bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions between the N- and C- termini of mechanosensitive ion channel AtMSL10 are consistent with a three-step mechanism for activation
Authors: Basu Debarati , Shoots Jennette M. , Haswell Elizabeth S. 
Published: August 2019

ABSTRACTAlthough a growing number of mechanosensitive ion channels are being identified in plant systems, the molecular mechanisms by which they function are still under investigation. Overexpression of the mechanosensitive ion channel MSL (MscS-Like)10 fused to GFP triggers a number of developmental and cellular phenotypes including the induction of cell death, and this function is influenced by seven phosphorylation sites in its soluble N-terminus. Here, we show that these and other phenotypes required neither overexpression nor a tag and could be also induced by a previously identified point mutation in the soluble C-terminus (S640L). The promotion of cell death and hyperaccumulation of H2O2 in 35S:MSL10S640L-GFP overexpression lines was suppressed by N-terminal phosphomimetic substitutions, and the soluble N- and C-terminal domains of MSL10 physically interacted. We propose a three-step model by which tension-induced conformational changes in the C-terminus are transmitted to the N-terminus, leading to its dephosphorylation and the induction of adaptive responses. Taken together, this work expands our understanding of the molecular mechanisms of mechanotransduction in plants.HIGHLIGHTCell death is triggered by mutations in either the cytoplasmic N- or C-terminus of AìMSLlü. Our proposed model explains how membrane tension may activate signaling through the interaction of these two domains.
sumrep: a summary statistic framework for immune receptor repertoire comparison and model validation
Authors: Olson Branden J , Moghimi Pejvak , Schramm Chaim , Obraztsova Anna , Ralph Duncan , Vander Heiden Jason A , Shugay Mikhail , Shepherd Adrian , Lees William , Matsen Frederick A 
Published: August 2019

AbstractThe adaptive immune system generates an incredible diversity of antigen receptors for B and T cells to keep dangerous pathogens at bay. The DNA sequences coding for these receptors arise by a complex recombination process followed by a series of productivity-based filters, as well as affinity maturation for B cells, giving considerable diversity to the circulating pool of receptor sequences. Although these datasets hold considerable promise for medical and public health applications, the complex structure of the resulting adaptive immune receptor repertoire sequencing (AIRR-seq) datasets makes analysis difficult. In this paper we introducesumrep, an R package that efficiently performs a wide variety of repertoire summaries and comparisons, and show howsumrepcan be used to perform model validation. We find that summaries vary in their ability to differentiate between datasets, although many are able to distinguish between covariates such as donor, timepoint, and cell type for BCR and TCR repertoires. We show that deletion and insertion lengths resulting from V(D)J recombination tend to be more discriminative characterizations of a repertoire than summaries that describe the amino acid composition of the CDR3 region. We also find that state-of-the-art generative models excel at recapitulating gene usage and recombination statistics in a given experimental repertoire, but struggle to capture many physiochemical properties of real repertoires.
Isolation and characterisation of novel phages infectingLactobacillus plantarumand proposal of a new genus, “Silenusvirus”
Authors: Kyrkou Ifigeneia , Carstens Alexander Byth , Ellegaard-Jensen Lea , Kot Witold , Zervas Athanasios , Djurhuus Amaru Miranda , Neve Horst , Franz Charles M.A.P. , Hansen Martin , Hansen Lars Hestbjerg 
Published: August 2019

ABSTRACTBacteria ofLactobacillussp. are very useful to humans. However, the biology and genomic diversity of their (bacterio)phage enemies remains understudied. Knowledge onLactobacillusphage diversity should broaden to develop efficient phage control strategies. To this end, organic waste samples were screened for phages against two wine-relatedLactobacillus plantarumstrains. Isolates were shotgun sequenced and compared against the phage database and each other by phylogenetics and comparative genomics. The new isolates had only three distant relatives from the database but displayed a high overall degree of genomic similarity amongst them. The latter allowed for the use of one isolate as a representative to conduct transmission electron microscopy and structural protein sequencing, and to study phage adsorption and growth kinetics. The microscopy and proteomics tests confirmed the observed diversity of the new isolates and supported their classification to the familySiphoviridaeand the proposal of the new phage genus “Silenusvirus”.
Characterization of evolutionarily conserved key players affecting eukaryotic flagellar motility and fertility using a moss model
Authors: Meyberg Rabea , Perroud Pierre-François , Haas Fabian B. , Schneider Lucas , Heimerl Thomas , Renzaglia Karen , Rensing Stefan A. 
Published: August 2019

AbstractDefects in flagella/cilia are often associated with infertility and disease. Motile male gametes (sperm cells) with flagella are an ancestral eukaryotic trait that has been lost in several lineages, for example in flowering plants. Here, we made use of a phenotypic male fertility difference between two moss (Physcomitrella patens) strains to explore spermatozoid function. We compare genetic and epigenetic variation as well as expression profiles between the Gransden and Reute strain to identify a set of genes associated with moss male infertility. Defects in mammal and algal homologs of these genes coincide with a loss of fertility, demonstrating the evolutionary conservation of flagellar function related to male fertility across kingdoms. As a proof of principle, we generated a loss-of-function mutant of a coiled-coil domain containing 39 (ccdc39) gene that is part of the flagellar hydin network. Indeed, the Ppccdc39 mutant resembles the male infertile Gransden strain phenotype. Potentially, several somatic (epi-)mutations occurred during prolonged vegetative propagation of P. patens Gransden, causing regulatory differences of e.g. the homeodomain transcription factor BELL1. Probably these somatic changes are causative for the observed male fertility. We propose that P. patens spermatozoids might be employed as an easily accessible system to study male infertility of human and animals.
Commensal bacteria differentially shape the nutritional requirements ofDrosophiladuring juvenile growth
Authors: Consuegra Jessika , Grenier Théodore , Baa-Puyoulet Patrice , Rahioui Isabelle , Akherraz Houssam , Gervais Hugo , Parisot Nicolas , da Silva Pedro , Charles Hubert , Calevro Federica , Leulier François 
Published: August 2019

AbstractThe interplay between nutrition and the microbial communities colonizing the gastro-intestinal tract (i.e. gut microbiota) determines juvenile growth trajectory. Nutritional deficiencies trigger developmental delays, and an immature gut microbiota is a hallmark of pathologies related to childhood undernutrition. However, how commensal bacteria modulate the impact of nutrition on juvenile growth remains elusive. Here, using gnotobioticDrosophila melanogasterlarvae independently associated with two model commensal bacterial strains,Acetobacter pomorumWJL(ApWJL) andLactobacillus plantarumNC8(LpNC8), we performed a large-scale, systematic nutritional screen based on larval growth in 40 different and precisely controlled nutritional environments. We combined these results with genome-based metabolic network reconstruction to define the biosynthetic capacities ofDrosophilagerm-free (GF) larvae and its two commensal bacteria. We first established that ApWJLand LpNC8differentially fulfills the nutritional requirements of the ex-GF larvae and parsed such difference down to individual amino acids, vitamins, other micronutrients and trace metals. We found thatDrosophilacommensal bacteria not only fortify the host’s diet with essential nutrients but, in specific instances, functionally compensate for host auxotrophies, by either providing a metabolic intermediate or nutrient derivative to the host or by uptaking, concentrating and sparing contaminant traces of micronutrients. Our systematic work reveals that, beyond the molecular dialogue engaged between the host and its commensal partners,Drosophilaand its facultative bacterial partners establish an integrated nutritional network relying on nutrients sparing and utilization.
A role for astroglial calcium in mammalian sleep
Authors: Ingiosi Ashley M. , Hayworth Christopher R. , Harvey Daniel O. , Singletary Kristan G. , Rempe Michael J. , Wisor Jonathan P. , Frank Marcos G. 
Published: August 2019

AbstractMammalian sleep is characterized by dramatic changes in neuronal activity, and waking neuronal activity is thought to increase sleep need. Changes in other brain cells (glia) across the natural sleep-wake cycle and their role in sleep regulation are comparatively unexplored. We show that sleep is also accompanied by large changes in astroglial activity as measured by intracellular calcium concentrations in unanesthetized mice. These changes in calcium vary across different vigilance states and are most pronounced in distal astroglial processes. We find that reducing intracellular calcium in astrocytes impaired the homeostatic response to sleep deprivation. Thus, astroglial calcium changes dynamically across vigilance states and is a component of the sleep homeostat.One Sentence SummaryAstroglial calcium concentrations vary with sleep and wake, change after sleep deprivation, and mediate sleep need.
Timing and original features of flagellum assembly in trypanosomes during development in the tsetse fly
Authors: Lemos Moara , Mallet Adeline , Bertiaux Eloïse , Imbert Albane , Rotureau Brice , Bastin Philippe 
Published: August 2019

AbstractTrypanosoma bruceiexhibits a complex life cycle alternating between tsetse flies and mammalian hosts. When parasites infect the fly, cells differentiate to adapt to life in various tissues, which is accompanied by drastic morphological and biochemical modifications especially in the proventriculus. This key step represents a bottleneck for salivary gland infection. Here we monitored flagellum assembly in trypanosomes during differentiation from the trypomastigote to the epimastigote stage, i.e. when the nucleus migrates to the posterior end of the cell. Three-dimensional electron microscopy (Focused Ion Bean Scanning Electron Microscopy, FIB-SEM) and immunofluorescence assays provided structural and molecular evidence that the new flagellum is assembled while the nucleus migrates towards the posterior region of the body. Two major differences with well known procyclic cells are reported. First, growth of the new flagellum begins when the associated basal body is found in a posterior position relative to the mature one. Second, the new flagellum acquires its own flagellar pocket before rotating on the left side of the anterior-posterior axis. FIB-SEM revealed the presence of a structure connecting the new and mature flagellum and serial sectioning confirmed morphological similarities with the flagella connector of procyclic cells. We discuss potential function of the flagella connector in trypanosomes from the proventriculus. These findings show thatT. bruceifinely modulates its cytoskeletal components to generate highly variable morphologies.Author SummaryTrypanosoma bruceiis a flagellated parasitic protist that causes human African trypanosomiasis, or sleeping sickness and that is transmitted by the bite of tsetse flies. The complex life cycle ofT. bruceiinside the tsetse digestive tract requires adaptation to specific organs and follow a strictly defined order. It is marked by morphological modifications in cell shape and size, as well organelle positioning. In the proventriculus of tsetse flies,T. bruceiundergoes a unique asymmetric division leading to two very different daughter cells: one with a short and one with a long flagellum. This organelle is crucial for the trypanosome life cycle as it is involved in motility, adhesion and morphogenesis. Here we investigated flagellum assembly using molecular and 3D Electron Microscopy approaches revealing that flagellum construction in proventricular trypanosomes is concomitant with parasite differentiation. During flagellum growth, the new flagellum is connected to the mature one and rotates around the mature one after its emergence at the cell surface. The sequence of events is different from what is observed in the well-studied procyclic stage in culture revealing different processes governing morphological development. These results highlight the importance to study pathogen development in their natural environment.
Modelling Osteocyte Network Formation: Healthy and Cancerous Environments
Authors: Taylor-King Jake P. , Buenzli Pascal R. , Chapman S. Jon , Lynch Conor C. , Basanta David 
Published: August 2019

AbstractAdvanced cancers, such as prostate and breast cancers, commonly metastasize to bone. In the bone matrix, dendritic osteocytes form a spatial network allowing communication between osteocytes and the osteoblasts located on the bone surface. This communication network facilitates coordinated bone remodelling. In the presence of a cancerous microenvironment, the morphology of this network changes. Commonly osteocytes appear to be either overdifferentiated (i.e., there are more dendrites than healthy bone) or underdeveloped (i.e., dendrites do not fully form). In addition to structural changes, histological sections from metastatic breast cancer xenografted mice show that number of osteocytes per unit area is different between healthy bone and cancerous bone. We present a stochastic agent-based model for bone formation incorporating osteoblasts and osteocytes that allows us to probe both network structure and density of osteocytes in bone. Our model both allows for the simulation of our spatial network model and analysis of mean-field equations in the form of integro-partial differential equations. We considered variations of our model to study specific physiological hypotheses related to osteoblast differentiation; for example predicting how changing biological parameters, such as rates of bone secretion, rates of cancer formation and rates of osteoblast differentiation can allow for qualitatively different network morphologies. We then used our model to explore how commonly applied therapies such as bisphosphonates (e.g. zoledronic acid) impact osteocyte network formation.
Development of an N-Cadherin Biofunctionalized Hydrogel to Support the Formation of Synaptically Connected Neural Networks
Authors: O’Grady Brian J. , Balotin Kylie M. , Bosworth Allison M. , McClatchey P. Mason , Weinstein Robert M. , Gupta Mukesh , Poole Kara S. , Bellan Leon M. , Lippmann Ethan S. 
Published: August 2019

AbstractIn vitro models of the human central nervous system (CNS), particularly those derived from induced pluripotent stem cells (iPSCs), are becoming increasingly recognized as useful complements to animal models for studying neurological diseases and developing therapeutic strategies. However, current 3D CNS models suffer from deficits that limit their research utility. Notably, it remains difficult to drive iPSC-derived neurons to a mature and synaptically connected state. Moreover, the most common extracellular matrices (ECMs) used to fabricate 3D CNS models are either difficult to pattern into complex structures due to their mechanical properties or lack appropriate bioinstructive cues. Here, we describe the functionalization of gelatin methacrylate (GelMA) with an N-cadherin extracellular peptide epitope to create a biomaterial termed GelMA-Cad. After photopolymerization, GelMA-Cad forms soft hydrogels that can maintain patterned architectures. The N-cadherin functionality promotes survival and maturation of iPSC-derived glutamatergic neurons into synaptically connected networks as determined by viral tracing and electrophysiology. Immunostaining reveals a pronounced increase in presynaptic and postsynaptic marker expression in GelMA-Cad relative to Matrigel, as well as extensive co-localization of these markers, thus highlighting the biological activity of the N-cadherin peptide. Overall, given its ability to enhance iPSC-derived neuron maturity and connectivity, GelMA-Cad should be broadly useful for in vitro studies of neural circuitry in health and disease.
Aneuploidy and deregulated DNA damage response define haploinsufficiency in breast tissues of BRCA2 mutation carriers
Authors: Karaayvaz Mihriban , Silberman Rebecca E , Langenbucher Adam , Saladi Srinivas Vinod , Ross Kenneth N , Zarcaro Elena , Desmond Andrea , Yildirim Murat , Vivekanandan Varunika , Ravichandran Hiranmayi , Mylavagnanam Ravindra , Specht Michelle C , Ramaswamy Sridhar , Lawrence Michael , Amon Angelika , Ellisen Leif W 
Published: August 2019

AbstractWomen harboring heterozygous germline mutations of BRCA2 have a 50-80% risk of developing breast cancer, yet the early pathogenesis of these cancers is poorly understood. We sought to reveal early steps in BRCA2-associated carcinogenesis through analysis of sorted cell populations from freshly-isolated, non-cancerous breast tissues among a cohort of BRCA2 mutation carriers and matched controls. Single-cell whole-genome sequencing demonstrates that >25% of BRCA2 carrier (BRCA2mut/+) luminal progenitor (LP) cells exhibit sub-chromosomal copy number variations (CNVs), which are rarely observed in non-carriers. Correspondingly, primary BRCA2mut/+ breast epithelia exhibit spontaneous and replication stress-induced DNA damage together with attenuated replication checkpoint and apoptotic responses, associated with an age-associated expansion of the LP compartment in human carrier tissues. These phenotypes are not associated with loss of wild-type BRCA2. Collectively, these findings provide evidence for BRCA2 haploinsufficiency and associated DNA damage in vivo that precede histologic abnormalities. These results provide unanticipated opportunities for new cancer risk assessment and prevention strategies in high-risk patients.
Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy
Authors: Horst Benjamin G. , Yokom Adam L. , Rosenberg Daniel J. , Morris Kyle L. , Hammel Michal , Hurley James H. , Marletta Michael A. 
Published: August 2019

AbstractSoluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-lengthManduca sextasGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO.
The microstructure investigation of plant architecture with X-ray microscopy
Authors: Zhang Wenting , Guo Tao , Chen Ke , La Ting , Bastians Philipp Alexander , Cao Chunjie 
Published: August 2019

ABSTRACTBackgroundIn recent years, the plant morphology has been well studied by multiple approaches at cellular and subcellular levels. Two-dimensional (2D) microscopy techniques offer imaging of plant structures on a wide range of magnifications for researchers. However, subcellular imaging is still challenging in plant tissues like roots and seeds.ResultsHere we use a three-dimensional (3D) imaging technology based on the ZEISS X-ray microscope (XRM) Versa and analyze several plant tissues from different plant species. The XRM provides new insights into plant structures using non-destructive imaging at high-resolution and high contrast. We also developed a workflow aiming to acquire accurate and high-quality images in the context of the whole specimen. Multiple plant samples including rice, tobacco, Arabidopsis and maize were used to display the differences of phenotypes, which indicates that the XRM is a powerful tool to investigate plant microstructure.ConclusionsOur work provides a novel observation method to evaluate and quantify tissue specific differences for a range of plant species. This new tool is suitable for non-destructive seed observation and screening.
Cell-scale biophysical determinants of cell competition in epithelia
Authors: Gradeci Daniel , Bove Anna , Vallardi Giulia , Lowe Alan R. , Banerjee Shiladitya , Charras Guillaume 
Published: August 2019

AbstractHow cells with different genetic makeups compete in tissues is an outstanding question in developmental biology and cancer research. Studies in recent years have revealed that cell competition can either be driven by short-range biochemical signalling or by long-range mechanical stresses in the tissue. To date, cell competition has generally been characterised at the population-scale, leaving the single-cell level mechanisms of competition elusive. Here, we use high time-resolution experimental data to construct a multi-scale agent-based model for epithelial cell competition, and use it to gain a conceptual understanding of the cellular factors that governs competition in cell populations within tissues. We find that a key determinant of mechanical competition is the difference in homeostatic density between winners and losers, while differences in growth rates and tissue organisation do not affect competition end-result. In contrast, the outcome and kinetics of biochemical competition is strongly influenced by local tissue organisation. Indeed, when loser cells are homogenously mixed with winners at the onset of competition, they are eradicated; however, when they are spatially separated, winner and loser cells coexist for long times. These findings suggest distinct biophysical origins for mechanical and biochemical modes of cell competition.
A neurophysiological study of noun-adjective agreement in Arabic: The impact of animacy and diglossia on the dynamics of language processing
Authors: Idrissi Ali , Mustafawi Eiman , Khwaileh Tariq , Muralikrishnan R. 
Published: August 2019

AbstractWe used event-related brain potentials to identify the neurophysiological responses of Arabic speakers to processing full and deflected agreement in plural noun-adjective constructions in Standard Arabic. Under full agreement, an adjective fully agrees in number and gender with a preceding plural noun, but only when this noun is human, while it is systematically marked feminine singular when the noun is non-human under deflected agreement. We recorded grammaticality judgment and ERP responses from 32 speakers of Arabic to sentences violating full and deflected agreement and their well-formed counterparts. The participants were relatively fast and accurate in judgingallthe sentences, although violations, especially deflected agreement violations, were not always deemed ungrammatical. However, the ERP responses show a differential processing of human versus non-human violations. Violations of full agreement involving human nouns elicited larger N400 and P600 components than violations of deflected agreement involving non-human nouns, whose ERP signatures were hardly distinguishable from those of their acceptable counterparts. Our results present evidence for animacy (more specifically, humanness) and inter-dialect effects on language processing. We argue that violations of Standard Arabic deflected agreement are not treated as outright violations because non-human referents permit both full and deflected agreement in Spoken Arabic. We discuss these results in light of the ERP literature on agreement processing and the role of animacy/humanness in grammar, and highlight the potential effect of diglossia on the architecture of the mental grammar of Arabic speakers.