Fibro-inflammatory progenitors represent a subpopulation of perivascular cells in visceral adipose tissues of mice that promote inflammation and fibrosis.
Kira M Düsterwald, Christopher B Currin ... Joseph V Raimondo
Mathematical models with experimental validation show that chloride transporters in the cell membrane, and not negatively charged impermeant molecules, generate the driving force used by GABA receptors to silence neurons.
Oliver Gordon, Conor M Henry ... Caetano Reis e Sousa
The Drosophila response to injection of alpha-actinin reinforces the notion that exposure of cytoskeletal components acts as a sign of cell damage conserved throughout metazoan evolution.
The scaffolding protein Oskar organizes two types of germ granules by phase transition within the same cell but with distinct morphologies, composition and biological functions.
Tineke Grent-'t-Jong, Joachim Gross ... Peter J Uhlhaas
Resting-state MEG-activity and MRS-GABA/Glx measurements reveal that there is a significant shift in excitability during the course of schizophrenia, involving hyperexcitability during the onset and a reduction at chronic stages.
Cameron C Scott, Stefania Vossio ... Jean Gruenberg
The biogenesis of lipid droplets induced by Wnt3a is controlled by the transcription factor TFAP2, which presumably acts as a 'master' regulator of lipid droplet biogenesis.
Sodium ions control the rates of both substrate binding and dissociation of an archaeal homologue of glutamate transporters in a manner that minimizes binding intermediates and maximizes transport efficiency.
Par3 is polarized in the plane of the vertebrate neural plate, binds and recruits Prickle3 to the apical membrane and promotes the formation of core planar cell polarity complexes.
Feedback sensing of the intracellular calcium concentration suffices to reproduce the diversity of ionic conductances underlying normal cardiac electromechanical function in a genetically diverse population of mice.
The glycine T-box riboswitch recognizes tRNAgly and senses its aminoacylation state by first interacting with the anticodon region and subsequently probing the 3' end of the ligand using both specific structural elements and conformational dynamics.
Brian T Emmer, Geoffrey G Hesketh ... David Ginsburg
A CRISPR-based genomic screen identifies the ER cargo receptor SURF4 as a key determinant in the secretion of PCSK9, a protein that regulates human cholesterol levels and cardiovascular disease risk.
The first structure of the human epithelial sodium channel provides vital insight into the assembly, stoichiometry and molecular mechanism of the ion channel central to sodium homeostasis.
Simultaneous EEG-fMRI reveals neural representations of decision confidence unfolding prior to explicit perceptual choices, in a region of the ventromedial prefrontal cortex typically linked to reward processing and value-based decisions.
Acute hypoxia activates TRPA1 channels in cerebral artery endothelial cells to activate an early adaptive response to reduce tissue ischemic damage through vasodilation.
Katherine A Smith, Stephan Löser ... Rick M Maizels
Immune expulsion of helminth parasites is driven by two key pathways mediated by soluble cytokines ligating to the IL-4 and IL-25 receptors acting on innate effector cells throughout the course of infection.
Ezrin, an important actin-membrane linker, can zip adjacent membranes, be enriched to positively-curved membranes when phosphorylated and to negatively-curved membranes through a direct interaction with membrane curvature sensor I-BAR domain proteins.
Zoé Vincent-Mistiaen, Ahmed Elbediwy ... Barry Thompson
High levels of nuclear YAP are sufficient to drive squamous cell carincoma formation and frequently also drive progression to spindle cell carcinoma by promoting epithelial-to-mesenchymal transition after tissue damage.
Jimmie M Gmaz, James E Carmichael, Matthijs AA van der Meer
Neural activity in the rat nucleus accumbens provides a rich task representation that includes not only expected outcomes, but also the specific identity of the cues that predict these outcomes.
Modifying the recurrent connectivity of spiking networks provides sufficient flexibility to generate arbitrarily complex recurrent dynamics, suggesting that individual neurons in a recurrent network have the capability to support near universal dynamics.
Neus Martínez-Abadías, Roger Mateu Estivill ... James Sharpe
Quantitative analyses associating the morphology of developing organs with dynamic gene expression patterns can reveal biological phenomena that cause malformations and malfunction but remain elusive to traditional qualitative assessments.
Cereblon-based small-molecule degraders rely on the sequential action of ubiquitin-conjugating enzymes UBE2G1 and UBE2D3 to assemble K48-linked polyubiquitin chains on cereblon neomorphic substrates, resulting in their proteasomal degradation.
Hygroreception, a poorly understood process critical to insect survival, depends on a small protein in the antenna of the fruit fly that was previously thought to transport odorants.
Clémence Hocquet, Xavier Robellet ... Pascal Bernard
Contrary to the generally accepted model, condensin maintains proper gene expression by promoting the accurate segregation of chromosomes and the partitioning of the RNA-exosome throughout mitosis, instead of directly regulating transcription.
Analysis of the endogenous function of deeply conserved neuropeptides in sea anemones sheds light on a primitive role of nervous systems in modulating developmental timing.
John B Lees-Shepard, Sarah-Anne E Nicholas ... David J Goldhamer
Daily palovarotene treatment reduces pathogenic expansion of fibro/adipogenic progenitors but results in long bone growth plate loss and overgrowths of synovial cartilage in juvenile mice.
The machinery that carries out programmed DNA rearrangements is composed of domesticated transposases. One is catalytically active, five play architectural function essential for the accuracy of the process.
Genetic predisposition to uterine leiomyomas arises from variation at loci for genetic stability and genitourinary development, and in part explains the frequent occurrence of the condition in women with African origin.
Aaron G Wexler, Whitman B Schofield ... Andrew L Goodman
The human gut bacterial lipoprotein BtuG binds vitamin B12 with femtomolar affinity, can remove vitamin B12 from human intrinsic factor, and is required for commensal fitness in the gut.
Inés Martínez, Maria X Maldonado-Gomez ... Jens Walter
Experiments in ex-germ-free mice establish a measurable effect of colonization history on gut microbiota assembly, illuminating a potential cause for the high levels of unexplained individuality in host-associated microbial communities.
Firas Bou Daher, Yuanjie Chen ... Siobhan A Braybrook
Growing upwards in the young seedling is controlled by two cooperative mechanical mechanisms: cellulose orientation in inner tissues and differential elasticity in epidermal cells.
Computational model reveals how the fast exchange of neurotransmitter receptors between synapses induces a competition leading to a transient form of heterosynaptic plasticity and shaping the induction of homosynaptic plasticity.
Head-direction cells in the parahippocampal region can be divided into two functionally distinct classes that are differentially constrained by attractor network dynamics.
Judith Gunzelmann, Diana Rüthnick ... Elmar Schiebel
Biochemical and genetic approaches show that the XMAP215 homolog Stu2 directly interacts with the small gamma-tubulin complex and its recruitment factor Spc72 to instigate functions in cytoplasmic microtubule organization.
Mathematical and experimental analyses suggest that despite their complex architectures, multiple metazoan signaling pathways act in physiological contexts as linear signal transmitters.
Daiane S Alves, Justin M Westerfield ... Francisco N Barrera
The transmembrane domain of the EphA2 receptor has been transformed into a novel amphitropic peptide that binds to the EphA2 receptor and inhibits cell migration.
Analysis of the global genetic requirements and gene expression changes in E. coli in the presence of a simple microbiome revealed pairwise and higher-order interactions, and underlying molecular mechanisms.
Retrograde transport of NT-3 stimulated the reorganization of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, along with improved behavioral recovery.
Ultrastructural and loss-of-function experiments show that oligodendrocyte-encoded Kir4.1 is located near active axonal structures, including within myelin inner tongue, and has critical functions to promote axonal activity and preserve integrity.
Adult male, but not female, rats showed altered neuronal function, inhibited synaptic plasticity and diminished social behavior following cannabinoid exposure during gestation in a model of cannabis use during pregnancy.
Pulsed-labeling hydrogen exchange on the ribonuclease H family show that the major folding intermediate is conserved over three billion years of evolution, but the path leading to this intermediate varies.
Azadeh Seidi, Linden S Muellner-Wong ... Giel G van Dooren
The proteins found in the mitochondria of apicomplexan parasites, including key proteins involved in energy generation, are very different from mitochondrial proteins of the animals these parasites infect.
Manuel Jiménez-Zaragoza, Marina PL Yubero ... Javier M Rodríguez
In triple-layered rotavirus particles, strong interaction between the external and middle layers provides high mechanical strength for protection tasks, while weaker interaction between the middle and inner layers favors transcription.
Standing genetic variation for disease resistance may be continuously lost during recurring warm water episodes because of widespread susceptibility of disease-resistant genotypes to bleaching and the independence between these two traits.
Oleg Tolstenkov, Petrus Van der Auwera ... Alexander Gottschalk
The 'missing' class of Caenorhabditis elegans excitatory motor neurons, AS, contribute to propagation and coordination of body waves, integrating information from, and feeding back to premotor interneurons byelectrical signaling.
Electron-cryomicroscopy structures of the supercomplex of NSF, αSNAP, and neuronal SNAREs in the presence of ATP under non-hydrolyzing conditions at 3.9 Å resolution reveal interactions between the N-terminal residues of SNAP-25 and NSF.
Christina Zakas, Jennifer M Deutscher ... Matthew V Rockman
Early development involves both maternal and zygotic genetic effects. This dual genetic basis shapes the evolution of developmental mode in a marine annelid.
Two structurally-unrelated regulatory proteins utilize parallel molecular mechanisms to selectively tune calcium and calmodulin feedback of calcium and sodium ion channels and reveals a novel strategy to engineer synthetic channel modulators.
Trevor R Sorrells, Amanda N Johnson ... Alexander D Johnson
Cooperativity between two transcription regulators occurs through protein-protein interactions with a general transcription factor complex and potentiates the parallel evolution of their DNA binding sites.
Myron S Ignatius, Madeline N Hayes ... David M Langenau
Syngeneic tp53-null zebrafish develop a wide range of tumors that engraft into recipient animals with loss of Tp53 leading to increased metastasis in embryonal rhabdomyosarcoma (ERMS), likely accounting for increased aggression in TP53-inactivated human ERMS.
Light signaling components interact with a histone H2B deubiquitination module, adjusting chromatin states at global level during Arabidopsis seedling development.
Leon Y Chan, Christopher F Mugler ... Karsten Weis
Non-invasive mRNA stability measurements reveal that transcript lifetime is governed by a competition with translation initiation on a transcriptome-wide level.
In the retina, the receptive field surround preserves the spatial contrast sensitivity of the center in the face of naturalistic changes in local luminance.
Federico Andrea Moretti, Sarah Klapproth ... Markus Moser
T cell progenitor homing into the thymus requires kindlin-3 to stabilize their adhesion to vascular integrin ligands when blood flow velocities and shear rates increase during development.
Angela M Phillips, Michael B Doud ... Matthew D Shoulders
Endoplasmic reticulum proteostasis factors enhance the mutational tolerance of influenza hemagglutinin, a model secretory pathway protein and therapeutic target, particularly improving the fitness of temperature-sensitive variants.
Genome-wide integration of transcriptome, accessible chromatin, and DNA methylome data from vascular endothelial cells lays the foundation for understanding the gene regulatory circuits that generate organ-specific vascular specialization.
Heterodyne low-coherence interferometry demonstrates that the latency of the sound-induced reticular lamina vibration is significantly greater than that of the basilar membrane vibration in living gerbil cochleae.
Cindy Dirscherl, Zeynep Hein ... Sebastian Springer
A generally applicable two-hybrid assay demonstrates that MHC class I heavy chains devoid of beta-2 microglobulin associate within and across allotypes, with implications for endocytosis and autoimmunity.
Temperature and ionic conditions control the mechanical properties of virally encapsidated DNA and act as a switch between synchronized and desynchronized genome ejection dynamics in a phage population.
Remaining focused on the topic at hand when speaking depends on effective selection of task-relevant semantic knowledge, and declines in this ability account for increases in off-topic speech in older people.
Romain Durand-de Cuttoli, Sarah Mondoloni ... Alexandre Mourot
In vivo deconstruction of reward-related behaviors with circuit and pharmacological specificity using designer, light-controllable nicotinic acetylcholine receptors.
Isabelle Arnoux, Michael Willam ... Albrecht Stroh
In a premanifest mouse model of Huntington's disease at a stage very far from disease onset, significant network and behavior dysregulation was found, being rebalanced by treatment with metformin.
Jakob Nikolas Kather, Meggy Suarez-Carmona ... Niels Halama
Spatial patterns of lymphoid and myeloid cells in human solid tumors differ between cancer types, yielding a new classification of anti-tumor host response.
The retromer complex serves as a bomb squad to retrieve and disarm the potentially harmful pool of Notch receptors in a timely manner and thereby safeguards against brain tumor formation.
The BB model explains spatial cognition in terms of interactions between specific neuronal populations, providing a common computational framework for the human neuropsychological and in vivo animal electrophysiological literatures.
Lineage tracing using a knockin Pdgfra-rtTA tool indicates distinct contributions of this cell lineage to myofibroblasts in normal development, fibrosis and bronchopulmonary dysplasia models.
Haley Hieronymus, Rajmohan Murali ... Charles L Sawyers
The percentage of a tumor’s genome with alterations in copy number is correlated with increased mortality across a range of tumor types and can be measured using a clinically approved sequencing assay.
Cristiano Alessandro, Benjamin A Rellinger ... Matthew C Tresch
The adaptation strategy used by the nervous system following muscle paralysis restores task performance while minimizing the stresses and strains within a joint.
