bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socio-behavioural characteristics and HIV: findings from a graphical modelling analysis of 29 sub-Saharan African countries
Authors: Baranczuk Zofia , Estill Janne , Blough Sara , Meier Sonja , Merzouki Aziza , Maathuis Marloes H. , Keiser Olivia 
Published: April 2019

AbstractIntroductionSocio-behavioural factors may contribute to the wide variance in HIV prevalence between and within sub-Saharan African (SSA) countries. We studied the associations between socio-behavioural variables potentially related to the risk of acquiring HIV.MethodsWe used Bayesian network models to study associations between socio-behavioural variables that may be related to HIV. A Bayesian network consists of nodes representing variables, and edges representing the conditional dependencies between variables. We analysed data from Demographic and Health Surveys conducted in 29 SSA countries between 2010 and 2016. We predefined and dichotomized twelve variables, including factors related to age, literacy, HIV knowledge, HIV testing, domestic violence, sexual activity, and women’s empowerment. We analysed data on men and women for each country separately and then summarised the results across the countries. We conducted a second analysis including also the individual HIV status in a subset of 23 countries where this information was available. We presented summary graphs showing associations that were present in at least six countries (five in the analysis with HIV status).ResultsWe analysed data from 190,273 men (range across countries 2,295–17,359) and 420,198 women (6,621–38,948). The two variables with the highest total number of edges in the summary graphs were literacy and rural/urban location. Literacy was negatively associated with false beliefs about AIDS and, for women, early sexual initiation, in most countries. Literacy was also positively associated with ever being tested for HIV and the belief that women have the right to ask their husband to use condoms if he has a sexually transmitted infection. Rural location was positively associated with false beliefs about HIV and the belief that beating one’s wife is justified, and negatively associated with having been tested for HIV. In the analysis including HIV status, being HIV positive was associated with female-headed household, older age and rural location among women, and with no variables among men.ConclusionsLiteracy and urbanity were strongly associated with several factors that are important for HIV acquisition. Since literacy is one of the few variables that can be improved by interventions, this makes it a promising intervention target.
Widespread Sexual Dimorphism in the Transcriptome of Human Airway Epithelium in Response to Smoking
Authors: Yang Chen Xi , Shi Henry , Ding Irving , Yang Cheng Wei Tony , Kim Edward Kyoo-Hoon , Hackett Tillie-Louise , Leung Janice , Sin Don D. , Obeidat Ma’en 
Published: April 2019

ABSTRACTEpidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females at baseline and in response to smoking. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n=68; current smokers n=143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules’ level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosomes. The two modules were enriched in autophagy (up-regulated in female smokers) and response to virus and type 1 interferon signaling pathways which were down-regulated in female smokers compared to males. The results offer insights into the molecular mechanisms of the sexually dimorphic COPD risk and presentation potentially enabling a precision medicine approach to COPD.
Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax
Authors: Ayala Mario J.C. , Villela Daniel A.M. 
Published: April 2019

AbstractThe spread of drug resistance of Plasmodium falciparum and Plasmodium vivax parasites is a challenge towards malaria elimination.P. falciparum has shown an early and severe drug resistance in comparison to P. vivax in various countries. In fact, these Plasmodium species differ in their life cycle and treatment in various factors: development and duration of sexual parasite forms differ, symptoms severity are unequal, relapses present only in P. vivax cases, and the Artemisinin-based combination therapy (ACT) is only mandatory in all P. falciparum cases. We compared the spread of drug resistance for both species through two compartmental models using ordinary differential equations. The model structure describes how sensitive and resistant parasite strains infect a human population treated with antimalarials. We found that the early transmission before treatment and the low effectiveness of drug coverage support the prevalence of sensitive parasites delaying the emergence of resistant P. vivax. These results imply that earlier attention of symptomatic and reservoirs of P. vivax accelerates the spread of drug resistance as P. falciparum.
PyMethylProcess - highly parallelized preprocessing for DNA methylation array data
Authors: Levy Joshua J. , Titus Alexander J. , Salas Lucas A. , Christensen Brock C. 
Published: April 2019

AbstractSummaryThe ability to perform high-throughput preprocessing of methylation array data is essential in large scale methylation studies. While R is a convenient language for methylation analyses, performing highly parallelized preprocessing using Python can accelerate data preparation for downstream methylation analyses, including large scale production-ready machine learning pipelines. Here, we present a methylation data preprocessing pipeline called PyMethylProcess that is highly reproducible, scalable, and that can be quickly set-up and deployed through Docker and PIP.Availability and ImplementationProject Name: PyMethylProcessProject Home Page:https://github.com/Christensen-Lab-Dartmouth/PyMethylProcess. Available on PyPI aspymethylprocess.Available on DockerHub viajoshualevy44/pymethylprocess.Help Documentation:https://christensen-lab-dartmouth.github.io/PyMethylProcess/Operating Systems: Linux, MacOS, Windows (Docker)Programming Language: Python, ROther Requirements: Python 3.6, R 3.5.1, Docker (optional) License: MITContactjoshua.j.levy.gr@dartmouth.edu
Toxoplasma gondii in house mice Mus musculus domesticus from Dakar, Senegal: clues for oral rather than vertical mode of infection
Authors: Galal Lokman , Stragier Claire , Boumediène Farid , Hamidović Azra , Maugrion Océane , Dardé Marie-Laure , Brouat Carine , Mercier Aurélien 
Published: April 2019

AbstractToxoplasma gondii is an ubiquitous highly prevalent zoonotic protozoan. Cats are the definitive hosts, while all other warm-blooded animals are intermediate hosts for this parasite. Commensal rodents, being the main preys of cats, are probably the major reservoir for T. gondii. Rodents often develop dormant tissue cysts after ingestion of oocysts shed in the environment by cats in the form of contaminated feces. Experimental evidence that vertical transmission can be sufficient to the perpetuation of transmission between generations of mice has also been found. In natural settings, the relative epidemiological importance of vertical transmission over oral transmission is a matter of debate and raises the question of the possibility of a T. gondii cycle in the absence of cats. In the present study, we took advantage of an extensive survey of commensal rodents in Dakar, Senegal, where the house mouse Mus musculus domesticus is the predominant putative reservoir of T. gondii. Host genotype and spatial location through GPS referencing of all trapping localizations were investigated in relation to T. gondii infection in 12 sites of the city of Dakar and on Goree Island. In each sampled site, the occurrence of over-prevalence zones of T. gondii infection was investigated through Kulldorf’s statistic using SaTScan software. For the sites where a possible over-prevalence zone was identified, mice family lines were inferred from Discriminant Analysis of Principal Components (DAPC). In 3 of the 4 identified possible over-prevalence zones, T. gondii infection was not confined to a single family line, which suggested no association between kinship and infection occurrence. This finding rather suggests an environmental source of infection for mice associated with localized putative foci of environmental contamination and supports an oral route of infection for mice from Dakar rather than a cycle based on vertical transmission.
Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation
Authors: Morjaria Sejal , Schluter Jonas , Taylor Bradford P. , Littmann Eric R. , Carter Rebecca A. , Fontana Emily , Peled Jonathan U. , van den Brink Marcel R.M. , Xavier Joao B. , Taur Ying 
Published: April 2019

AbstractBackgroundDramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high-resolution through daily stool sampling and assess the impact of individual antibiotics on those changes.MethodsWe collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multi-parallel 16S rRNA gene sequencing, as well as density of bacteria in stool by qPCR. We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics.ResultsThe greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes.ConclusionsOur approach of daily sampling, bacterial density determination and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.
Deep Learning of Markov Model Based Machines for Determination of Better Treatment Option Decisions for Infertile Women
Authors: Srinivasa Rao Arni S.R. , Diamond Michael P. 
Published: April 2019

AbstractIn this technical article, we are proposing ideas those we have been developing of how machine learning and deep learning techniques can potentially assist obstetricians / gynecologists in better clinical decision making using infertile women in their treatment options in combination with mathematical modeling in pregnant women as examples.
Hypotonic stress induces fast, reversible degradation of the vimentin cytoskeleton via intracellular calcium release
Authors: Pan Leiting , Zhang Ping , Hu Fen , Yan Rui , He Manni , Li Wan , Xu Jingjun , Xu Ke 
Published: April 2019

SUMMARYThe dynamic response of the cell to osmotic changes is critical to its physiology and has been widely exploited for cell manipulation. Using 3D-STORM super-resolution microscopy, here we examine the hypotonic stress-induced ultrastructural changes of the cytoskeleton of a common fibroblast cell type. Unexpectedly, we observe a fast, yet reversible dissolution of the vimentin intermediate filament system that precedes ultrastructural changes of the supposedly more dynamic actin and tubulin cytoskeletal systems, as well as changes in cell morphology. In combination with calcium imaging and biochemical analysis, we next show that the vimentin-specific fast cytoskeletal degradation under hypotonic stress is due to proteolysis by the calcium-dependent protease calpain. We find the process to be activated by the hypotonic stress-induced calcium release from intracellular stores, and so is efficiently suppressed by inhibiting any part of the IP3-Ca2+-calpain pathway we establish. Together, our findings highlight an unexpected, fast degradation mechanism for the vimentin cytoskeleton in response to the external stimuli, and point to the significant, yet previously overlooked physiological impacts of hypotonic stress-induced intracellular calcium release on cell ultrastructure and function.
Crippling the bacterial cell wall molecular machinery
Authors: Williams Allison H. , Wheeler Richard , Deghmane Ala-Eddine , Santecchia Ignacio , Impens Francis , Bastos Paulo André Dias , Hicham Samia , Nilges Maryse Moya , Malosse Christian , Chamot-Rooke Julia , Haouz Ahmed , Robins William P. , Taha Muhamed-Kheir , Boneca Ivo Gomperts 
Published: April 2019

AbstractLytic transglycosylases (LT) are redundant enzymes that play a critical role in peptidoglycan (PG) recycling and metabolism. LT(s) role in cell wall-modifying complexes and usefulness as antimicrobial drug targets remain elusive. We determined at high-resolution a structure of the membrane-bound homolog of the soluble LT fromNeisseriaspecies with a disordered active site helix (alpha helix 30). Alpha helix 30 is crucial for binding PG during catalysis1. Here we show using an alpha helix 30 deletion strain that LT (LtgA) determines the integrity of the cell wall, participates in cell division and separation, and can be manipulated to impair the fitness of the human pathogenNeisseria meningitidisduring infection. Characterization ofltgAhelix deleted strain interactome identified glycan chain remodeling enzymes whose function appear to be modulated by LTs. Targeting LTs can disrupt the PG machinery, which is fatal for the bacterium, a new approach for antibiotic development.
An electrophysiological approach to measure changes in the membrane surface potential in real time
Authors: Burtscher Verena , Hotka Matej , Freissmuth Michael , Sandtner Walter 
Published: April 2019

AbstractBiological membranes carry fixed charges at their surfaces. These arise primarily from phospholipid head groups. In addition, membrane proteins contribute to the surface potential with their charged residues. Membrane lipids are asymmetrically distributed. Because of this asymmetry the net negative charge at the inner leaflet exceeds that at the outer leaflet. Changes in surface potential are predicted to shape the capacitive properties of the membrane (i.e. the ability of the membrane to store electrical charges). Here, we show that it is possible to detect changes in surface potential by an electrophysiological approach: the analysis of cellular currents relies on assuming that the electrical properties of a cell are faithfully described by a three-element circuit - i.e. the minimal equivalent circuit - comprised of two resistors and one capacitor. However, to account for changes in surface potential it is necessary to add a battery to this circuit connected in series with the capacitor. This extended circuit model predicts that the current response to a square-wave voltage pulse harbors information, which allows for separating the changes in surface potential from a true capacitance change. We interrogated our model by investigating changes in capacitance induced by ligand binding to the serotonin transporter (SERT) and to the glycine transporters (GlyT1 and GlyT2). The experimental observations were consistent with the predictions of the extended circuit. We conclude that ligand-induced changes in surface potential (reflecting the binding event) and in true membrane capacitance (reflecting the concomitant conformational change) can be detected in real time even in instances where they occur simultaneously.Statement of SignificanceThe plasma membrane of a cell possesses fixed charges on both surfaces. Surface charges play an important role in many biological processes. However, the mechanisms, which regulate the surface charge densities at the plasma membrane, are poorly understood. This is in part due to lack of experimental approaches that allow for detecting changes in surface charges in real time. Here, we show that it is possible to track alterations in the electric potential at the membrane surface with high temporal resolution by an electrophysiological approach. Importantly, the described method allows for discriminating between a change in surface potential and a change in true membrane capacitance (e.g. a change in membrane area), even if these occur in parallel.
Slc7a11 modulated by POU2F1 is involved in pigmentation in rabbit
Authors: Chen Yang , Hu Shuaishuai , Mu Lin , Zhao Bohao , Wang Manman , Yang Naisu , Bao Guolian , Zhu Cigen , Wu Xinsheng 
Published: April 2019

AbstractSolute carrier family 7 member 11 (Slc7a11) codes for a cystine/glutamate xCT transporter and can control production of pheomelanin pigment to change fur and skin colors of animals. Previous studies found that the skin expression levels of Slc7a11 varied significantly with the fur colors of the Rex Rabbit. However, it is not yet known the molecular regulation mechanism of Slc7a11 in pigmentation. Here rabbit melanocytes were first isolated and identified. The distribution and expression pattern of Slc7a11 was confirmed in rabbit skin with different fur colors. Slc7a11 could affect the expression of pigmentation related genes and thus affect melanogenesis. Meanwhile, Slc7a11 decreased melanocytes apoptosis, but inhibition of Slc7a11 enhanced apoptosis. Furthermore, it was found that POU2F1 protein bound to the -713 to -703 bp region of Slc7a11 promoter to inhibite its activity by dual-luciferase reporter and site-directed mutagenesis assay. This study uncover the function of the Slc7a11 in melanogenesis and provided in-depth analysis of the mechanism of fur pigmentation.
Daedalus and Gasz recruit Armitage to mitochondria, bringing piRNA precursors to the biogenesis machinery
Authors: Munafò Marzia , Manelli Vera , Falconio Federica A. , Sawle Ashley , Kneuss Emma , Eastwood Evelyn L. , Seah Jun Wen Eugene , Czech Benjamin , Hannon Gregory J. 
Published: April 2019

ABSTRACTThe piRNA pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialised machinery that converts long single-stranded precursors into small RNAs of ~25-nucleotides in length. This process involves factors that operate in two different subcellular compartments: the nuage/Yb-body and mitochondria. How these two sites communicate to achieve accurate substrate selection and efficient processing remains unclear. Here, we investigate a previously uncharacterized piRNA biogenesis factor, Daedalus (Daed), that is located on the outer mitochondrial membrane. Daed is essential for Zucchini-mediated piRNA production and for the correct localisation of the indispensable piRNA biogenesis factor, Armitage (Armi). We find that Gasz and Daed interact with each other and likely provide a mitochondrial “anchoring platform” to ensure that Armi is held in place, proximal to Zucchini, during piRNA processing. Our data suggest that Armi initially identifies piRNA precursors in nuage/Yb-bodies in a manner that depends upon Piwi and then moves to mitochondria to present precursors to the mitochondrial biogenesis machinery. These results represent a significant step in understanding a critical aspect of transposon silencing, namely how RNAs are chosen to instruct the piRNA machinery in the nature of its silencing targets.
Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton
Authors: Zhou Wenqing , Hsu Alan Y. , Wang Yueyang , Wang Tianqi , Jeffries Jacob , Wang Xu , Mohammad Haroon , Seleem Mohamed N. , Umulis David , Deng Qing 
Published: April 2019

AbstractNeutrophils rely on glycolysis for energy production. How mitochondria regulate neutrophil function is not fully understood. Here, we report that mitochondrial outer membrane protein Mitofusin 2 (Mfn2) regulates neutrophil homeostasis in vivo. Mfn2-deficient neutrophils are released from the hematopoietic tissue and trapped in the vasculature in zebrafish embryos. Human neutrophil-like cells deficient with MFN2 fail to arrest on activated endothelium under sheer stress or perform chemotaxis. Deletion of Mfn2 results in a significant reduction of neutrophil infiltration to the inflamed peritoneal cavity in mice. Mfn2, but not Mfn1, -null mouse embryonic fibroblast cells have altered actin structure and are impaired in wound closure. MFN2-deficient neutrophil-like cells display heightened intracellular calcium levels and Rac activation after chemokine stimulation. Mechanistically, MFN2 maintains mitochondria-ER interaction. Restoring mitochondria-ER tether rescues the chemotaxis defect and Rac activation resulted from MFN2 depletion. Finally, inhibition of Rac restores chemotaxis in MFN2-deficient neutrophils. Altogether, we identified that MFN2 regulates neutrophil migration via suppressing Rac activation and uncovered a previously unrecognized role of MFN2 in regulating the actin cytoskeleton.
How delayed treatment benefits and harms would impact the optimal timing of statin initiation for cardiovascular primary prevention
Authors: Hayward Rodney A. , Schell Greggory , Robinson Jennifer G. , Sussman Jeremy B. , Lavieri Mariel S. 
Published: April 2019

AbstractBackgroundGenetic studies suggest that the relative risk reduction (RRR) of statins may increase over time, potentially resulting in much greater long-term benefit if statins are started before cardiovascular (CV) risk is high.MethodsWe used a nationally representative sample of American adults to estimate effects of initiating a statin when 10-year CV risk reaches 5%, 10% or 15%. We examined scenarios in which a statin’s initial RRR (30%) gradually doubles over 10 to 30 years of treatment.ResultsInitiating a statin when 10-year CV risk is 5% resulted in a mean of 20.1 years on a statin before age 75 (8 years more than starting when CV risk reaches 10%). If a statin’s RRR doubles over 20 years, starting when CV risk is 5% would save about 5.1 to 6.1 additional QALYs per 1000 additional treatment years than starting when CV risk is 10%. Most of this additional benefit was accrued by those who reach a 5% risk at a younger age. Due to the prolonged treatment period, however, early treatment could also result in net harm if the treatment slowly increased a major complication of aging, such as muscular or neurological aging.ConclusionsIn a thought experiment exploring the impact of delayed effects, we found that if the relative effectiveness of statin therapy gradually doubles over a 10 to 30 year period, starting a statin when 10-year CV risk is 5% could have much more long-term benefit than starting a statin when CV risk is 10%. Most of the additional benefit occurred in those at elevated age-adjusted CV risk. Unfortunately, given the long duration of treatment, substantial delayed statin harms, if present, could outweigh these potential benefits and result in substantial net harm.