bluuebunny/crossref_metadata_2025_split huggingface dataset:
A membrane-depolarizing toxin substrate of theStaphylococcus aureusType VII secretion system mediates intra-species competition
Authors: Ulhuq Fatima R. , Gomes Margarida C. , Duggan Gina , Guo Manman , Mendonca Chriselle , Buchanan Grant , Chalmers James D. , Cao Zhenping , Kneuper Holger , Murdoch Sarah , Thomson Sarah , Strahl Henrik , Trost Matthias , Mostowy Serge , Palmer Tracy 
Published: October 2018

AbstractThe type VII protein secretion system (T7SS) is conserved acrossStaphylococcus aureusstrains and plays important roles in virulence and interbacterial competition. To date only one T7SS substrate protein, encoded in a subset ofS. aureusgenomes, has been functionally characterized. Here, using an unbiased proteomic approach, we identify TspA as a further T7SS substrate. TspA is encoded distantly from the T7SS gene cluster and is found across allS. aureusstrains as well as inListeriaand Enterococci. Heterologous expression of TspA fromS. aureusstrain RN6390 indicates its C-terminal domain is toxic when targeted to theEscherichia coliperiplasm and that it depolarizes the cytoplasmic membrane. The membrane depolarizing activity is alleviated by co-production of the membrane-bound TsaI immunity protein, which is encoded adjacent totspAon theS. aureuschromosome. Using a zebrafish hindbrain ventricle infection model, we demonstrate that the T7SS of strain RN6390 promotes bacterial replicationin vivo, and deletion oftspAleads to increased bacterial clearance. The toxin domain of TspA is highly polymorphic andS. aureusstrains encode multipletsaIhomologues at thetspAlocus, suggestive of additional roles in intra-species competition. In agreement, we demonstrate TspA-dependent growth inhibition of RN6390 by strain COL in the zebrafish infection model that is alleviated by the presence of TsaI homologues.Significance statementStaphylococcus aureus, a human commensal organism that asymptomatically colonizes the nares, is capable of causing serious disease following breach of the mucosal barrier.S. aureusstrains encode a Type VII secretion system (T7SS) that is required for virulence in mouse infection models, and some strains also secrete a nuclease toxin by this route that has antibacterial activity. Here we identify TspA, widely found in Staphylococci and other pathogenic bacteria, as a T7 substrate. We show that TspA has membrane-depolarizing activity and thatS. aureususes TspA to inhibit the growth of a bacterial competitorin vivo.
Bumetanide prevents brain trauma-induced depressive-like behavior
Authors: Emmanuelle Goubert , Marc Altvater , Marie-Noelle Rovira , Ilgam Khalilov , Morgane Mazzarino , Anne Sebastiani , Michael Schaefer , Claudio Rivera , Christophe Pellegrino 
Published: October 2018

AbstractBrain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.
Effect of light intensity and nutritional value of food resources on flight response of adult parasitoid, Cotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae)
Authors: Kapinder  , Tarkeshwar  , Singh Ashok Kumar 
Published: October 2018

AbstractCotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae) is the major larval parasitoid of Plutella xylostella (L) (Lepidoptera: Plutellidae), which is a serious pest of cruciferous plants throughout the world. We evaluated the influence of light intensities and feeding conditions on the vertical angle of flight in freshly emerged wasps in a cylinder having diameter 15cm and height 30cm. Light intensity was found to directly affects the flight activity. Increase in light intensity causes increase in vertical flight of the female wasps. However, Increase in light intensity did not influence the inclination of vertical flight in males. Feeding condition was also found to affect the vertical flight of the wasps. Honey odour, from below the flight chamber, arrested the flight of unfed or sucrose fed wasps. However, flight of honey fed wasps was not affected by honey odour. Male flight response was also influenced by feeding condition and light intensity but the response was not as higher as shown by females. The present study is useful for selecting suitable food prior to inundative release of parasitoid in the field at suitable time period of the day.
Human neurons from Christianson syndrome iPSCs reveal allele-specific responses to rescue strategies
Authors: Lizarraga Sofia B. , Maguire Abbie M. , Ma Li , van Dyck Laura I. , Wu Qing , Nagda Dipal , Livi Liane L. , Pescosolido Matthew F. , Schmidt Michael , Alabi Shanique , Cowen Mara H. , Brito-Vargas Paul , Hoffman-Kim Diane , Gamsiz Uzun Ece D. , Schlessinger Avner , Jones Richard N. , Morrow Eric M. 
Published: October 2018

AbstractHuman genetic disorders provide a powerful lens to understanding the human brain. Induced pluripotent stem cells (iPSC) represent an important, new resource for mechanistic studies and therapeutic development. Christianson syndrome (CS), an X-linked neurological disorder with attenuation of brain growth postnatally (postnatal microcephaly), is caused by mutations in SLC9A6, the gene encoding endosomal Na+/H+ exchanger 6 (NHE6). We developed CS iPSC lines from patients with a mutational spectrum, as well as robust biologically-related and isogenic controls. We demonstrate that mutations in CS lead to loss of protein function by a variety of mechanisms. Regardless of mutation, all patient-derived neurons demonstrate reduced neurite growth and arborization, likely underlying diminished postnatal brain growth in patients. Additionally, phenotype rescue strategies show allele-specific responses: a gene replacement strategy shows efficacy in nonsense mutations but not in a missense mutation, whereas application of exogenous trophic factors (BDNF or IGF-1) rescues arborization phenotypes across all mutations. Our data emphasize the important principle of personalized medicine whereby success of some therapeutic strategies may be more linked to patient genotype than others.
Electron Microscopy Analysis of hAPP-Induced Neurodegeneration in the Glomerular Network
Authors: Robbins Anastasia E. , Lehmann Katherine S. , Bai Li , Belluscio Leonardo 
Published: October 2018

AbstractLoss of smell is an early indicator of Alzheimer’s disease (AD), making the olfactory system an accessible model to study the effect of AD related proteins such as Amyloid Precursor Protein (APP). The regenerative capacity of the system further enables studies of circuit recovery after APP-induced degeneration. While the cellular effects of APP are well documented, little is known about its effects on brain circuits at the ultrastructural level. To study circuitry changes, we overexpressed humanized APP with familial AD mutations (hAPP) in olfactory sensory neurons and performed serial electron microscopy on olfactory bulb glomeruli from both control and hAPP expressing mice. We found that hAPP-expressing mice showed a striking decrease in glomerular connectivity along with widespread changes of subcellular structures. By then turning off hAPP expression for 6 weeks we tested the capacity of glomerular circuits to recover and found clear restoration of both connectivity and subcellular features, including an increase in post-synaptic density to above the control level. These data provide an important ultrastructural view of olfactory regions associated with AD and suggest that circuit recovery is possible in brain tissue that has experienced APP-induced neurodegeneration.
Maximum Caliber can build and infer models of oscillation in a three-gene feedback network
Authors: Firman Taylor , Amgalan Anar , Ghosh Kingshuk 
Published: October 2018

AbstractSingle-cell protein expression time trajectories provide rich temporal data quantifying cellular variability and its role in dictating fitness. However, theoretical models to analyze and fully extract information from these measurements remain limited for three reasons: i) gene expression profiles are noisy, rendering models of averages inapplicable, ii) experiments typically measure only a few protein species while leaving other molecular actors – necessary to build traditional bottom-up models – unnoticed, and iii) measured data is in fluorescence, not particle number. We have recently addressed these challenges in an alternate top-down approach using the principle of Maximum Caliber (MaxCal) to model genetic switches with one and two protein species. In the present work we address scalability and broader applicability of MaxCal by extending to a three-gene (A, B, C) feedback network that exhibits oscillation, commonly known as the repressilator. We test MaxCal’s inferential power by using synthetic data of noisy protein number time traces – serving as a proxy for experimental data – generated from a known underlying model. We notice that the minimal MaxCal model – accounting for production, degradation, and only one type of symmetric coupling between all three species – reasonably infers several underlying features of the circuit such as the effective production rate, degradation rate, frequency of oscillation, and protein number distribution. Next, we build models of higher complexity including different levels of coupling between A, B, and C and rigorously assess their relative performance. While the minimal model (with four parameters) performs remarkably well, we note that the most complex model (with six parameters) allowing all possible forms of crosstalk between A, B, and C slightly improves prediction of rates, but avoids ad-hoc assumption of all the other models. It is also the model of choice based on Bayesian Information Criteria. We further analyzed time trajectories in arbitrary fluorescence (using synthetic trajectories) to mimic realistic data. We conclude that even with a three-protein system including both fluorescence noise and intrinsic gene expression fluctuations, MaxCal can faithfully infer underlying details of the network, opening up future directions to model other network motifs with many species.
High resolution atlas of the venous brain vasculature from 7 T quantitative susceptibility maps
Authors: Huck Julia , Wanner Yvonne , Fan Audrey P. , Jäger Anna-Thekla , Grahl Sophia , Schneider Uta , Villringer Arno , Steele Christopher J. , Tardif Christine L. , Bazin Pierre-Louis , Gauthier Claudine J. 
Published: October 2018

AbstractThe vascular organization of the human brain can determine neurological and neurophysiological functions, yet thus far it has not been comprehensively mapped. Aging and diseases such as dementia are known to be associated with changes to the vasculature and normative data could help detect these vascular changes in neuroimaging studies. Furthermore, given the well-known impact of venous vessels on the blood oxygen level dependent (BOLD) signal, information about the common location of veins could help detect biases in existing datasets. In this work, a quantitative atlas of the venous vasculature using quantitative susceptibility maps (QSM) acquired with a 0.6 mm isotropic resolution is presented. The Venous Neuroanatomy (VENAT) atlas was created from 5 repeated 7 Tesla MRI measurements in young and healthy volunteers (n = 20, 10 females, mean age = 25.1 ± 2.5 years) using a two-step registration method on 3D segmentations of the venous vasculature. This cerebral vein atlas includes the average vessel location, diameter (mean: 0.84 ± 0.33 mm) and curvature (0.11 ± 0.05 mm−1) from all participants and provides an in vivo measure of the angio-architectonic organization of the human brain and its variability. This atlas can be used as a basis to understand changes in the vasculature during aging and neurodegeneration, as well as vascular and physiological effects in neuroimaging.
Actomyosin-mediated nanostructural remodeling of the presynaptic vesicle pool by cannabinoids induces long-term depression
Authors: McFadden Maureen H. , Xu Hao , Cui Yihui , Piskorowski Rebecca A. , Leterrier Christophe , Zala Diana , Venance Laurent , Chevaleyre Vivien , Lenkei Zsolt 
Published: October 2018

AbstractEndo- and exocannabinoids, such as the psychoactive component of marijuana, exert their effects on brain function by inducing several forms of synaptic plasticity through the modulation of presynaptic vesicle release1-3. However, the molecular mechanisms underlying the widely expressed endocannabinoid-mediated long-term depression3 (eCB-LTD), are poorly understood. Here, we reveal that eCB-LTD depends on the contractile properties of the pre-synaptic actomyosin cytoskeleton. Preventing this contractility, both directly by inhibiting non-muscle myosin II NMII ATPase and indirectly by inhibiting the upstream Rho-associated kinase ROCK, abolished long-term, but not short-term forms of cannabinoid-induced functional plasticity in both inhibitory hippocampal and excitatory cortico-striatal synapses. Furthermore, using 3D superresolution microscopy, we find an actomyosin contractility-dependent redistribution of synaptic vesicle pools within the presynaptic compartment following cannabinoid receptor activation, leading to vesicle clustering and depletion from the pre-synaptic active zone. These results suggest that cannabinoid-induced functional plasticity is mediated by a nanoscale structural reorganization of the presynaptic compartment produced by actomyosin contraction. By introducing the contractile NMII as an important actin binding/structuring protein in the dynamic regulation of synaptic function, our results open new perspectives in the understanding of mechanisms of synaptic and cognitive function, marijuana intoxication and psychiatric pathogenesis.
Reduced visual and frontal cortex activation during visual working memory in grapheme-colour synaesthetes relative to young and older adults
Authors: Pfeifer Gaby , Ward Jamie , Sigala Natasha 
Published: October 2018

AbstractThe sensory recruitment model envisages visual working memory (VWM) as an emergent property that is encoded and maintained in sensory (visual) regions. The model implies that enhanced sensory-perceptual functions, as in synaesthesia, entail a dedicated VWM-system, showing reduced visual cortex activity as a result of neural specificity. By contrast, sensory-perceptual decline, as in old age, is expected to show enhanced visual cortex activity as a result of neural broadening. To test this model, young grapheme-colour synaesthetes, older adults and young controls engaged in a delayed pair-associative retrieval and a delayed matching-to-sample task, consisting of achromatic fractal stimuli that do not induce synaesthesia. While a previous analysis of this dataset (Pfeifer et al., 2016) has focused on cued retrieval and recognition of pair-associates (i.e. long-term memory), the current study focuses on visual working memory and considers, for the first time, the crucial delay period in which no visual stimuli are present, but working memory processes are engaged. Participants were trained to criterion and demonstrated comparable behavioural performance on VWM tasks. Whole-brain and region-of-interest-analyses revealed significantly lower activity in synaesthetes’ middle frontal gyrus and visual regions (cuneus, inferior temporal cortex) respectively, suggesting greater neural efficiency relative to young and older adults in both tasks. The results support the sensory recruitment model and can explain age and individual WM-differences based on neural specificity in visual cortex.
Two-component systems regulate swarming inPseudomonas aeruginosaPA14
Authors: Joge Shubham , Kollaran Ameen M. , Kotian Harshitha S. , Badal Divakar , Prakash Deep , Mishra Ayushi , Varma Manoj , Singh Varsha 
Published: October 2018

ABSTRACTSwarming inPseudomonas aeruginosais a quorum-dependant motility over semi-solid surfaces. On soft agar,P. aeruginosaexhibits a dendritic swarm pattern, with multiple levels of branching. Swarm patterns vary considerably depending upon the experimental design. In the present study, we show that the swarm pattern is plastic and media dependent. We define several quantifiable, macroscale features of the swarm to study the plasticity observed across media. Further, through a targeted screen of 113 genes encoding two-component system (TCS) components, we show that 44 TCS genes regulate PA14 swarming in a contextual fashion. However, only four TCS genes are essential for swarming. Many swarming-defective TCS mutants are highly efficient in biofilm formation indicating an antagonistic relationship between swarming and biofilm states inP. aeruginosa.
ChiCMaxima: a robust and simple pipeline for detection and visualization of chromatin looping in Capture Hi-C
Authors: Ben Zouari Yousra , Molitor Anne M , Sikorska Natalia , Pancaldi Vera , Sexton Tom 
Published: October 2018

AbstractCapture Hi-C (CHi-C) is a new technique for assessing genome organization, based on chromosome conformation capture coupled to oligonucleotide capture of regions of interest such as gene promoters. Chromatin loop detection is challenging, since existing Hi-C/4C-like analyses, which make different assumptions about the technical biases presented, are often unsuitable. We describe a new approach, ChiCMaxima, which uses local maxima combined with a background model to detect DNA looping interactions, integrating information from biological replicates. ChiCMaxima shows more stringency and robustness compared to previously developed tools. The tool includes a GUI browser for flexible visualization of CHi-C profiles alongside epigenomic tracks.
Substantial Batch Effects in TCGA Exome Sequences Undermine Pan-Cancer Analysis of Germline Variants
Authors: Rasnic Roni , Brandes Nadav , Zuk Or , Linial Michal 
Published: October 2018

ABSTRACTBackgroundIn recent years, research on cancer predisposition germline variants has emerged as a prominent field. The identity of somatic mutations is based on a reliable mapping of the patient germline variants. In addition, the statistics of germline variants frequencies in healthy individuals and cancer patients is the basis for seeking candidates for cancer predisposition genes. The Cancer Genome Atlas (TCGA) is one of the main sources of such data, providing a diverse collection of molecular data including deep sequencing for more than 30 types of cancer from >10,000 patients.MethodsOur hypothesis in this study is that whole exome sequences from healthy blood samples of cancer patients are not expected to show systematic differences among cancer types. To test this hypothesis, we analyzed common and rare germline variants across six cancer types, covering 2,241 samples from TCGA. In our analysis we accounted for inherent variables in the data including the different variant calling protocols, sequencing platforms, and ethnicity.ResultsWe report on substantial batch effects in germline variants associated with cancer types. We attribute the effect to the specific sequencing centers that produced the data. Specifically, we measured 30% variability in the number of reported germline variants per sample across sequencing centers. The batch effect is further expressed in nucleotide composition and variant frequencies. Importantly, the batch effect causes substantial differences in germline variant distribution patterns across numerous genes, including prominent cancer predisposition genes such as BRCA1, RET, MAX, and KRAS. For most of known cancer predisposition genes, we found a distinct batch-dependent difference in germline variants.ConclusionTCGA germline data is exposed to strong batch effects with substantial variabilities among TCGA sequencing centers. We claim that those batch effects are consequential for numerous TCGA pan-cancer studies. In particular, these effects may compromise the reliability and the potency to detect new cancer predisposition genes. Furthermore, interpretation of pan-cancer analyses should be revisited in view of the source of the genomic data after accounting for the reported batch effects.
Evolutionary stasis of the pseudoautosomal boundary in strepsirrhine primates
Authors: Shearn Rylan , Wright Alison E. , Mousset Sylvain , Régis Corinne , Penel Simon , Lemaitre Jean-François , Douay Guillaume , Crouau-Roy Brigitte , Lecompte Emilie , Marais Gabriel A.B. 
Published: October 2018

AbstractSex chromosomes are typically comprised of a non-recombining region and a recombining pseudoautosomal region. Accurately quantifying the relative size of these regions is critical for sex chromosome biology both from a functional (i.e. number of sex-linked genes) and evolutionary perspective (i.e. extent of Y degeneration and X-Y heteromorphy). The evolution of the pseudoautosomal boundary (PAB) - the limit between the recombining and the non-recombining regions of the sex chromosomes - is well documented in haplorrhines (apes and monkeys) but not in strepsirrhines (lemurs and lorises), which represent almost 30% of all primates. Here we studied the PAB of seven species representing the main strepsirrhine lineages by sequencing a male and a female genome in each species and using sex differences in coverage to identify the PAB. We found that during primate evolution, the PAB has remained unchanged in strepsirrhines whereas several recombination suppression events moved the PAB and shortened the pseudoautosomal region in haplorrhines. Strepsirrhines are well known to have much lower sexual dimorphism than haplorrhines. We suggest that mutations with antagonistic effects between males and females have driven recombination suppression and PAB evolution in haplorrhines. Our work supports the view that sexually antagonistic mutations have influenced the evolution of sex chromosomes in primates.