bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular bundle sheath and mesophyll regulation of leaf water balance in response to chitin
Authors: Attia Ziv , Dalal Ahan , Moshelion Menachem 
Published: June 2018

ABSTRACTPlants can detect pathogen invasion by sensing pathogen-associated molecular patterns (PAMPs). This sensing process leads to the induction of defense responses. Most PAMP mechanisms of action have been described in the guard cells. Here, we describe the effects of chitin, a PAMP found in fungal cell walls, on the cellular osmotic water permeability (Pf) of the leaf vascular bundle-sheath (BS) and mesophyll cells and its subsequent effect on leaf hydraulic conductance (Kleaf).The BS is a parenchymatic tissue that tightly encases the vascular system. BS cells have been shown to controlKleafthrough changes in theirPf, for example, in response to ABA. It was recently reported that, in Arabidopsis, the chitin receptors chitin elicitor receptor kinase 1 (CERK1) and LYSINE MOTIF RECEPTOR KINASE 5 (LYK5) are highly expressed in the BS, as well as the neighboring mesophyll. Therefore, we studied the possible impact of chitin on these cells.Our results revealed that both BS cells and mesophyll cells exhibit a sharp decrease inPfin response to chitin treatment. In addition, xylem-fed chitin decreasedKleafand led to stomatal closure. However, anAtlyk5mutant showed none of these responses. ComplimentingAtLYK5specifically in the BS cells (using the SCARECROW promoter) and transient expresion in mesophyll cells each resulted in a response to chitin that was similar to that observed in the wild type. These results suggest that BS and mesophyll cells each play a role in the perception of apoplastic chitin and in initiating chitin-triggered immunity.Significance StatementPAMP perception by plant receptors triggers various defense responses important for plant immunity. Here we provide new insights into a topic that has received a great deal of previous attention, revealing that a chitin immune response is present in additional leaf tissues other than the stomata. Chitin perception by the bundle sheath cells enwrapping the whole leaf vascular system decrease its cellular osmotic permeability and leaf hydraulic conductance. This in turn, leads to hydraulic signals being sent to the stomata and regulates whole-leaf water balance in response to chitin application and, perhaps, during fungal infection. Emphasizing the dynamic role of the BS in chitin-sensing and water balance regulation.
Quantitation of single action potential-evoked Ca2+signals in CA1 pyramidal neuron presynaptic terminals
Authors: Church Emily , Hamid Edaeni , Alford Simon 
Published: June 2018

AbstractPresynaptic Ca2+evokes exocytosis, endocytosis, and short-term synaptic plasticity. However, Ca2+flux and interactions at presynaptic molecular targets are difficult to determine, because imaging has limited resolution. We measured single varicosity presynaptic Ca2+using Ca2+dyes as buffers, and constructed models of Ca2+dispersal. Action potentials evoked Ca2+transients (peak amplitude, 789±39 nM, within 2 ms of stimulation; decay times, 119±10 ms) with little variation when measured with low-affinity dye. Endogenous Ca2+buffering capacities, action potential-evoked free [Ca2+]¡ and total amounts entering terminals were determined using high-affinity Ca2+dyes to buffer Ca2+transients. These data constrained Monte Carlo (MCell) simulations of Ca2+entry, buffering, and removal. Data were well-fit with simulations of experimentally-determined Ca2+fluxes, buffered by simulated Calbindin28K. Simulations were consistent with clustered Ca2+entry followed within 2 ms by diffusion throughout the varicosity. Repetitive stimulation caused free varicosity Ca2+to sum. However, simulated in nanometer domains, its removal by pumps and buffering was negligible, while diffusion rates were high. Thus, Ca2+within tens of nanometers of entry, did not accumulate during sequential stimuli. A model of synaptotagmin1-Ca2+binding indicates that even with 10 μM free varicosity Ca2+, synaptogmin1 must be within tens of nanometers of channels to ensure occupation of all its Ca2+binding sites. Repetitive stimulation, which evokes short-term synaptic enhancement, does not modify probabilities of Ca2+fully occupying synaptotagmin1’s C2 domains, suggesting that enhancement is not mediated by Ca2+-synaptotagmin1. We conclude that at spatio-temporal scale of fusion machines, Ca2+necessary for their activation is diffusion dominated.
QstR-dependent regulation of natural competence and type VI secretion in Vibrio cholerae
Authors: Jaskólska Milena , Stutzmann Sandrine , Stoudmann Candice , Blokesch Melanie 
Published: June 2018

AbstractDuring growth on chitinous surfaces in its natural aquatic environment Vibrio cholerae develops natural competence for transformation and kills neighboring non-immune bacteria using a type VI secretion system (T6SS). Activation of these two phenotypes requires the chitin-induced regulator TfoX, but also integrates signals from quorum sensing via the intermediate regulator QstR, which belongs to the LuxR-type family of regulators. Here, we define the QstR regulon using RNA sequencing. Moreover, by mapping QstR binding sites using chromatin immunoprecipitation coupled with deep sequencing we demonstrate that QstR is likely a dual transcription factor that binds upstream of the up- and down-regulated genes. Like other LuxR-type family transcriptional regulators we show that QstR function is dependent on dimerization. However, in contrast to the well-studied LuxR-type biofilm regulator VpsT of V. cholerae, which requires the second messenger c-di-GMP, we show that QstR dimerization and function is c-di-GMP independent. Surprisingly, although ComEA, which is a periplasmic DNA-binding protein essential for transformation, is produced in a QstR-dependent manner, QstR-binding was not detected upstream of comEA suggesting the existence of a further regulatory pathway. Overall these results provide detailed insights into the function of a key regulator of natural competence and type VI secretion in V. cholerae.
Current and future goals are represented in opposite patterns in object-selective cortex
Authors: van Loon Anouk M. , Solis Katya Olmos , Fahrenfort Johannes J. , Olivers Christian N. L. 
Published: June 2018

AbstractAdaptive behavior requires the separation of current from future goals in working memory. We used fMRI of object-selective cortex to determine the representational (dis)similarities of memory representations serving current and prospective perceptual tasks. Participants remembered an object drawn from three possible categories as the target for one of two consecutive visual search tasks. A cue indicated whether the target object should be looked for first (currently relevant), second (prospectively relevant), or if it could be forgotten (irrelevant). Prior to the first search, representations of current, prospective and irrelevant objects were similar, with strongest decoding for current representations compared to prospective (Experiment 1) and irrelevant (Experiment 2). Remarkably, during the first search, prospective representations could also be decoded, but revealed anti-correlated voxel patterns compared to currently relevant representations of the same category. We propose that the brain separates current from prospective memories within the same neuronal ensembles through opposite representational patterns.
Thrombocyte inhibition restores protective immunity to mycobacterial infection in zebrafish
Authors: Hortle Elinor , Johnson Khelsey E. , Johansen Matt D. , Nguyen Tuong , Shavit Jordan A. , Britton Warwick J. , Tobin David M. , Oehlers Stefan H. 
Published: June 2018

AbstractInfection-induced thrombocytosis is a clinically important complication of tuberculosis (TB). Recent studies have separately highlighted a correlation of platelet activation with TB severity and utility of aspirin as a host-directed therapy for TB that modulates the inflammatory response. Here we investigate the possibility that the beneficial effects of aspirin are related to an anti-platelet mode of action. We utilize the zebrafish-Mycobacterium marinum model to show mycobacteria drive host hemostasis through the formation of granulomas. Treatment of infected zebrafish with aspirin or platelet-specific glycoprotein IIb/IIIa inhibitors reduced mycobacterial burden demonstrating a detrimental role for infection-induced thrombocyte activation. We found platelet inhibition reduced thrombocyte-macrophage interactions and restored indices of macrophage-mediated immunity to mycobacterial infection. Pathological thrombocyte activation and granuloma formation were found to be intrinsically linked illustrating a bidirectional relationship between host hemostasis and TB pathogenesis. Our study illuminates platelet activation as an efficacious target of anti-platelets drugs including aspirin, a widely available and affordable host-directed therapy candidate for tuberculosis.Key PointsInhibition of thrombocyte activation improves control of mycobacterial infection.Inhibition of thrombocyte activation reduces thrombocyte-macrophage interactions and improves indices of macrophage immune function against mycobacterial infection.
Precise prediction of antibiotic resistance in Escherichia coli from full genome sequences
Authors: Moradigaravand Danesh , Palm Martin , Farewell Anne , Mustonen Ville , Warringer Jonas , Parts Leopold 
Published: June 2018

AbstractThe emergence of microbial antibiotic resistance is a global health threat. In clinical settings, the key to controlling spread of resistant strains is accurate and rapid detection. As traditional culture-based methods are time consuming, genetic approaches have recently been developed for this task. The diagnosis is typically made by measuring a few known determinants previously identified from whole genome sequencing, and thus is restricted to existing information on biological mechanisms. To overcome this limitation, we employed machine learning models to predict resistance to 11 compounds across four classes of antibiotics from existing and novel whole genome sequences of 1936 E. coli strains. We considered a range of methods, and examined population structure, isolation year, gene content, and polymorphism information as predictors. Gradient boosted decision trees consistently outperformed alternative models with an average F1 score of 0.88 on held-out data (range 0.66-0.96). While the best models most frequently employed all inputs, an average F1 score of 0.73 could be obtained using population structure information alone. Single nucleotide variation data were less useful, and failed to improve prediction for ten out of 11 antibiotics. These results demonstrate that antibiotic resistance in E. coli can be accurately predicted from whole genome sequences without a priori knowledge of mechanisms, and that both genomic and epidemiological data are informative. This paves way to integrating machine learning approaches into diagnostic tools in the clinic.SummaryOne of the major health threats of 21st century is emergence of antibiotic resistance. To manage its economic impact, efforts are made to develop novel diagnostic tools that rapidly detect resistant strains in clinical settings. In our study, we employed a range machine learning tools to predict antibiotic resistance from whole genome sequencing data for E. coli. We used the presence or absence of genes, population structure and isolation year of isolates as predictors, and could attain average precision of 0.93 and recall of 0.83, without prior knowledge about the causal mechanisms. These results demonstrate the potential application of machine learning methods as a diagnostic tool in healthcare settings.
A comparative genome analysis of Rift Valley Fever virus isolates from foci of the disease outbreak in South Africa in 2008-2010
Authors: Maluleke Moabi R. , Phosiwa Maanda , Schalkwyk Antoinette van , Michuki George , Lubisi Baratang A. , Kegakilwe Phemelo S. , Kemp Steve J. , Majiwa Phelix A.O. 
Published: June 2018

AbstractRift Valley fever (RVF) is a re-emerging zoonotic disease responsible for major losses in livestock production, with negative impact on the livelihoods of both commercial and resource-poor farmers in sub-Sahara African countries. The disease remains a threat in countries where its mosquito vectors thrives. Outbreaks of RVF usually follow weather conditions which favour increase in mosquito populations. Such outbreaks are usually cyclical, occurring every 10-15 years.Recent outbreaks of the disease in South Africa have occurred unpredictably and with increased frequency. In 2008 outbreaks were reported in Mpumalanga, Limpopo and Gauteng provinces, followed by a 2009 outbreak in KwaZulu-Natal, Mpumalanga and Northern Cape provinces and in 2010 in the Eastern Cape, Northern Cape, Western Cape, North West, Free State and Mpumalanga provinces. By August 2010, 232 confirmed infections had been reported in humans, with 26 confirmed deaths.To investigate the evolutionary dynamics of RVF viruses (RVFVs) circulating in South Africa, we undertook complete genome sequence analysis of isolates from animals at discrete foci of the 2008-2010 outbreaks. The genome sequences of these viruses were compared with viruses from earlier outbreaks in South Africa and in other countries. The data indicates that one 2009 and all the 2008 isolates from South Africa and Madagascar (M49/08) cluster in Lineage C or Kenya-1. The remaining of the 2009 and 2010 isolates cluster within Lineage H, except isolate M259_RSA_09, a probable segment M reassortant.Author summaryA single RVF virus serotype exists, yet differences in virulence and pathogenicity of the virus have been observed. This necessitates the need for detailed genetic characterization of various isolates of the virus. The RVF virus isolates that caused the 2008-2010 disease outbreaks in South Africa were most probably reassortants. Reassortment results from exchange of portions of the genome, particularly those of segment M. Although clear association between RVFV genotype and phenotype has not been established, various amino acid substitutions have been implicated in the phenotype. Viruses with amino acid substitutions from glycine to glutamic acid at position 277 of segment M have been shown to be more virulent in mice in comparison to viruses with glycine at the same position. Phylogenetic analysis indicated the viruses responsible for the 2008-2010 RVF outbreaks in South Africa were not introduced from outside the country, but mutated in time and caused the outbreaks when environmental conditions became favourable.
The BTB-ZF transcription factor Tramtrack69 shapes neural cell lineages by coordinating cell proliferation and cell fate
Authors: Simon Françoise , Ramat Anne , Louvet-Vallée Sophie , Lacoste Jérôme , Burg Angélique , Audibert Agnès , Gho Michel 
Published: June 2018

AbstractCell diversity in multicellular organisms relies on coordination between cell proliferation and the acquisition of cell identity. The equilibrium between these two processes is essential to assure the correct number of determined cells at a given time at a given place. Here, we show that Tramtrack-69 (Ttk69, a BTB-ZF transcription factor ortholog of the human PLZF factor) plays an essential role in controlling this balance. In theDrosophilabristle cell lineage, producing the external sensory organs composed by a neuron and accessory cells, we show thatttk69loss of function leads to supplementary neural-type cells at the expense of accessory cells. Our data indicate that Ttk69 (1) promotes cell-cycle exit of newborn terminal cells by downregulatingcycE, the principal cyclin involved in S-phase entry and (2) regulates cell fate acquisition and terminal differentiation by downregulating the expression ofhamletand upregulating that ofSuppressor of Hairless, two transcription factors involved in neural-fate acquisition and accessory-cell differentiation, respectively. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate commitment.Summary statementTramtrack-69, a transcription factor orthologous to the human tumor-suppressor PLZF, plays a central role in precursor cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate determination.
ATRAIDregulates the action of nitrogen-containing bisphosphonates on bone
Authors: Surface Lauren E. , Burrow Damon T. , Li Jinmei , Park Jiwoong , Kumar Sandeep , Lyu Cheng , Song Niki , Yu Zhou , Rajagopal Abbhirami , Bae Yangjin , Lee Brendan H. , Mumm Steven , Gu Charles C. , Baker Jonathan C. , Mohseni Mahshid , Sum Melissa , Huskey Margaret , Duan Shenghui , Bijanki Vinieth N. , Civitelli Roberto , Gardner Michael J. , McAndrew Chris M. , Ricci William M. , Gurnett Christina A. , Diemer Kathryn , Wan Fei , Costantino Christina L. , Shannon Kristen M. , Raje Noopur , Dodson Thomas B. , Haber Daniel A. , Carette Jan E. , Varadarajan Malini , Brummelkamp Thijn R. , Birsoy Kivanc , Sabatini David M. , Haller Gabe , Peterson Timothy R. 
Published: June 2018

AbstractNitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFFs) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase (FDPS), resulting in defects in protein prenylation. Yet it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene,ATRAID. Loss ofATRAIDfunction results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation.ATRAIDis required for alendronate inhibition of osteoclast function, andATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Lastly, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF.ATRAIDis one of three genes that contain rare non-synonymous coding variants in patients with ONJ or AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation inATRAIDas conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.One Sentence SummaryATRAIDis essential for responses to the commonly prescribed osteoporosis drugs nitrogen-containing bisphosphonates.OverlineBONE
Actin-inspired feedback couples speed and persistence in a Cellular Potts Model of cell migration
Authors: Wortel Inge M. N. , Niculescu Ioana , Kolijn P. Martijn , Gov Nir , de Boer Rob J. , Textor Johannes 
Published: June 2018

ABSTRACTCell migration is astoundingly diverse. Molecular signatures, cell-cell and cell-matrix interactions, and environmental structures each play their part in shaping cell motion, yielding numerous different cell morphologies and migration modes. Nevertheless, in recent years, a simple unifying law was found to describe cell migration across many different cell types and contexts: faster cells turn less frequently. Given this universal coupling between speed and persistence (UCSP), from a modelling perspective it is important to know whether computational models of cell migration capture this speed-persistence link. Here, we present an in-depth characterisation of an existing Cellular Potts Model (CPM). We first show that this model robustly reproduces the UCSP without having been designed for this task. Instead, we show that this fundamental law of migration emerges spontaneously through a crosstalk of intracellular mechanisms, cell shape, and environmental constraints, resembling the dynamic nature of cell migrationin vivo. Our model also reveals how cell shape dynamics can further constrain cell motility by limiting both the speed and persistence a cell can reach, and how a rigid environment such as the skin can restrict cell motility even further. Our results further validate the CPM as a model of cell migration, and shed new light on the speed-persistence coupling that has emerged as a fundamental property of migrating cells.SIGNIFICANCEThe universal coupling between speed and persistence (UCSP) is the first general quantitative law describing motility patterns across the versatile spectrum of migrating cells. Here, we show – for the first time – that this migration law emerges spontaneously in an existing, highly popular computational model of cell migration. Studying the UCSP in entirely different model frameworks,notexplicitly built with this law in mind, can help uncover how intracellular dynamics, cell shape, and environment interact to produce the diverse motility patterns observed in migrating cells.
Reduced transfer of visuomotor adaptation is associated with aberrant sense of agency in Schizophrenia
Authors: Bansal Sonia , Murthy Karthik G , Fitzgerald Justin , Schwartz Barbara L. , Joiner Wilsaan M. 
Published: June 2018

ABSTRACTOne deficit associated with schizophrenia (SZ) is the reduced ability to distinguish sensations resulting from self-caused actions from those due to external sources. This reduced sense of agency (SoA, awareness of ownership over self-generated actions) is hypothesized to result from a diminished utilization of internal monitoring signals of self-movement (i.e., efferent copy) which subsequently impairs forming and utilizing sensory prediction errors (differences between the predicted and actual sensory consequences resulting from movement). Here, we investigated the connections between clinical SZ symptoms and motor adaptation, a process that uses sensory prediction errors to update motor output. Schizophrenia patients (SZP, N=30) and non-psychiatric healthy control subjects (HC, N=31) adapted to altered movement visual feedback, and then applied the motor recalibration to untested contexts (i.e., the spatial generalization to untrained targets). Although adaptation was similar for SZP and controls, the extent of generalization was significantly less for SZP; movement trajectories made by patients to the furthest untrained target (135°) before and after adaptation were largely indistinguishable. Interestingly, deficits in the generalization were correlated to positive symptoms of psychosis (e.g., hallucinations), but not negative symptoms. Generalization was also associated with subjective measures of SoA across both SZP and HC, emphasizing the major role action awareness plays in motor behavior, and suggesting that tendencies to misattribute agency, even in HC, manifest in abnormal motor performance. We discuss the possible link of these findings to cerebellar circuit abnormalities that may be a common source for deficits in the utilization of sensory prediction errors and aberrant SoA.