bluuebunny/crossref_metadata_2025_split huggingface dataset:
TorsinB overexpression prevents abnormal twisting in DYT1 dystonia mouse models
Authors: Li Jay , Liang Chun-Chi , Pappas Samuel S. , Dauer William T. 
Published: November 2019

AbstractGenetic redundancy can be exploited to identify therapeutic targets for inherited disorders. An example is DYT1 dystonia, a neurodevelopmental movement disorder caused by a loss-of-function (LOF) mutation in theTOR1Agene encoding torsinA. Prior work demonstrates that torsinA and its paralog torsinB have conserved functions at the nuclear envelope. This work established that low neuronal levels of torsinB dictate the neuronal selective phenotype of nuclear membrane budding. Here, we examined whether torsinB expression levels impact the onset or severity of abnormal movements, or neuropathological features in DYT1 mouse models. We demonstrate that torsinB levels bidirectionally regulate these phenotypes. Reducing torsinB levels causes a dosedependent worsening whereas torsinB overexpression rescues torsinA LOF-mediated abnormal movements and neurodegeneration. These findings identify torsinB as a potent modifier of torsinA LOF phenotypes and suggest that augmentation of torsinB expression level may retard or prevent symptom development in DYT1 dystonia.
A Graph Auto-Encoder for Haplotype Assembly and Viral Quasispecies Reconstruction
Authors: Ke Ziqi , Vikalo Haris 
Published: November 2019

AbstractReconstructing components of a genomic mixture from data obtained by means of DNA sequencing is a challenging problem encountered in a variety of applications including single individual haplotyping and studies of viral communities. High-throughput DNA sequencing platforms oversample mixture components to provide massive amounts of reads whose relative positions can be determined by mapping the reads to a known reference genome; assembly of the components, however, requires discovery of the reads’ origin – an NP-hard problem that the existing methods struggle to solve with the required level of accuracy. In this paper, we present a learning framework based on a graph auto-encoder designed to exploit structural properties of sequencing data. The algorithm is a neural network which essentially trains to ignore sequencing errors and infers the posterior probabilities of the origin of sequencing reads. Mixture components are then reconstructed by finding consensus of the reads determined to originate from the same genomic component. Results on realistic synthetic as well as experimental data demonstrate that the proposed framework reliably assembles haplotypes and reconstructs viral communities, often significantly outperforming state-of-the-art techniques. Source codes and datasets are publicly available athttps://github.com/WuLoli/GAEseq.
Decoding the multimorbidities among psychiatric disorders and cognitive functioning
Authors: Golovina E. , Vickers M.H. , Erb C.D. , O’Sullivan J.M. 
Published: November 2019

AbstractThe regulatory contribution that single-nucleotide polymorphisms (SNPs) associated with psychiatric and cognitive phenotypes make to multimorbidity is unknown. Here, we integrate 3D genome organization and expression quantitative trait (eQTL) analyses to identify the genes and biological pathways that are functionally impacted by 2,893 GWAS SNPs associated with cognitive functioning and five psychiatric disorders (i.e. attention deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder (BD), unipolar depression (UD) and schizophrenia (SCZ)). The analysis revealed 33 genes and 62 pathways that were commonly affected by the gene regulatory interactions associated with all six phenotypes despite there being no common SNPs and eQTLs. 38 ADHD-, 78 anxiety-, 81 BD-, 169 UD-, 225 SCZ- and 185 cognition-associated genes represent known drug targets. Four genes were affected by eQTLs from all six phenotypes. Collectively, our results represent the foundation for a shift from a gene-targeted towards a pathway-based approach to the treatment of multimorbid conditions.
A novel pathway linking plasma membrane and chloroplasts is co-opted by pathogens to suppress salicylic acid-dependent defences
Authors: Medina-Puche Laura , Tan Huang , Dogra Vivek , Wu Mengshi , Rosas-Diaz Tabata , Wang Liping , Ding Xue , Zhang Dan , Fu Xing , Kim Chanhong , Lozano-Duran Rosa 
Published: November 2019

SUMMARYChloroplasts are crucial players in the activation of defensive hormonal responses during plant-pathogen interactions. Here, we show that a plant virus-encoded protein re-localizes from the plasma membrane to chloroplasts upon triggering plant defence, interfering with the chloroplast-dependent activation of anti-viral salicylic acid (SA) biosynthesis. Strikingly, we have found that plant pathogens from different kingdoms seem to have convergently evolved to target chloroplasts and impair SA-dependent defences following an association with membranes, which is based on the co-existence of two subcellular targeting signals, an N-myristoylation site and a chloroplast transit peptide. This pattern is also present in plant proteins, at least one of which conversely activates SA defences from the chloroplast. Taken together, our results suggest that a pathway linking plasma membrane to chloroplasts and activating defence exists in plants, and that such pathway has been co-opted by plant pathogens during host-pathogen co-evolution to promote virulence through suppression of SA responses.
Dispersal patterns of Trypanosoma cruzi in Arequipa, Peru
Authors: Berry Alexander S.F. , Salazar-Sánchez Renzo , Castillo-Neyra Ricardo , Borrini-Mayorí Katty , Arevalo-Nieto Claudia , Chipana-Ramos Claudia , Vargas-Maquera Melina , Ancca-Juarez Jenny , Náquira-Velarde César , Levy Michael Z. , Brisson Dustin 
Published: November 2019

AbstractAnthropogenic environmental alterations such as urbanization can threaten native populations as well as create novel environments that allow human pests and pathogens to thrive. As the number and size of urban environments increase globally, it is more important than ever to understand the dispersal dynamics of hosts, vectors and pathogens of zoonotic disease systems. For example, a protozoan parasite and the causative agent of Chagas disease in humans, Trypanosoma cruzi, recently colonized and spread through the city of Arequipa, Peru. We used population genomic and phylogenomic tools to analyze whole genomes of 123 T. cruzi isolates collected throughout Arequipa to determine patterns of T. cruzi dispersal. The data show significant population genetic structure within city blocks-parasites in the same block tend to be very closely related - but no population structure among blocks within districts - parasites in neighboring blocks are no more closely related to one another than to parasites in distant districts. These data suggest that T. cruzi dispersal within a block occurs regularly and that occasional long-range dispersal events allow the establishment of new T. cruzi populations in distant blocks. Movement of domestic animals may be the primary mechanism of inter-block and inter-district T. cruzi dispersal.Author SummaryUrbanization creates environments that are ideal for some human pests and pathogens. As the number and size of urban environments increases globally, it is becoming vital to understand how human disease-causing pathogens, their vectors, and their non-human hosts disperse through urban landscapes. Here we study a population of Trypanosoma cruzi – the protozoan parasite and causative agent of Chagas disease in humans – that recently colonized the city of Arequipa, Peru. We use population genomic and phylogenomic tools to understand how this parasite population dispersed through the city to achieve its current distribution and abundance. We show that T. cruzi collected from the same city block tend to be very closely related, while those from neighboring blocks are often as distantly related as those from blocks in distant districts. The data suggest that vectors facilitate frequent within-block dispersal of the parasite, while domestic animal movement may facilitate the relatively infrequent inter-block and interdistrict dispersal.
An anti-adhesive surface coating reduces adhesion during contact with cribellar threads in Pholcus phalangioides (Araneae, Pholcidae) but not in the web-owning spider Uloborus plumipes(Araneae, Uloboridae)
Authors: Frutiger Miriam , Kropf Christian 
Published: November 2019

AbstractCribellar threads are powerful tools for web spiders to catch and retain prey. Spiders encountering such threads, like cribellar web spiders or araneophagic spiders invading cribellar webs, should have a protective mechanism against the adhesion of these threads. We tested for an anti-adhesive surface coating in the web invader Pholcus phalangioides and the cribellate orb weaver Uloborus plumipes. We calculated an index of adhesion for differently treated legs of the two species in a cribellar U. plumipes capture thread, i.e. untreated legs, water-washed legs, and legs washed with the organic solvent n-hexane. The results show that legs of P. phalangioides stick significantly stronger when washed with n-hexane. Our interpretation is that P. phalangioides has an organic surface coating lowering the adhesive force of the cribellar thread. No such mechanism was found in U. plumipes.
An indigenousSaccharomyces uvarumpopulation with high genetic diversity dominates uninoculated Chardonnay fermentations at a Canadian winery
Authors: McCarthy Garrett C. , Morgan Sydney C. , Martiniuk Jonathan T. , Newman Brianne L. , Measday Vivien , Durall Daniel M. 
Published: November 2019

AbstractSaccharomyces cerevisiaeis the primary yeast species responsible for most fermentations in winemaking. However, other yeasts, includingSaccharomyces uvarum, have occasionally been found conducting commercial fermentations around the world.S. uvarumis typically associated with white wine fermentations in cool-climate wine regions, and has been identified as the dominant yeast in fermentations from France, Hungary, northern Italy, and, recently, Canada. However, little is known about how the origin and genetic diversity of the CanadianS. uvarumpopulation relates to strains from other parts of the world. In this study, a highly diverseS. uvarumpopulation was found dominating uninoculated commercial fermentations of Chardonnay grapes sourced from two different vineyards. Most of the strains identified were found to be genetically distinct fromS. uvarumstrains isolated around the world. Of the 106 strains ofS. uvarumidentified in this study, four played a dominant role in the fermentations, with some strains predominating in the fermentations from one vineyard over the other. Furthermore, two of the dominant strains were previously identified as dominant strains in uninoculated Chardonnay fermentations at the same winery two years earlier, providing evidence for a winery-resident population of indigenousS. uvarum. This research provides a valuable insight into the diversity and persistence of non-commercialS. uvarumstrains in North America, and provides a stepping stone for future work into the enological potential of an alternativeSaccharomycesyeast species.
Subjective value then confidence in human ventromedial prefrontal cortex
Authors: Shapiro Allison D. , Grafton Scott T. 
Published: November 2019

AbstractTwo fundamental goals of decision making are to select actions that maximize rewards while minimizing costs and to have strong confidence in the accuracy of a judgment. Neural signatures of these two forms of value: the subjective value (SV) of choice alternatives and the value of the judgment (confidence), have both been observed in ventromedial prefrontal cortex (vmPFC). However, the relationship between these dual value signals and their relative time courses are unknown. We recorded fMRI while 28 men and women performed a two-phase Ap-Av task with mixed-outcomes of monetary rewards paired with painful shock stimuli. Neural responses were measured during offer valuation (offer phase) and choice valuation (commit phase) and analyzed with respect to observed decision outcomes, model-estimated SV and confidence. During the offer phase, vmPFC tracked SV and decision outcomes, but it not confidence. During the commit phase, vmPFC tracked confidence, computed as the quadratic extension of SV, but it bore no significant relationship with the offer valuation itself, nor the decision. In fact, vmPFC responses from the commit phase were selective for confidence even for rejected offers, wherein confidence and SV were inversely related. Conversely, activation of the cognitive control network, including within lateral prefrontal cortex (lPFC) and dorsal anterior cingulate cortex (dACC) was associated with ambivalence, during both the offer and commit phases. Taken together, our results reveal complementary representations in vmPFC during value-based decision making that temporally dissociate such that offer valuation (SV) emerges before decision valuation (confidence).
SOX9 is required for kidney fibrosis and regulates NAV3 to control renal myofibroblast function in mice and humans
Authors: Raza Sayyid , Jokl Elliot , Pritchett James , Martin Katherine , Su Kim , Simpson Kara , Mullan Aoibheann F , Athwal Varinder , Doherty Daniel T , Zeef Leo , Henderson Neil C , Kalra Philip A , Hanley Neil A , Hanley Karen Piper 
Published: November 2019

AbstractRenal fibrosis is a common endpoint for many chronic kidney diseases. Extracellular matrix (ECM) from myofibroblasts causes progressive scarring and organ failure. The mechanisms underlying fibrogenesis and how it is sustained are incompletely understood. Here, we show that the transcription factor, Sex determining region Y-box 9 (SOX9), is required for kidney fibrosis. From genome-wide analysis we identify Neuron navigator 3 (NAV3) downstream of SOX9. NAV3 was upregulated in kidney disease in patients and following renal injury in mice colocalised with SOX9. By establishing an in vitro model of renal pericyte transition to myofibroblast we demonstrated that NAV3 is required for multiple aspects of fibrogenesis including actin polymerization linked to cell migration and sustaining SOX9 and active YAP1 levels. In summary, our work discovers novel SOX9-NAV3-YAP1/SOX9 circuitry as a new mechanism to explain the progression of kidney fibrosis and points to NAV3 as a novel target for pharmacological intervention.
A lifespan program of mouse synaptome architecture
Authors: Cizeron Mélissa , Qiu Zhen , Koniaris Babis , Gokhale Ragini , Komiyama Noboru H. , Fransén Erik , Grant Seth G.N. 
Published: November 2019

AbstractHow synapses change molecularly during the lifespan and across all brain circuits is unknown. We analyzed the protein composition of billions of individual synapses from birth to old age on a brain-wide scale in the mouse, revealing a program of changes in the lifespan synaptome architecture spanning individual dendrites to the systems level. Three major phases were uncovered, corresponding to human childhood, adulthood and old age. An arching trajectory of synaptome architecture drives the differentiation and specialization of brain regions to a peak in young adults before dedifferentiation returns the brain to a juvenile state. This trajectory underscores changing network organization and hippocampal physiology that may account for lifespan transitions in intellectual ability and memory, and the onset of behavioral disorders.One sentence summaryThe synaptome architecture of the mouse brain undergoes continuous changes that organize brain circuitry across the lifespan.
PHGDH supports liver ceramide synthesis and sustains lipid homeostasis
Authors: Kang Yun Pyo , Falzone Aimee , Liu Min , Saller James J. , Karreth Florian A. , DeNicola Gina M. 
Published: November 2019

AbstractBackgroundD-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown.MethodsTo study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter. With this model, PHGDH depletion can be globally induced in adult animals, while sparing the brain due to poor doxycycline delivery.ResultsWe found that PHGDH depletion is well tolerated and no overt phenotypes were observed in multiple highly proliferative cell compartments. Further, despite detectable knockdown, liver and pancreatic function were normal. Interestingly, diminished PHGDH expression in the liver reduced serine and ceramide levels without increasing the levels of deoxysphingolipids. Further, liver triacylglycerol profiles were altered, with an accumulation of longer chain, polyunsaturated tails upon PHGDH knockdown.ConclusionsThese results suggest that dietary serine is adequate to support the function of healthy, adult murine tissues, but PHGDH-derived serine supports liver ceramide synthesis and sustains general lipid homeostasis.
Tool recommender system in Galaxy using deep learning
Authors: Kumar Anup , Grüning Björn , Backofen Rolf 
Published: November 2019

AbstractGalaxy is a web-based and open-source scientific data-processing platform. Researchers compose pipelines in Galaxy to analyse scientific data. These pipelines, also known as workflows, can be complex and difficult to create from thousands of tools, especially for researchers new to Galaxy. To make creating workflows easier, faster and less error-prone, a predictive system is developed to recommend tools facilitating further analysis. A model is created to recommend tools by analysing workflows, composed by researchers on the European Galaxy server, using a deep learning approach. The higher-order dependencies in workflows, represented as directed acyclic graphs, are learned by training a gated recurrent units (GRU) neural network, a variant of a recurrent neural network (RNN). The weights of tools used in the neural network training are derived from their usage frequencies over a period of time. The hyper-parameters of the neural network are optimised using Bayesian optimisation. An accuracy of 97% in predicting tools is achieved by the model for precision@1, precision@2 and precision@3 metrics. It is accessed by a Galaxy API to recommend tools in real-time. Multiple user interface (UI) integrations on the server communicate with this API to apprise researchers of these recommended tools interactively.Contactkumara@informatik.uni-freiburg.degruening@informatik.uni-freiburg.debackofen@informatik.uni-freiburg.de
Purification and molecular characterization of phospholipase, antigen 5 and hyaluronidases from the venom of the Asian hornet (Vespa velutina)
Authors: Monsalve Rafael I. , Gutiérrez Ruth , Hoof Ilka , Lombardero Manuel 
Published: November 2019

AbstractThe aim of this study was to purify potential allergenic components of Vespa velutina venom, the yellow legged Asian Hornet, and perform a preliminary characterization of the purified proteins. Starting from the whole venom of V.velutina, several chromatographic steps allowed to purify the phospholipase (named Vesp v 1), as well as the antigen 5 (Vesp v 5, the only allergenic component described as such so far). The two hyaluronidase isoforms found (Vesp v 2A and Vesp v 2B) cannot be separated from each other, but they are partially purified and characterized. Purity of the isolated proteins in shown by SDSPAGE, as well as by the results of the N-terminal sequencing. This characterization and nLC-MS/MS data provide most of the sequence for Vesp v 1 and Vesp v 5 (72 and 84% coverage, respectively), confirming that the whole sequences of the isolated natural components match with the data available in public transcriptomic databases. It is of particular interest that Vesp v 1 is a glycosylated phospholipase, a fact that had only described so far for the corresponding allergen components of Dolichovespula maculata and Solenopsis invicta.The availability of the complete sequences of Vespa velutina components permits comparison with homologous sequences from other Hymenoptera. These data demonstrate the higher similarity among the species of the genera Vespa and Vespula, in comparison to Polistes species, as it is especially observed with the hyaluronidases isoforms: the isoform Vesp v 2A only exists in the former genera, and not in Polistes; in addition, the most abundant isoform (Vesp v 2B) exhibits 93% sequence identity with the Ves v 2 isoform of Vespula vulgaris.Finally, the isolated components might be useful for improving the diagnosis of patients that could be allergic to stings of this invasive Asian hornet, as it has been the case of an improved diagnosis and treatment of other Hymenoptera-sensitized patients.Data Availability StatementProteomic study data are deposited and made available publicly when data are published with the ProteomeExchange identifier PXD015381 in the Mass spectrometry Interactive Virtual Environment (MassIVE).Allergen nomenclature for Vesp v 5 (and also for any future demonstrated allergen from Vespa velutina) has been approved by the WHO/IUIS Committee (www.allergen.org); when this manuscript is accepted, the WHO/IUIS Committee will be informed so that the complete sequences included in this manuscript are also included in their database (with links to the UNIPROT database, who will also be informed that the data can be made public).
Functional hyperemia drives fluid exchange in the paravascular space
Authors: Kedarasetti Ravi Teja , Turner Kevin L. , Echagarruga Christina , Gluckman Bruce G. , Drew Patrick J. , Costanzo Francesco 
Published: November 2019

AbstractMaintaining the ionic and chemical composition of the extracellular spaces in the brain is extremely important for its health and function. However, the brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that the fluid movement through the paravascular space (PVS) surrounding penetrating arteries can help remove metabolites from the brain. The dynamics of fluid movement in the PVS and its interaction with arterial dilation and brain mechanics are not well understood. Here, we performed simulations to understand how arterial pulsations and dilations interact with brain deformability to drive fluid flow in the PVS. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. In contrast, when the artery dilated with dynamics like those seen during functional hyperemia, there was a marked movement of fluid through the PVS. Our simulations suggest that in addition to its other purposes, functional hyperemia may serve to increase fluid exchange between the PVS and the subarachnoid space, improving the clearance of metabolic waste. We measured displacement of the blood vessels and the brain tissue simultaneously in awake, head-fixed mice using two-photon microscopy. Our measurements show that brain tissue can deform in response to fluid movement in the PVS, as predicted by simulations. The results from our simulations and experiments show that the deformability of the soft brain tissue needs to be accounted for when studying fluid flow and metabolite transport in the brain.