions between bacteria and their plant hosts, and some are important for bacterial virulence of plants. We identified an ethanolamine derivative, N-(2-hydroxyethyl)-2-(2-hydroxyethylamino) acetamide (HEHEAA), as a potent effector of PipR-mediated
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Progenitor cell diversity in the developing mouse neocortex [Developmental Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Xiangbin Ruan; Bowei Kang; Cai Qi; Wenhe Lin; Jingshu Wang; Xiaochang Zhang
In the mammalian neocortex, projection neuron types are sequentially generated by the same pool of neural progenitors. How neuron type specification is related to developmental timing remains unclear. To determine whether temporal gene expression in neural progenitors correlates with neuron type specification, we performed single-cell RNA sequencing (scRNA-Seq) analysis of the developing mouse neocortex
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Host genetic control of natural killer cell diversity revealed in the Collaborative Cross [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Magali S. J. Dupont; Vincent Guillemot; Pascal Campagne; Nicolas Serafini; Solenne Marie; Xavier Montagutelli; James P. Di Santo; Christian A. J. Vosshenrich
Natural killer (NK) cells are innate effectors armed with cytotoxic and cytokine-secreting capacities whose spontaneous antitumor activity is key to numerous immunotherapeutic strategies. However, current mouse models fail to mirror the extensive immune system variation that exists in the human population which may impact on NK cell-based therapies. We performed a comprehensive profiling of NK cells
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Lipid droplets in mammalian eggs are utilized during embryonic diapause [Developmental Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Roberta Arena; Simona Bisogno; Łukasz Gąsior; Joanna Rudnicka; Laura Bernhardt; Thomas Haaf; Federica Zacchini; Michał Bochenek; Kinga Fic; Ewelina Bik; Małgorzata Barańska; Anna Bodzoń-Kułakowska; Piotr Suder; Joanna Depciuch; Artur Gurgul; Zbigniew Polański; Grażyna E. Ptak
Embryonic diapause (ED) is a temporary arrest of an embryo at the blastocyst stage when it waits for the uterine receptivity signal to implant. ED used by over 100 species may also occur in normally “nondiapausing” mammals when the uterine receptivity signal is blocked or delayed. A large number of lipid droplets (LDs) are stored throughout the preimplantation embryo development, but the amount of
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Simple stochastic model for geomagnetic excursions and reversals reproduces the temporal asymmetry of the axial dipole moment [Earth, Atmospheric, and Planetary Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Alberto Molina-Cardín; Luis Dinis; María Luisa Osete
We present a simple model for the axial dipole moment (ADM) of the geomagnetic field based on a stochastic differential equation for two coupled particles in a biquadratic potential, subjected to Gaussian random perturbations. This model generates aperiodic reversals and excursions separated by stable polarity periods. The model reproduces the temporal asymmetry of geomagnetic reversals, with slower
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TAp73 represses NF-{kappa}B-mediated recruitment of tumor-associated macrophages in breast cancer [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Johanna Wolfsberger; Habib A. M. Sakil; Leilei Zhou; Niek van Bree; Elena Baldisseri; Sabrina de Souza Ferreira; Veronica Zubillaga; Marina Stantic; Nicolas Fritz; Johan Hartman; Charlotte Rolny; Margareta T. Wilhelm
Infiltration of tumor-promoting immune cells is a strong driver of tumor progression. Especially the accumulation of macrophages in the tumor microenvironment is known to facilitate tumor growth and to correlate with poor prognosis in many tumor types. TAp73, a member of the p53/p63/p73 family, acts as a tumor suppressor and has been shown to suppress tumor angiogenesis. However, what role TAp73 has
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Genome-wide shifts in climate-related variation underpin responses to selective breeding in a widespread conifer [Genetics] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ian R. MacLachlan; Tegan K. McDonald; Brandon M. Lind; Loren H. Rieseberg; Sam Yeaman; Sally N. Aitken
Locally adapted temperate tree populations exhibit genetic trade-offs among climate-related traits that can be exacerbated by selective breeding and are challenging to manage under climate change. To inform climatically adaptive forest management, we investigated the genetic architecture and impacts of selective breeding on four climate-related traits in 105 natural and 20 selectively bred lodgepole
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ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development [Developmental Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Kaela M. Varberg; Khursheed Iqbal; Masanaga Muto; Mikaela E. Simon; Regan L. Scott; Keisuke Kozai; Ruhul H. Choudhury; John D. Aplin; Rebecca Biswell; Margaret Gibson; Hiroaki Okae; Takahiro Arima; Jay L. Vivian; Elin Grundberg; Michael J. Soares
Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast cell invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in mice identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development. We hypothesized that
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A multitaxa assessment of the effectiveness of agri-environmental schemes for biodiversity management [Agricultural Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Fabian A. Boetzl; Jochen Krauss; Jonathan Heinze; Hannes Hoffmann; Jan Juffa; Sebastian König; Elena Krimmer; Maren Prante; Emily A. Martin; Andrea Holzschuh; Ingolf Steffan-Dewenter
Agri-environmental schemes (AES) aim to restore biodiversity and biodiversity-mediated ecosystem services in landscapes impoverished by modern agriculture. However, a systematic, empirical evaluation of different AES types across multiple taxa and functional groups is missing. Within one orthogonal design, we studied sown flowering AES types with different temporal continuity, size, and landscape context
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Ozone pollution in the North China Plain spreading into the late-winter haze season [Earth, Atmospheric, and Planetary Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ke Li; Daniel J. Jacob; Hong Liao; Yulu Qiu; Lu Shen; Shixian Zhai; Kelvin H. Bates; Melissa P. Sulprizio; Shaojie Song; Xiao Lu; Qiang Zhang; Bo Zheng; Yuli Zhang; Jinqiang Zhang; Hyun Chul Lee; Su Keun Kuk
Surface ozone is a severe air pollution problem in the North China Plain, which is home to 300 million people. Ozone concentrations are highest in summer, driven by fast photochemical production of hydrogen oxide radicals (HOx) that can overcome the radical titration caused by high emissions of nitrogen oxides (NOx) from fuel combustion. Ozone has been very low during winter haze (particulate) pollution
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Human arrival and landscape dynamics in the northern Bahamas [Sustainability Science] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Patricia L. Fall; Peter J. van Hengstum; Lisa Lavold-Foote; Jeffrey P. Donnelly; Nancy A. Albury; Anne E. Tamalavage
The first Caribbean settlers were Amerindians from South America. Great Abaco and Grand Bahama, the final islands colonized in the northernmost Bahamas, were inhabited by the Lucayans when Europeans arrived. The timing of Lucayan arrival in the northern Bahamas has been uncertain because direct archaeological evidence is limited. We document Lucayan arrival on Great Abaco Island through a detailed
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Nonthermal and reversible control of neuronal signaling and behavior by midinfrared stimulation [Neuroscience] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Xi Liu; Zhi Qiao; Yuming Chai; Zhi Zhu; Kaijie Wu; Wenliang Ji; Daguang Li; Yujie Xiao; Lanqun Mao; Chao Chang; Quan Wen; Bo Song; Yousheng Shu
Various neuromodulation approaches have been employed to alter neuronal spiking activity and thus regulate brain functions and alleviate neurological disorders. Infrared neural stimulation (INS) could be a potential approach for neuromodulation because it requires no tissue contact and possesses a high spatial resolution. However, the risk of overheating and an unclear mechanism hamper its application
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Cysteinyl-specialized proresolving mediators link resolution of infectious inflammation and tissue regeneration via TRAF3 activation [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Nan Chiang; Xavier de la Rosa; Stephania Libreros; Hui Pan; Jonathan M. Dreyfuss; Charles N. Serhan
The recently elucidated proresolving conjugates in tissue regeneration (CTR) maresin-CTR (MCTR), protectin-CTR (PCTR), and resolvin-CTR (RCTR), termed cysteinyl-specialized proresolving mediators (cys-SPMs) each promotes regeneration, controls infection, and accelerates resolution of inflammation. Here, we sought evidence for cys-SPM activation of primordial pathways in planaria (Dugesia japonica)
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Structural insights into {alpha}-synuclein monomer-fibril interactions [Biochemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Pratibha Kumari; Dhiman Ghosh; Agathe Vanas; Yanick Fleischmann; Thomas Wiegand; Gunnar Jeschke; Roland Riek; Cédric Eichmann
Protein aggregation into amyloid fibrils is associated with multiple neurodegenerative diseases, including Parkinson’s disease. Kinetic data and biophysical characterization have shown that the secondary nucleation pathway highly accelerates aggregation via the absorption of monomeric protein on the surface of amyloid fibrils. Here, we used NMR and electron paramagnetic resonance spectroscopy to investigate
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Stunted upward mobility in a learning environment reduces the academic benefits of growth mindsets [Psychological and Cognitive Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Lile Jia; Chun Hui Lim; Ismaharif Ismail; Yia Chin Tan
Does stunted upward mobility in an educational system impede beneficial psychological processes of learning? We predicted that growth mindsets of intelligence, a well-established psychological stimulant to learning, would be less potent in low-mobility, as compared to high-mobility, learning environments. An analysis of a large cross-national dataset and a longitudinal experiment accumulated converging
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Do conversations end when people want them to? [Psychological and Cognitive Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Adam M. Mastroianni; Daniel T. Gilbert; Gus Cooney; Timothy D. Wilson
Do conversations end when people want them to? Surprisingly, behavioral science provides no answer to this fundamental question about the most ubiquitous of all human social activities. In two studies of 932 conversations, we asked conversants to report when they had wanted a conversation to end and to estimate when their partner (who was an intimate in Study 1 and a stranger in Study 2) had wanted
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Mutational fitness landscapes reveal genetic and structural improvement pathways for a vaccine-elicited HIV-1 broadly neutralizing antibody [Applied Biological Sciences] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Bharat Madan; Baoshan Zhang; Kai Xu; Cara W. Chao; Sijy O’Dell; Jacy R. Wolfe; Gwo-Yu Chuang; Ahmed S. Fahad; Hui Geng; Rui Kong; Mark K. Louder; Thuy Duong Nguyen; Reda Rawi; Arne Schön; Zizhang Sheng; Rajani Nimrania; Yiran Wang; Tongqing Zhou; Bob C. Lin; Nicole A. Doria-Rose; Lawrence Shapiro; Peter D. Kwong; Brandon J. DeKosky
Vaccine-based elicitation of broadly neutralizing antibodies holds great promise for preventing HIV-1 transmission. However, the key biophysical markers of improved antibody recognition remain uncertain in the diverse landscape of potential antibody mutation pathways, and a more complete understanding of anti–HIV-1 fusion peptide (FP) antibody development will accelerate rational vaccine designs. Here
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IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease [Immunology and Inflammation] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Ji-Min Ju; Giri Nam; Young-Kwan Lee; Minho Jung; Hanna Chang; Woojin Kim; Woo Jeong Shon; Ji Young Lim; Joo Young Kim; Jun Chang; Chang Ki Min; Dong-Sup Lee; Kyungho Choi; Dong-Mi Shin; Eun Young Choi
Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying
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The store-operated Ca2+ entry complex comprises a small cluster of STIM1 associated with one Orai1 channel [Cell Biology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Yihan Shen; Nagendra Babu Thillaiappan; Colin W. Taylor
Increases in cytosolic Ca2+ concentration regulate diverse cellular activities and are usually evoked by opening of Ca2+ channels in intracellular Ca2+ stores and the plasma membrane (PM). For the many signals that evoke formation of inositol 1,4,5-trisphosphate (IP3), IP3 receptors coordinate the contributions of these two Ca2+ sources by mediating Ca2+ release from the endoplasmic reticulum (ER)
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Evolutionary relationships between drought-related traits and climate shape large hydraulic safety margins in western North American oaks [Ecology] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Robert P. Skelton; Leander D. L. Anderegg; Jessica Diaz; Matthew M. Kling; Prahlad Papper; Laurent J. Lamarque; Sylvain Delzon; Todd E. Dawson; David D. Ackerly
Quantitative knowledge of xylem physical tolerance limits to dehydration is essential to understanding plant drought tolerance but is lacking in many long-vessel angiosperms. We examine the hypothesis that a fundamental association between sustained xylem water transport and downstream tissue function should select for xylem that avoids embolism in long-vessel trees by quantifying xylem capacity to
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Three-step nucleation of metal-organic framework nanocrystals [Chemistry] Proc. Natl. Acad. Sci. U.S.A. (IF 9.412) Pub Date : 2021-03-09 Xiangwen Liu; See Wee Chee; Sanoj Raj; Michal Sawczyk; Petr Král; Utkur Mirsaidov
Metal–organic frameworks (MOFs) are crystalline nanoporous materials with great potential for a wide range of industrial applications. Understanding the nucleation and early growth stages of these materials from a solution is critical for their design and synthesis. Despite their importance, the pathways through which MOFs nucleate are largely unknown. Using a combination of in situ liquid-phase and