bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ impedance measurements on postmortem porcine brain
Authors: Poßner Lucas , Laukner Matthias , Wilhelmy Florian , Lindner Dirk , Pliquett Uwe , Petkovic Bojana , Ziolkowski Marek , Knösche Thomas R. , Weise Konstantin 
Published: April 2020

AbstractThe paper presents an experimental study where the distinctness of grey and white matter of an in situ postmortem porcine brain by impedance measurements is investigated. Experimental conditions that would allow to conduct the same experiment on in vivo human brain tissue are replicated.https://doi.org/10.1515/cdbme-2019-XXXX
Molecular rationale for hantavirus neutralization by a reservoir host-derived monoclonal antibody
Authors: Rissanen Ilona , Stass Robert , Krumm Stefanie A. , Seow Jeffrey , Hulswit Ruben J.G. , Paesen Guido C. , Hepojoki Jussi , Vapalahti Olli , Lundkvist Åke , Reynard Olivier , Volchkov Viktor , Doores Katie J. , Huiskonen Juha T. , Bowden Thomas A. 
Published: April 2020

AbstractThe intricate lattice of Gn and Gc glycoprotein spike complexes at the surface of hantaviruses facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Here, through study of a neutralizing monoclonal antibody (mAb 4G2) generated in a bank vole reservoir host following infection with Puumala virus (PUUV), we provide molecular-level insights into how antibody-mediated targeting of the hantaviral glycoprotein lattice effectively neutralizes the virus. Crystallographic analysis reveals that mAb 4G2 binds to a multi-domain site on Gc in the pre-fusion state, and that Fab binding is incompatible with the conformational changes of the Gc that are required for host cell entry. Cryo-electron microscopy of PUUV-like particles treated with Fab 4G2 demonstrates that the antibody binds to monomeric Gc at breaks in the Gn-Gc lattice, highlighting the immunological accessibility of Gc monomers on the mature hantavirus surface and the plastic nature of the higher-order lattice assembly. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.
Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes
Authors: Mármol-Sanchez Emilio , Luigi-Sierra María Gracia , Castelló Anna , Guan Dailu , Quintanilla Raquel , Tonda Raul , Amills Marcel 
Published: April 2020

AbstractBackgroundMature microRNAs (miRNAs) play an important role in repressing the expression of a wide range of mRNAs. The variability of miRNA genes and their corresponding 3’UTR binding sites might disrupt canonical conserved miRNA-mRNA pairing, thus modifying gene expression patterns. The presence of polymorphic sites in miRNA genes and their association with gene expression phenotypes and complex traits has been poorly characterized in pigs so far.ResultsBy analyzing whole-genome sequences from 120 pigs and wild boars from Europe and Asia, we have identified 285 single nucleotide polymorphisms (SNPs) mapping to miRNA loci, as well as 109,724 SNPs located in predicted 7mer-m8 miRNA binding sites within porcine 3’UTRs. Porcine miRNA genes show a reduced SNP density compared with their flanking non-miRNA regions. By sequencing the genomes of 5 Duroc boars, we have identified 12 miRNA SNPs that have been subsequently genotyped in their offspring (N = 345, Lipgen population). Association analyses between miRNA SNPs and 38 lipid-related traits as well as hepatic and muscle microarray expression phenotypes recorded in the Lipgen population were carried out. The most relevant association detected was the one between the genotype of the rs319154814 (G/A) SNP located in the apical loop of the ssc-miR-326 hairpin precursor andPPP1CCmRNA levels in the liver (q-value = 0.058). This result was subsequently confirmed by qPCR (P-value = 0.027). The rs319154814 (G/A) genotype was also associated with several fatty acid composition traits.ConclusionsPorcine miRNA genes show a reduced variability consistent with strong purifying selection, particularly in the seed region, which plays a critical role in miRNA binding. Although it is generally assumed that SNPs mapping to the seed region are the ones with the strongest consequences on mRNA expression, we show that a SNP mapping to the apical region of ssc-miR-326 is significantly associated with the hepatic mRNA levels of thePPP1CCgene, one of its predicted targets. Although experimental confirmation of such interaction has been obtained in humans but not in pigs, this result highlights the need of further investigating the functional effects of miRNA polymorphisms located outside the seed region on gene expression in pigs.
Organ-on-a-chip model of vascularized human bone marrow niches
Authors: Glaser Drew E. , Curtis Matthew B. , Sariano Peter A. , Rollins Zachary A. , Shergill Bhupinder S. , Anand Aravind , Deely Alyssa M. , Shirure Venktesh S. , Anderson Leif , Lowen Jeremy M. , Ng Natalie R. , Weilbaecher Katherine , Link Daniel C. , George Steven C. 
Published: April 2020

AbstractAnimal models of bone marrow have limited spatial and temporal resolution to observe biological events (intravasation and cellular egress) and are inadequate to dissect dynamic events at the niche level (100 microns). Utilizing microfluidic and stem cell technology, we present a 3Din vitromodel of human bone marrow that contains perivascular and endosteal niches complete with dynamic, perfusable vascular networks. We demonstrate that our model can performin vivofunctions including maintenance and differentiation of CD34+hematopoietic stem/progenitor cells (HSPC) for up to fourteen days, egress of myeloid progenitors, and expression of markers consistent within vivohuman bone marrow. The platform design enables the addition of tissue niches at a later timepoint to probe mechanisms such as tumor cell migration. Overall, we present a novel organ-on-a-chip platform that is capable of recapitulating the human bone marrow microenvironment to observe hematopoietic phenomena at high spatial and temporal resolution.
Microbial communities in an ultra-oligotrophic sea are more affected by season than by distance from shore
Authors: Haber Markus , Rosenberg Dalit Roth , Lalzar Maya , Burgsdorf Ilia , Saurav Kumar , Lionheart Regina , Lehahn Yoav , Aharonovich Dikla , Sher Daniel , Krom Michael D. , Steindler Laura 
Published: April 2020

AbstractMarine microbial communities vary seasonally and spatially, but these two factors are rarely addressed together. We studied temporal and spatial patterns of the microbial community structure and activity along a coast to offshore transect from the Israeli coast of the Eastern Mediterranean Sea (EMS) over six cruises, in three seasons of two consecutive years. The ultra-oligotrophic status of the South Eastern Mediterranean Sea was reflected in the microbial community composition that was dominated by oligotrophic microbial groups such as SAR11 throughout the year, even at the most coastal station sampled. Seasons affected microbial communities much more than distance from shore explaining about half of the observed variability in the microbial community, compared to only about 6% that was explained by station. However, the most coastal site differed significantly in community structure and activity from the three further offshore stations in early winter and summer, but not in spring. Our data on the microbial community composition and its seasonality from a transect into the South Eastern Levantine basin support the notion that the EMS behaves similar to open gyres rather than an inland sea.
Cyclical Regression Covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasitePlasmodium falciparum
Authors: Foster Gabriel J. , Button-Simons Katrina , Vendrely Katelyn , Romero-Severson Jeanne , Ferdig Michael T. 
Published: April 2020

AbstractBackgroundThe cyclical nature of parasite gene expression in the intraerythrocytic development cycle (IDC) in human blood confounds the accurate detection of specific transcriptional differences due to drug resistance inPlasmodium falciparum. Here, we propose the use of cyclical regression covariates to eliminate the major confounding of developmentally driven transcriptional changes with changes due to drug response. We show that elimination of this confounding can reduce both Type I and Type II errors, and demonstrate the effect of approach on real data.ResultsWe apply this method to two publicly available datasets, and demonstrate its ability to reduce the potential confounding of differences in expression due the species-specific intraerythrocytic development cycle from strain-specific differences in drug response. We show that the application of cyclical regression covariates has minimal impact on the pool of transcripts identified as significantly different in a dataset generated from single timepoint clinical blood samples with low variance for developmental stage and a profound impact on another clinical data set with more variance among the samples for developmental stage.ConclusionsCyclical regression covariates have immediate application to studies wherein-vitrosynchronization of all samples to the same developmental timepoint is not feasible, primarily parasite transcriptome sequencing direct from clinical blood samples, a widely used approach to frontline detection of emerging drug resistance.
Tensorpac : an open-source Python toolbox for tensor-based Phase-Amplitude Coupling measurement in electrophysiological brain signals
Authors: Combrisson Etienne , Nest Timothy , Brovelli Andrea , Ince Robin A.A. , Soto Juan LP , Guillot Aymeric , Jerbi Karim 
Published: April 2020

AbstractDespite being the focus of a thriving field of research, the biological mechanisms that underlie information integration in the brain are not yet fully understood. A theory that has gained a lot of traction in recent years suggests that multi-scale integration is regulated by a hierarchy of mutually interacting neural oscillations. In particular, there is accumulating evidence that phase-amplitude coupling (PAC), a specific form of cross-frequency interaction, plays a key role in numerous cognitive processes. Current research in the field is not only hampered by the absence of a gold standard for PAC analysis, but also by the computational costs of running exhaustive computations on large and high-dimensional electrophysiological brain signals. In addition, various signal properties and analyses parameters can lead to spurious PAC. Here, we present Tensorpac, an open-source Python toolbox dedicated to PAC analysis of neurophysiological data. The advantages of Tensorpac include (1) higher computational efficiency thanks to software design that combines tensor computations and parallel computing, (2) the implementation of all most widely used PAC methods in one package, (3) the statistical analysis of PAC measures, and (4) extended PAC visualization capabilities. Tensorpac is distributed under a BSD-3-Clause license and can be launched on any operating system (Linux, OSX and Windows). It can be installed directly via pip or downloaded from Github (https://github.com/EtienneCmb/tensorpac). By making Tensorpac available, we aim to enhance the reproducibility and quality of PAC research, and provide open tools that will accelerate future method development in neuroscience.
Role of TRPV1 in colonic mucin production and gut microbiota profile
Authors: Kumar Vijay , Mahajan Neha , Khare Pragyanshu , Kondepudi Kanthi Kiran , Bishnoi Mahendra 
Published: April 2020

ABSTRACTPURPOSEThis study focuses on exploring the role of sensory cation channel Transient Receptor Potential channel subfamily Vanilloid 1 (TRPV1) in gut health, specifically mucus secretion and microflora profile in gut.METHODS AND RESULTSWe employed resiniferatoxin (ultrapotent TRPV1 agonist) induced chemo-denervation model in rats and studied the effects of TRPV1 ablation on gut mucus secretion patterns. Histological and transcriptional analysis showed substantial decrease in mucus production as well as in expression of genes involved in goblet cells differentiation, mucin production and glycosylation. 16S metagenome analysis revealed changes in abundance of various gut bacteria, including decrease in beneficial bacteria likeLactobacillus sppandClostridia spp.Also, TRPV1 ablation significantly decreased the levels of short chain fatty acids,i.e.acetate and butyrate.CONCLUSIONThe present study provides first evidence that systemic TRPV1 ablation leads to impairment in mucus secretion and causes dysbiosis in gut. Further, it suggests to address mucin production and gut microbiota related adverse effects during the development of TRPV1 antagonism/ablation-based therapeutic and preventive strategies.
A Zinc-dependent metalloproteinase in the intracellular adaptation ofBrucella abortusin macrophages
Authors: Gómez Leonardo A. , Alvarez Francisco I. , Molina Raúl , Soto Rodrigo , Daza-Castro Carla , Flores Manuel , León Yrvin , Oñate Angel A. 
Published: April 2020

AbstractBrucella abortusis a pathogen that survives in macrophages. Several virulence factors participate in this process, including the open reading frame (ORF) BAB1_0270 codifying of a Zinc-dependent metalloproteinase. Here, its contribution in the process of intracellular adaptation was analyzed by infecting RAW264.7 macrophages with the mutantB. abortus Δ270 strain. Results showed that this Zinc-dependent metalloproteinase is a cytoplasmic protein that conforms an operon with a transcriptional regulator, which may constitute a type II toxin-antitoxin system. Functionally, this Zinc-dependent metalloproteinase participated neither in the adherence nor the initial intracellular traffic ofB. abortusin macrophages. Nevertheless, its deletion significantly increased the co-localization ofB. abortus Δ270 with phagolysosomal cathepsin D, reducing both its co-localization with calnexin, present in endoplasmic reticulum derived vesicles, and its intracellular replication within macrophages. Besides,B. abortus Δ270-infected macrophages produced significantly higher levels of TNF-α, IL-6, CD80 and CD86 thanB. abortus2308, even when several genes involved in virulence (vjbR,hutC,bvrR,virB1) were up-regulated in this mutant. Finally, its deletion significantly reduced the capacity ofB. abortus Δ270 to adapt, grow and express several virulence factors under acidic conditions. Based on these results, we discuss the role of this Zinc-dependent metalloproteinase in the regulation of the virulence of this pathogen, concluding that it contributes significantly to the intracellular adaptation ofB. abortus2308 during the infection of macrophages.Author summaryBrucella abortusis the causative agent of the brucellosis, a highly contagious diseases. A Zinc-dependent metalloproteinase contributes significantly in the intracellular survival. Here, we demonstrate that this metalloproteinase has homology with ImmA/IrrE proteases, which are involved in the bacterial resistance to hostile environment. Furthermore, it conforms a gene pair with a transcriptional regulator, being required byB. abortusto escape from phagolysosomes, to achieve the endoplasmic reticulum and replicate within macrophages. Its deletion fromB. abortusstimulated the macrophages, which produced higher levels of pro-inflammatory cytokines and co-stimulatory proteins. This pathogen showed a reduced ability to adapt and grow under acidic conditions, which would negatively affect its escape from phagolysosomes and consequently, stimulating macrophages. Therefore, this work describes how this Zinc-dependent metalloproteinase significantly contributes in the intracellular adaptation ofB. abortus2308 in macrophages.
Development and validation of a real-time RT-PCR test for screening pepper and tomato seed lots for the presence of pospiviroids
Authors: Botermans Marleen , Roenhorst Johanna W. , Hooftman Marinus , Verhoeven Jacobus Th.J. , Metz Eveline , van Veen Esther J. , Geraats Bart P.J. , Kemper Mark , Beugelsdijk Debora C.M. , Koenraadt Harrie , Jodlowska Agata , Westenberg Marcel 
Published: April 2020

AbstractPotato spindle tuber viroid and other pospiviroids can cause serious diseases in potato and tomato crops. Consequently, pospiviroids are regulated in several countries. Since seed transmission is considered as a pathway for the introduction and spread of pospiviroids, some countries demand for the testing of seed lots of solanaceous crops for the presence of pospiviroids. A real-time RT-PCR test, named PospiSense, was developed for testing pepper (Capsicum annuum) and tomato (Solanum lycopersicum) seeds for seven pospiviroid species known to occur naturally in these crops. The test consists of two multiplex reactions running in parallel, PospiSense 1 and PospiSense 2, that target Citrus exocortis viroid (CEVd), Columnea latent viroid (CLVd), pepper chat fruit viroid (PCFVd), potato spindle tuber viroid (PSTVd), tomato apical stunt viroid (TASVd), tomato chlorotic dwarf viroid (TCDVd) and tomato planta macho viroid (TPMVd, including the former Mexican papita viroid). Dahlia latent viroid (DLVd) is used as an internal isolation control. Validation of the test showed that for both pepper and tomato seeds the current requirements of a routine screening test are fulfilled, i.e. the ability to detect one infested seed in a sample of c.1000 seeds for each of these seven pospiviroids. Additionally, the Pospisense test performed well in an inter-laboratory comparison, which included two routine seed-testing laboratories, and as such provides a relatively easy alternative to the currently used tests.
Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication
Authors: Puhach Olha , Ostermann Eleonore , Krisp Christoph , Frascaroli Giada , Schlüter Hartmut , Brinkmann Melanie M. , Brune Wolfram 
Published: April 2020

AbstractCytomegaloviruses (CMV) infect many different cell types and tissues in their respective hosts. Monocytes and macrophages play an important role in CMV dissemination from the site of infection to target organs. Moreover, macrophages are specialized in pathogen sensing and respond to infection by secreting cytokines and interferons. In murine cytomegalovirus (MCMV), a model for human cytomegalovirus, several genes required for efficient replication in macrophages have been identified, but their specific functions remain poorly understood. Here we show that MCMV m139, a gene of the conserved US22 gene family, encodes a protein that interacts with the DEAD box helicase DDX3, a protein involved in pathogen sensing and interferon (IFN) induction, and the E3 ubiquitin ligase UBR5. DDX3 and UBR5 also participate in the transcription, processing, and translation of a subset of cellular mRNAs. We show that m139 inhibits DDX3-mediated IFN-β induction and is necessary for efficient viral replication in bone-marrow derived macrophages. In vivo, m139 is crucial for viral dissemination to local lymph nodes and to the salivary glands. An m139-deficient MCMV also replicated to lower titers in SVEC4-10 endothelial cells. This replication defect was not accompanied by increased IFN-β transcription, but was rescued by knockout of either DDX3 or UBR5. Moreover, m139 co-localized with DDX3 and UBR5 in viral replication compartments in the cell nucleus. These results suggest that m139 inhibits DDX3-mediated IFN-β production in macrophages and antagonizes DDX3 and UBR5-dependent functions related to RNA metabolism in endothelial cells.Author SummaryHuman cytomegalovirus is an opportunistic pathogen that causes severe infections in immunocompromised individuals. The virus infects certain types, such as macrophages and endothelial cells, to ensure its dissemination within the body. Little is known about the viral factors that promote a productive infection of these cell types. The identification of critical viral factors and the molecular pathways they target can lead to the development of novel antiviral treatment strategies. Using the mouse cytomegalovirus as a model, we studied the viral m139 gene, which is important for virus replication in macrophages and endothelial cells and for dissemination in the mouse. This gene encodes a protein that interacts with the host proteins DDX3 and UBR5. Both proteins are involved in gene expression, and the RNA helicase DDX3 also participates in mounting an innate antiviral response. By interacting with DDX3 and UBR5, m139 ensures efficient viral replication in endothelial cells. Importantly, we identify m139 as a new viral DDX3 inhibitor, which curtails the production of interferon in macrophages.
The aggregate effect of implementation strength of family planning programs on modern contraceptive use at the health systems level in rural Malawi
Authors: Pattnaik Anooj , Mohan Diwakar , Tsui Amy , Chipokosa Sam , Katengeza Hans , Ndawala Jameson , Marx Melissa A. 
Published: April 2020

AbstractBackgroundTo explore the association between the strength of implementation of family planning (FP) programs on the use of modern contraceptives. Specifically, how strongly these programs are being implemented across a health facility’s catchment area in Malawi and the odds of a woman in that catchment area is using modern contraceptives. This information can be used to assess whether the combined impact of multiple large-scale FP programs is leading to change in the health outcomes they aim to improve.Methods and findingsWe used data from the 2017 Implementation Strength Assessment (ISA) that quantified how much of family planning programs at the health facility and community health worker levels were being implemented across every district of Malawi. We used a summary measure developed in a previous study that employs quantitative methods to combine data across FP domains and health system levels. We tested the association of this summary measure for implementation strength with household data from the 2015 Malawi Demographic Health Survey (DHS). We found that areas with stronger implementation of FP programs had higher odds of women using modern contraceptives compared with areas with weaker implementation. The association of ISA with use of modern contraception was different by education, marital status, and geography. After controlling for these factors, we found that the adjusted odds of using a modern contraceptive was three times higher in catchment areas with high implementation strength compared to those with lower strength.ConclusionMetrics that summarize how strongly FP programs are being implemented were used to show a statistically significantly positive relationship between increasing implementation strength and higher rates of modern contraceptive use. Decisionmakers at the various levels of health authority can use this type of summary measure to better understand the combined impact of their diverse FP programming and inform future programmatic and policy decisions. The findings also reinforce the idea that having a well-supported and supplied cadre of community health workers supplementing FP provision at the health facility can be an important health systems mechanism, especially in rural settings and to target youth populations.