bluuebunny/crossref_metadata_2025_split huggingface dataset:
A convolutional neural-network framework for modelling auditory sensory cells and synapses
Authors: Drakopoulos Fotios , Baby Deepak , Verhulst Sarah 
Published: November 2020

AbstractIn classical computational neuroscience, analytical model descriptions are derived from neuronal recordings to mimic the underlying biological system. These neuronal models are typically slow to compute and cannot be integrated within large-scale neuronal simulation frameworks. We present a hybrid, machine-learning and computational-neuroscience approach that transforms analytical models of sensory neurons and synapses into deep-neural-network (DNN) neuronal units with the same biophysical properties. Our DNN-model architecture comprises parallel and differentiable equations that can be used for backpropagation in neuro-engineering applications, and offers a simulation run-time improvement factor of 70 and 280 on CPU or GPU systems respectively. We focussed our development on auditory neurons and synapses, and show that our DNN-model architecture can be extended to a variety of existing analytical models. We describe how our approach for auditory models can be applied to other neuron and synapse types to help accelerate the development of large-scale brain networks and DNN-based treatments of the pathological system.
Evaluation and refinement of sample preparation methods for extracellular matrix proteome coverage
Authors: McCabe Maxwell C. , Schmitt Lauren R. , Hill Ryan C. , Dzieciatkowska Monika , Maslanka Mark , Daamen Willeke F. , van Kuppevelt Toin H. , Hof Danique J. , Hansen Kirk C. 
Published: November 2020

ABSTRACTThe extracellular matrix is a key component of tissues, yet it is under-represented in proteomic datasets. Identification and evaluation of proteins in the extracellular matrix (ECM) has proved challenging due to the insolubility of many ECM proteins in traditional protein extraction buffers. Here we separate the decellularization and ECM extraction steps of several prominent methods for evaluation under real-world conditions. The results are used to optimize a two-fraction ECM extraction method. Approximately one dozen additional parameters are tested and recommendations for analysis based on overall ECM coverage or specific ECM classes are given. Compared to a standard in-solution digest, the optimized method yielded a 4-fold improvement in unique ECM peptide identifications.Abstract Figure
Monitoring single-cell dynamics of entry into quiescence during an unperturbed lifecycle
Authors: Jacquel Basile , Aspert Théo , Laporte Damien , Sagot Isabelle , Charvin Gilles 
Published: November 2020

AbstractThe life cycle of microorganisms is associated with dynamic metabolic transitions and complex cellular responses. In yeast, how metabolic signals control the progressive choreography of structural reorganizations observed in quiescent cells during a natural life cycle remains unclear. We have developed an integrated microfluidic device to address this question, enabling continuous single-cell tracking in a batch culture experiencing unperturbed nutrient exhaustion to unravel the coordination between metabolic and structural transitions within cells. Our technique reveals an abrupt fate divergence in the population, whereby a fraction of cells is unable to transition to respiratory metabolism and undergoes a reversible entry into a quiescence-like state leading to premature cell death. Further observations reveal that non-monotonous internal pH fluctuations in respiration-competent cells orchestrate the successive waves of protein super-assemblies formation that accompany the entry into abona fidequiescent state. This ultimately leads to an abrupt cytosolic glass transition that occurs stochastically long after proliferation cessation. This new experimental framework provides a unique way to track single-cell fate dynamics over a long timescale in a population of cells that continuously modify their ecological niche.
Effect of Increasing Glucose Concentration on Estimation of Electrolytes by ion selective electrode
Authors: Khidir Omalkhair A. , Osman Mohammed Elsheikh 
Published: November 2020

AbstractBackgroundThe measurement of serum electrolytes like sodium (Na+), potassium (K+) is routinely performed in clinical biochemistry laboratories using ion-selective electrodes (ISE).AimTo minimize error and test the effect of increasing glucose concentration on estimation of sodium and potassium.Materials and MethodsRandomly selected sera samples submitted for routine biochemical estimations were pooled for the study. A stock solution of glucose with concentration of 20 g/ dL was prepared by dissolving anhydrous glucose in normal saline (0.9 % NaCl). Next the pooled sera was divided into several aliquots with 1.0 ml sera each and increasing amounts of the stock solution were added to the different aliquots so as to generate glucose concentrations ranging from around 100 mg/dL to about 3000 mg/dL.Resultsthe glucose concentration of different serum aliquots obtained on cobas c311(roche system) were found to rang from 110 to 2577 mg/dl. The mean of sodium by direct ion selective 142±0.52 mmol/l, values showed in significant difference (p=0.320).The mean of sodium by indirect ion selective 143 ± 0.72 mmol/l, values showed significant difference (p< 0.05). And the mean of potassium by direct ion selective 3.54 ±0.29 mmol/l, values showed significant difference (p< 0.05).The mean of potassium by indirect ion selective 3.53±0.26 mmol/l, values showed significant difference (p< 0.05).ConclusionsIncreasing blood gluose interferance in electrlytes mainly potasssium by both direct and indirect ion selective electrode, whenincreasing glucose potassium decreae significantly No different significant between direct and indirect ion selective electrods in potassium when used cobas c311 and easy lyte.Significant interferance in sodium by indirect ion selective electrodewhile no significant interferance in sodium direct ion selective electrode.Glucose concentration interfer the electrolyte specially potassium in concentration more than 1700 mg/dl by direct and indirect methods.
Sodium Pyruvate Ameliorates Influenza A Virus InfectionIn Vivo
Authors: Reel Jessica M. , Lupfer Christopher R. 
Published: November 2020

AbstractInfluenza A virus (IAV) causes seasonal epidemics annually and pandemics every few decades. Most antiviral treatments used for IAV are only effective if administered during the first 48 hours of infection and antiviral resistance is possible. Therapies that can be initiated later during IAV infection and that are less likely to elicit resistance will significantly improve treatment options. Pyruvate, a key metabolite, and end product of glycolysis, has been studied for many uses, including its anti-inflammatory capabilities. Sodium pyruvate was recently shown by us to decrease inflammasome activation during IAV infection. Here, we investigated sodium pyruvate’s effects on IAVin vivo.We found that nebulizing mice with sodium pyruvate decreased morbidity and weight loss during infection. Additionally, treated mice consumed more chow during infection indicating improved symptoms. There were notable improvements in pro-inflammatory cytokine production (IL-1β) and lower virus titers on days 7 post-infection in mice treated with sodium pyruvate compared to control animals. As pyruvate acts on the host immune response and metabolic pathways and not directly on the virus, our data demonstrate that sodium pyruvate is a promising treatment option that is safe, effective, and unlikely to elicit antiviral resistance.
CaMKII activation triggers persistent formation and segregation of postsynaptic liquid phase
Authors: Hosokawa Tomohisa , Liu Pin-Wu , Cai Qixu , Ferreira Joana S. , Levet Florian , Butler Corey , Sibarita Jean-Baptiste , Choquet Daniel , Groc Laurent , Hosy Eric , Zhang Mingjie , Hayashi Yasunori 
Published: November 2020

AbstractTransient information input to brain leads to persistent changes in synaptic circuit, thereby forming memory engrams. Synapse undergoes coordinated functional and structural changes during this process but how such changes are achieved by its component molecules still largely remain enigmatic. We found that activated CaMKII, the central player of synaptic plasticity, undergoes liquid-liquid phase separation (LLPS) with NMDAR subunit GluN2B. Due to CaMKII autophosphorylation, the condensate stably persists even after Ca2+is removed. The selective binding of activated CaMKII with GluN2B co-segregates AMPAR/neuroligin (NLGN) into a phase-in-phase assembly. Because postsynaptic NLGN clusters presynaptic neurexin and other active zone proteins thereby increasing the release probability of synaptic vesicles, this ensures efficient synaptic transmission. In this way, Ca2+-induced and persistent formation of LLPS by CaMKII serves as molecular basis of memory by functioning as an activity-dependent crosslinker for postsynaptic proteins and segregating trans-synaptic nanocolumns.
Bovine serum albumin as an immunogenic carrier facilitating the development of hapten-specific monoclonal antibodies
Authors: Zhao Ruotong , Jiang Mingjun 
Published: November 2020

AbstractThere is a common misconception that the generation of hapten-specific monoclonal antibodies (mAbs) requires the use of a heterologous conjugate to ensure carrier-specific antibodies not being detected. In this study, salbutamol (SAL) was used as a model hapten to exhibit the benefits of bovine serum albumin (BSA) as a carrier for developing hapten-specific mAbs. SAL-BSA conjugate would serve as both an immune antigen and a screening antigen during the preparation of SAL-specific mAbs. Six hybridomas were identified to secret mAbs specific for free SAL with minor or negligible cross-reactivity with other β-agonists. Meanwhile, none of hybrodomas secreting anti-BSA antibodies were screened out even though the fetal bovine serum (FBS) added to the medium decreased from 10% to 1% (v/v). Based on one of the six mAbs, 3F12, a direct competitive enzyme-linked immunosorbent assay (dcELISA) was developed for meausring SAL. Under the optimized assay, the quantitative working range was from 312.5 to 20,000 pg/mL (R2= 0.9959), with a limit of detection (LOD) of 142.9 pg/mL. The results showed that BSA is an efficient and suitable protein carrier for facilitating the development of hapten-specific mAbs.
Population genomics of the pathogenic yeast Candida tropicalis identifies hybrid isolates in environmental samples
Authors: O’Brien Caoimhe E. , Oliveira-Pacheco João , Cinnéide Eoin Ó , Hasse Max A. B. , Hittinger Chris Todd , Rogers Thomas R. , Zaragoza Oscar , Bond Ursula , Butler Geraldine 
Published: November 2020

AbstractCandida tropicalis is a human pathogen that primarily infects the immunocompromised. Whereas the genome of one isolate, C. tropicalis MYA-3404, was originally sequenced in 2009, there have been no large-scale, multi-isolate studies of the genetic and phenotypic diversity of this species. Here, we used whole genome sequencing and phenotyping to characterize 77 isolates C. tropicalis isolates from clinical and environmental sources from a variety of locations. We show that most C. tropicalis isolates are diploids with approximately 2 - 6 heterozygous variants per kilobase. The genomes are relatively stable, with few aneuploidies. However, we identified one highly homozygous isolate and six isolates of C. tropicalis with much higher heterozygosity levels ranging from 36 - 49 heterozygous variants per kilobase. Our analyses show that the heterozygous isolates represent two different hybrid lineages, where the hybrids share one parent (A) with most other C. tropicalis isolates, but the second parent (B or C) differs by at least 4% at the genome level. Four of the sequenced isolates descend from an AB hybridization, and two from an AC hybridization. The hybrids are MTLa/α heterozygotes. Hybridization, or mating, between different parents is therefore common in the evolutionary history of C. tropicalis. The new hybrids were predominantly found in environmental niches, including from soil. Hybridization is therefore unlikely to be associated with virulence. In addition, we used genotype-phenotype correlation and CRISPR-Cas9 editing to identify a genome variant that results in the inability of one isolate to utilize certain branched-chain amino acids as a sole nitrogen source.Author summaryCandida tropicalis is an important fungal pathogen, which is particularly common in the Asia-Pacific and Latin America. There is currently very little known about the diversity of genotype and phenotype of C. tropicalis isolates. By carrying out a phylogenomic analysis of 77 isolates, we find that C. tropicalis genomes range from very homozygous to highly heterozygous. We show that the heterozygous isolates are hybrids, most likely formed by mating between different parents. Unlike other Candida species, the hybrids are more common in environmental than in clinical niches, suggesting that for this species, hybridization is not associated with virulence. We also explore the range of phenotypes, and we identify a genomic variant that is required for growth on valine and isoleucine as sole nitrogen sources.
Pharyngeal pumping and tissue-specific transgenic P-glycoprotein expression influence macrocyclic lactone susceptibility inCaenorhabditis elegans
Authors: Gerhard Alexander P. , Krücken Jürgen , Neveu Cedric , Charvet Claude L. , Harmache Abdallah , von Samson-Himmelstjerna Georg 
Published: November 2020

AbstractMacrocyclic lactone (ML) resistance has emerged in many parasitic nematodes including the pathogenic horse roundwormParascaris univalens. The underlying mechanism of ML resistance and the drug penetration routes into the nematodes remain to be elucidated. Drug efflux by P-glycoproteins is considered a potential resistance mechanism but conclusive functional evidence is lacking. To this end, we used a motility assay modified to stimulate pharyngeal pumping (PP) by bacteria or serotonin and tissue-specific expression ofPun-PGP-9 in the free-living model nematodeCaenorhabditis elegans. Here, stimulation of PP was identified as an important factor forC. elegansML susceptibility, increasing the EC50values of ivermectin by up to 11.1-fold and of moxidectin by 1.2-fold. In this context, intestinalPun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation, increasing the EC50values by approximately 3- to 4-fold (ivermectin) or by < 1.3-fold (moxidectin). Conversely, epidermalPun-PGP-9 expression protected against moxidectin regardless of PP with EC50fold changes below 1.5 but against ivermectin with a considerable 2.9-fold EC50increase only when the drug is not actively ingested. Our results highlight the role of active drug ingestion by nematodes for susceptibility and provide conclusive functional evidence for a contribution of P-glycoproteins to ML resistance.Author SummaryParasitic nematode infections pose a serious threat to animal health, in particular in light of the widespread anthelmintic resistance in different nematode species. In equines, the roundwormParascaris univalensis a major pathogen of foals, exhibiting widespread resistance against macrocyclic lactones (MLs). This represents a particular challenge to animal health, but the underlying mechanisms and drug penetration routes remain mostly unknown. P-glycoprotein ABC-transporters have been linked to ML resistance in several parasitic nematodes. Here we demonstrate by tissue-specific overexpression ofPun-PGP-9 in the free-living model nematodeCaenorhabditis eleganstheir ability to reduce the susceptibility to two commonly used MLs, ivermectin and moxidectin. At the same time, active drug ingestion by pharyngeal pumping (PP) strongly enhanced ivermectin and moderately effects moxidectin susceptibility. In more detail, the effect of intestinal or epidermalPun-PGP-9 was dependent on active drug ingestion. These observations indicate differences in the drug penetration routes between ML derivatives and allow novel insight into the functional role of P-glycoproteins.
Pattern Recognition Receptor based Prognostic Biomarkers for predicting Survival of Uterine Corpus Endometrial Cancer Patients
Authors: Kaur Dilraj , Arora Chakit , Raghava G.P.S 
Published: November 2020

AbstractIn this study, we attempted to identify prognostic biomarkers for predicting survival risk of uterine corpus endometrial cancer (UCEC) patients from the gene expression profile of pattern recognition receptors (PRRs). A wide range of feature selection techniques have been tried, including network-based methods to identify a small number of genes from 331 PRR genes. Firstly, a risk stratification model has been developed using biomarker genes selected using a network-based approach and achieved HR=1.37 with p=0.294. Secondly, we developed a risk stratification model using biomarker of seven genes obtained from clustering and achieved HR=9.14 and p= 1.49×10-12. Finally, we developed various combinatorial models using biomarker of 15 PRR genes that were significantly associated with UCEC survival. We found that a multiple genes-based risk stratification model using nine genes (CLEC1B, CLEC3A, IRF7, CTSB, FCN1, RIPK2, NLRP10, NLRP9 and SARM1) gave the best result (HR=10.70, p=1.1×10-12, C=0.76, log-rank-p=8.15×10-14). The performance of this model improved significantly when we used the clinical stage of patients in combination with the expression of nine genes and achieved HR=15.23 (p=2.21×10-7, C=0.78, log-rank-p=2.76×10-17). We also developed classification models that can classify high-risk patients (survive ≤ 4.3 years) and low-risk patients (survive > 4.3 years) and achieved AUROC of 0.86. It was observed that specific genes are positively correlated with overall survival of UCEC patients. Based on these observations, we identified potential immunotherapeutic agents for treating UCEC patients.
Modelling optically pumped magnetometer interference as a mean (magnetic) field
Authors: Tierney Tim M , Alexander Nicholas , Mellor Stephanie , Holmes Niall , Seymour Robert , O’Neill George C , Maguire Eleanor A , Barnes Gareth R 
Published: November 2020

AbstractHere we propose that much of the magnetic interference observed when using optically pumped magnetometers can be modeled spatially as a mean (magnetic) field. We show that this approximation reduces sensor level variability and substantially improves statistical power. This model does not require knowledge of the underlying neuroanatomy nor the sensor positions. It only needs information about the sensor orientation. Due to the model’s low rank there is little risk of removing substantial neural signal. However, we provide a framework to assess this risk for any sensor number, design or subject neuroanatomy. We find that the risk of unintentionally removing neural signal is reduced when multi-axis recordings are performed. We validated the method using a binaural auditory evoked response paradigm and demonstrated that the mean field correction increases reconstructed SNR in relevant brain regions in both the spatial and temporal domain. Considering the model’s simplicity and efficacy, we suggest that this mean field correction can be a powerful preprocessing step for arrays of optically pumped magnetometers.
An adaptive optics module for deep tissue multiphoton imaging in vivo
Authors: Rodríguez Cristina , Chen Anderson , Rivera José A. , Mohr Manuel A. , Liang Yajie , Sun Wenzhi , Milkie Daniel E. , Bifano Thomas G. , Chen Xiaoke , Ji Na 
Published: November 2020

ABSTRACTUnderstanding complex biological systems requires visualizing structures and processes deep within living organisms. We developed a compact adaptive optics module and incorporated it into two- and three-photon fluorescence microscopes, to measure and correct tissue-induced aberrations. We resolved synaptic structures in deep cortical and subcortical areas of the mouse brain, and demonstrated high-resolution imaging of neuronal structures and somatosensory-evoked calcium responses in the mouse spinal cord at unprecedented depths in vivo.
Identification of RNAs bound by Hfq reveals widespread RNA partners and a sporulation regulator in the human pathogenClostridioides difficile
Authors: Boudry Pierre , Piattelli Emma , Drouineau Emilie , Peltier Johann , Boutserin Anaïs , Lejars Maxence , Hajnsdorf Eliane , Monot Marc , Dupuy Bruno , Martin-Verstraete Isabelle , Gautheret Daniel , Toffano-Nioche Claire , Soutourina Olga 
Published: November 2020

ABSTRACTNoncoding RNAs (ncRNA) have emerged as important components of regulatory networks governing bacterial physiology and virulence. Previous deep-sequencing analysis identified a large diversity of ncRNAs in the human enteropathogenClostridioides (Clostridium) difficile.Some of them aretrans-encoded RNAs that could require the RNA chaperone protein Hfq for their action. Recent analysis suggested a pleiotropic role of Hfq inC. difficilewith the most pronounced effect on sporulation, a key process during the infectious cycle of this pathogen. However, a global view of RNAs interacting withC. difficileHfq is missing. In the present study, we performed RNA immunoprecipitation high-throughput sequencing (RIP-Seq) to identify Hfq-associated RNAs inC. difficile. Our work revealed a large set of Hfq-interacting mRNAs and ncRNAs, including mRNA leaders and coding regions, known and potential new ncRNAs. In addition totrans-encoded RNAs, new categories of Hfq ligands were found includingcis-antisense RNAs, riboswitches and CRISPR RNAs. ncRNA-mRNA and ncRNA-ncRNA pairings were postulated through computational predictions. Investigation of one of the Hfq-associated ncRNAs, RCd1, suggests that this RNA contributes to the control of late stages of sporulation inC. difficile. Altogether, these data provide essential molecular basis for further studies of post-transcriptional regulatory network in this enteropathogen.
The mutational landscape of human somatic and germline cells
Authors: Moore Luiza , Cagan Alex , Coorens Tim H.H. , Neville Matthew D.C. , Sanghvi Rashesh , Sanders Mathijs A. , Oliver Thomas R.W. , Leongamornlert Daniel , Ellis Peter , Noorani Ayesha , Mitchell Thomas J , Butler Timothy M. , Hooks Yvette , Warren Anne Y. , Jorgensen Mette , Dawson Kevin J. , Menzies Andrew , O’Neill Laura , Latimer Calli , Teng Mabel , van Boxtel Ruben , Iacobuzio-Donahue Christine A. , Martincorena Inigo , Heer Rakesh , Campbell Peter J. , Fitzgerald Rebecca C. , Stratton Michael R. , Rahbari Raheleh 
Published: November 2020

AbstractDuring the course of a lifetime normal human cells accumulate mutations. Here, using multiple samples from the same individuals we compared the mutational landscape in 29 anatomical structures from soma and the germline. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types but their absolute and relative contributions varied substantially. SBS18, potentially reflecting oxidative damage, and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The mutation rate was lowest in spermatogonia, the stem cell from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutation processes and may be partially attributable to a low cell division rate of basal spermatogonia. The results provide important insights into how mutational processes affect the soma and germline.