bluuebunny/crossref_metadata_2025_split huggingface dataset:
mity: A highly sensitive mitochondrial variant analysis pipeline for whole genome sequencing data
Authors: Puttick Clare , Kumar Kishore R , Davis Ryan L , Pinese Mark , Thomas David M , Dinger Marcel E , Sue Carolyn M , Cowley Mark J 
Published: November 2019

AbstractMotivationMitochondrial diseases (MDs) are the most common group of inherited metabolic disorders and are often challenging to diagnose due to extensive genotype-phenotype heterogeneity. MDs are caused by mutations in the nuclear or mitochondrial genome, where pathogenic mitochondrial variants are usually heteroplasmic and typically at much lower allelic fraction in the blood than affected tissues. Both genomes can now be readily analysed using unbiased whole genome sequencing (WGS), but most nuclear variant detection methods fail to detect low heteroplasmy variants in the mitochondrial genome.ResultsWe present mity, a bioinformatics pipeline for detecting and interpreting heteroplasmic SNVs and INDELs in the mitochondrial genome using WGS data. In 2,980 healthy controls, we observed on average 3,166× coverage in the mitochondrial genome using WGS from blood. mity utilises this high depth to detect pathogenic mitochondrial variants, even at low heteroplasmy. mity enables easy interpretation of mitochondrial variants and can be incorporated into existing diagnostic WGS pipelines. This could simplify the diagnostic pathway, avoid invasive tissue biopsies and increase the diagnostic rate for MDs and other conditions caused by impaired mitochondrial function.Availabilitymity is available from https://github.com/KCCG/mityunder an MIT license.Contactclare.puttick@crick.ac.uk, carolyn.sue@sydney.edu.au, MCowley@ccia.org.au
Large-scale transgenicDrosophilaresource collections for loss- and gain-of-function studies
Authors: Zirin Jonathan , Hu Yanhui , Liu Luping , Yang-Zhou Donghui , Colbeth Ryan , Yan Dong , Ewen-Campen Ben , Tao Rong , Vogt Eric , VanNest Sara , Cavers Cooper , Villalta Christians , Comjean Aram , Sun Jin , Wang Xia , Jia Yu , Zhu Ruibao , Peng Pin , Yu Jinchao , Shen Da , Qiu Yuhao , Ayisi Limmond , Ragoowansi Henna , Fenton Ethan , Efrem Senait , Parks Annette , Saito Kuniaki , Kondo Shu , Perkins Liz , Mohr Stephanie E. , Ni Jianquan , Perrimon Norbert 
Published: November 2019

ABSTRACTThe Transgenic RNAi Project (TRiP), aDrosophilafunctional genomics platform at Harvard Medical School, was initiated in 2008 to generate and distribute a genome-scale collection of RNAi fly stocks. To date, the TRiP has generated >15,000 RNAi fly stocks. As this covers mostDrosophilagenes, we have largely transitioned to development of new resources based on CRISPR technology. Here, we present an update on our libraries of publicly available RNAi and CRISPR fly stocks, and focus on the TRiP-CRISPR overexpression (TRiP-OE) and TRiP-CRISPR knockout (TRiP-KO) collections. TRiP-OE stocks express sgRNAs targeting upstream of a gene transcription start site. Gene activation is triggered by co-expression of catalytically dead Cas9 (dCas9) fused to an activator domain, either VP64-p65-Rta (VPR) or Synergistic Activation Mediator (SAM). TRiP-KO stocks express one or two sgRNAs targeting the coding sequence of a gene or genes, allowing for generation of indels in both germline and somatic tissue. To date, we have generated more than 5,000 CRISPR-OE or -KO stocks for the community. These resources provide versatile, transformative tools for gene activation, gene repression, and genome engineering.
Improved inference and prediction of bacterial genotype-phenotype associations using pangenome-spanning regressions
Authors: Lees John A. , Tien Mai T. , Galardini Marco , Wheeler Nicole E. , Corander Jukka 
Published: November 2019

ABSTRACTDiscovery of influential genetic variants and prediction of phenotypes such as antibiotic resistance are becoming routine tasks in bacterial genomics. Genome-wide association study (GWAS) methods can be applied to study bacterial populations, with a particular emphasis on alignment-free approaches, which are necessitated by the more plastic nature of bacterial genomes. Here we advance bacterial GWAS by introducing a computationally scalable joint modeling framework, where genetic variants covering the entire pangenome are compactly represented by unitigs, and the model fitting is achieved using elastic net penalization. In contrast to current leading GWAS approaches, which test each genotype-phenotype association separately for each variant, our joint modelling approach is shown to lead to increased statistical power while maintaining control of the false positive rate. Our inference procedure also delivers an estimate of the narrow-sense heritability, which is gaining considerable interest in studies of bacteria. Using an extensive set of state-of-the-art bacterial population genomic datasets we demonstrate that our approach performs accurate phenotype prediction, comparable to popular machine learning methods, while retaining both interpretability and computational efficiency. We expect that these advances will pave the way for the next generation of high-powered association and prediction studies for an increasing number of bacterial species.
De novo identification of toxicants that cause irreparable damage to parasitic nematode intestinal cells
Authors: Jasmer Douglas P. , Rosa Bruce A. , Tyagi Rahul , Bulman Christina A. , Beerntsen Brenda , Urban Joseph F. , Sakanari Judy , Mitreva Makedonka 
Published: November 2019

AbstractEfforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, a novel approach focused on integrating a pan-Nematoda multi-omics data targeted to a specific nematode organ system (the intestinal tract) with evidence-based filtering and chemogenomic screening was undertaken. Based onde novocomputational target prioritization of the 3,564 conserved intestine genes inA. suum, exocytosis was identified as a high priority pathway, and predicted inhibitors of exocytosis were tested using the large roundworm (Ascaris suumlarval stages), a filarial worm (Brugia pahangiadult and L3), a whipworm (Trichuris murisadult), and the non-parasitic nematodeCaenorhabditis elegans. 10 of 13 inhibitors were found to cause rapid immotility inA. suumL3 larvae, and five inhibitors were effective against the three phylogenetically diverse parasitic nematode species, indicating potential for a broad spectrum anthelmintics. Several distinct pathologic phenotypes were resolved related to molting, motility, or intestinal cell and tissue damage using conventional and novel histologic methods. Pathologic profiles characteristic for each inhibitor will guide future research to uncover mechanisms of the anthelmintic effects and improve on drug designs. This progress firmly validates the focus on intestinal cell biology as a useful resource to develop novel anthelmintic strategies.Author summaryThe intestinal cells of parasitic nematodes are not known to regenerate, therefore disruption of essential processes that cause irreparable damage to intestinal cells is expected to promote worm expulsion. To facilitate improved methods of therapy we need to better understand the basic intestinal cell and tissue functions of this critical organ. To that end have undertaken a comprehensive analysis of multi-omics omics data and identify and prioritize intestinal genes/pathways with essential functions and associated drugs and established a foundational model of the STH intestinal system using the large roundwormAscaris suumto test and validate inhibitors of these functions. We found 10 inhibitors to impacted motility, and seven of those showed severe pathology and an apparent irreparable damage to intestinal cells. Furthermore, five inhibitors were effective against the three phylogenetically diverse parasitic nematode species, indicating potential for a broad spectrum anthelmintics. Our results firmly validate the focus on intestinal cell biology as a useful resource to develop novel anthelmintic strategies.
Confirmation of local transmission of Orientia tsutsugamushi during scrub typhus outbreaks in Nepal
Authors: Dhimal Meghnath , Dumre Shyam Prakhas , Sharma Guna Niddhi , Khanal Pratik , Ranabhat Kamal , Shah Lalan Prasad , Lal Bibek Kumar , Jha Runa , Upadhyaya Bishnu Prasad , Acharya Bhim , Shrestha Sanjaya Kumar , Davidson Silas A. , Charoensinphon Piyada , Karki Khem B. 
Published: November 2019

ABSTRACTBackgroundScrub typhus is a severely ignored tropical disease and a leading cause of undifferentiated febrile illness worldwide caused by infection of an obligate intracellular bacteria Orientia tsutsugamushi. It has been rapidly expanding in South Asian countries, although clear epidemiological information is not available from Nepal. After the 2015 earthquake in Nepal, a sudden upsurge in scrub typhus cases was reported. The objective of this study was to investigate scrub typhus and its causative agents in human, rodent and chigger mites to better understand the ongoing transmission ecology.MethodsScrub typhus cases with confirmed diagnosis throughout the country were included in the analysis. Studies were concentrated in the Chitwan district, the site of a major outbreak in 2016. Additional country-wide data from 2015 to 2017 was made available from the government database to analyse the disease distribution using geographical mapping.ResultsDuring 2015-2017, 1,239 scrub typhus cases were confirmed with the largest outbreak occurring in 2016 with 831 (67.1%) cases. The remainder 267 cases were reported in 2017. The case fatality rate was 5.7% in 2015 and declined to 1.1% in 2017. Nationwide outbreak of scrub typhus was identified as the cases were found from 52 of the 75 districts of Nepal. A seasonal trend was observed with a peak during August and September (p = 0.01). In addition to the human cases, the presence of O. tsutsugamushi was also confirmed in rodents and chigger mites from the outbreak areas of southern Nepal.ConclusionThe detection of O. tsutsugamushi in human, rodent, and chigger mites from outbreak locations and wide-spread reports of scrub typhus throughout the country over two years confirms the ongoing transmission of O. tsutsugamushi with a firmly established ecology in Nepal. The country’s health system needs to be strengthened for systematic surveillance, early outbreaks detection, and immediate response actions including treatment and preventive measures.Author SummaryScrub typhus is a disease caused by a bacteria called Orientia tsutsugamushi and transmitted to people through bites of infected chiggers (larval mites). After the 2015 Gorkha earthquake in Nepal, a sudden upsurge in scrub typhus cases was reported with repeated outbreaks from different parts of the country. This study has documted epidemiology of scrub typhus and its causative agents in human, rodent and chigger mites confimring the local transmission O. tsutsugamushi with a firmly established ecology in Nepal. The local transmission of the diseases from most parts of the country demands strengthening for systematic surveillance, early outbreaks detection, and immediate response actions including treatment and preventive measures.
High Prevalence of Strongyloidiasis in Spain: A Hospital-Based Study
Authors: Requena-Méndez Ana , Salas-Coronas Joaquin , Salvador Fernando , Gomez-Junyent Joan , Villar-Garcia Judith , Santin Miguel , Muñoz Carme , Gonzalez-Cordon Ana , Cabezas Fernández Maria Teresa , Sulleiro Elena , del Mar Arenas Maria , Somoza Dolors , Vazquez-Villegas Jose , Treviño Begoña , Rodríguez Esperanza , Valls Maria Eugenia , Subirá Carme , Muñoz Jose ,   on behalf of the STRONG-SEMTSI working group
Published: November 2019

AbstractStrongyloidiasis is a prevailing helminth infection ubiquitous in tropical and subtropical areas. However, prevalence data are scarce in migrant populations.This study aims at evaluating the prevalence of S. stercoralis at hospital level in migrant populations or long term travellers being attended in out-patient and in-patient units as part of a systematic screening implemented in 6 Spanish hospitals. A cross-sectional study was conducted and systematic screening for S. stercoralis infection using serological tests was offered to all eligible participants. The overall seroprevalence of S. stercoralis was 9.04% (95% confidence interval [95%CI] 7.76 −10.31). The seroprevalence of people with a risk of infection acquired in Africa and Latin America was 9.35% (95%CI 7.01-11.69), 9.22% (7.5-10.93), respectively. The number of individuals coming from Asian countries was significantly smaller and the overall prevalence in these countries was 2.9% (95%CI −0.3; −6.2). There was only one case (1/14 (7.14%) from an individual from East European countries. The seroprevalence in units attending potentially immunosuppressed patients was significantly lower (5.64%) compared with the seroprevalence in other units of the hospital (10.20%) or Tropical diseases units (13.33%) (p<0.001). Conclusions: We report a hospital-based systematic screening of strongyloidiasis with a seroprevalence of almost 10% in a mobile population coming from endemic areas suggesting the need of implementing strongyloidiasis screening in hospitalized patients coming from endemic areas, particularly if they are at risk of immunosuppression.Author summaryStrongyloidiasis is an infection caused by the helminth Strongyloides stercoralis which is ubiquitous in tropical and subtropical areas. In the rest of the countries, it is also frequent in migrants coming from tropical and subtropical areas. The disease is more severe when an infected subject has an impaired immune system. Within this study we have evaluated the prevalence of this infection in people being attended in six Spanish hospitals. The prevalence was around 9%, being higher in Africa and Latin America compared with other regions. In addition, the prevalence in patients with an impaired immune system (immunosuppression) was lower compared with people non suffering immunosuppression. These results suggest that the prevalence of strongyloidiasis is quite high among migrants living in Spain and that a screening programme should be designed, particularly in immunosuppressed patients that are at more risk of suffering severe complications of the infection.
Complementary Performances of Convolutional and Capsule Neural Networks on Classifying Microfluidic Images of Dividing Yeast Cells
Authors: Ghafari Mehran , Clark Justin , Guo Hao-Bo , Yu Ruofan , Sun Yu , Dang Weiwei , Qin Hong 
Published: November 2019

AbstractMicrofluidic-based assays have become effective high-throughput approaches to examining replicative aging of budding yeast cells. Deep learning may offer an efficient way to analyze a large number of images collected from microfluidic experiments. Here, we compare three deep learning architectures to classify microfluidic time-lapsed images of dividing yeast cells into categories that represent different stages in the yeast replicative aging process. We found that convolutional neural networks outperformed capsule networks in terms of accuracy, precision, and recall. The capsule networks had the most robust performance at detecting one specific category of cell images. An ensemble of three best-fitted single-architecture models achieves the highest overall accuracy, precision, and recall due to complementary performances. In addition, extending classification classes and augmentation of the training dataset can improve the predictions of the biological categories in our study. This work lays a useful framework for sophisticated deep-learning processing of microfluidics-based assays of yeast replicative aging.
CXCR4 and MIF are required for neutrophil extracellular trap release triggered byPlasmodium-infected erythrocytes
Authors: Rodrigues Danielle S. A. , Prestes Elisa B. , de Souza Silva Leandro , Pinheiro Ana Acácia S. , Ribeiro Jose Marcos C. , Dicko Alassane , Duffy Patrick E. , Fried Michal , Francischetti Ivo M. B. , Saraiva Elvira M. , Paula Neto Heitor A. , Bozza Marcelo T. 
Published: November 2019

AbstractNeutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show, similarly to previous reports, that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma. We used cultured erythrocytes and isolated human neutrophils to show thatPlasmodium-infected red blood cells release MIF, which in turn caused NET formation by neutrophils in a mechanism dependent on the C-X-C chemokine receptor type 4 (CXCR4). NET production was dependent on histone citrulination by PAD4 and independent of reactive oxygen species (ROS), myeloperoxidase (MPO) or NE. In vitro, NETs functioned to restrain parasite dissemination in a mechanism dependent on MPO and NE activities. Finally, C57/B6 mice infected withP. bergheiANKA, a well-established model of cerebral malaria, presented high amounts of circulating DNA, while treatment with DNAse increased parasitemia and accelerated mortality, indicating a role for NETs in resistance againstPlasmodiuminfection.Author summaryProtozoans of the Plasmodium genre infect red blood cells and cause malaria in humans and various other mammalian species. Estimated malaria cases are at more than 200 million, with 450,000 deaths per year, being cerebral malaria a serious complication that accounts for the majority of deaths. Neutrophils are cells that participate in host defense against pathogens. These cells use various mechanisms to kill invading microrganisms, including the release of webs of DNA, called neutrophil extracellular traps (NETs). These NETs can help control infections but can also induce tissue damage and their role in malaria and the mechanisms of NET production during malaria infection are starting to be understood. Here we show that infected red blood cells produce a cytokine, macrophage migration inhibitory factor (MIF) that stimulates neutrophils to release NETs. These NETs function to limitPlasmodiumdissemination and, thus, digestion of NETs with DNAse treatment causes increased parasitemia and accelerated death in an experimental model of cerebral malaria. Our study uncovers the mechanism by which infected red blood cells stimulate neutrophils to release NETs and suggest an important participation of this process in malaria control.
Bacteriophages can be used as infection control agents: A proof-of concept study involving anti-Acinetobacter baumannii phage
Authors: Hussain Aamir , Manzoor Amna , Ullah Ihsan , Aziz Atif , Aziz Mubashar , Saeed Muhammad Qamar 
Published: November 2019

AbstractHospital acquired infections are responsible for morbidity and mortality worldwide. Acinetobacter spp. infections are particularly notorious for complicating patient management in ICU settings. Extremely high mortality rates are associated with Acinetobacter infections because of their resistance to first- and second-line drugs. There is imminent need to develop infections control systems that are specific and environment friendly. Here, we report a proof-of-concept anti-Acinetobacter spp. bacteriophage-based infection control assay that is very target specific as well as innocuous to environment. extensively drug resistant (XDR) Acinetobacter baumannii strain was inoculated at various solid surfaces. A bacteriophage, enriched in the same strain, was applied on the inoculated surfaces. Phenol (carbolic acid) was used as a positive control. We show that bacteriophages can be used as infection control agents. In our assay, they killed XDR Acinetobacter baumannii present on solid surfaces. Our bacteriophage was extremely effective at reducing the CFU of inoculated strain to almost undetectable levels.
The heparan sulfate proteoglycan Syndecan-1 influences local bone cell communication via the RANKL/OPG axis
Authors: Timmen Melanie , Hidding Heriburg , Götte Martin , El Khassawna Thaqif , Kronenberg Daniel , Stange Richard 
Published: November 2019

AbstractThe heparan sulfate proteoglycan Syndecan-1, a mediator of signals between the extracellular matrix and cells involved is able to interact with OPG, one of the major regulators of osteoclastogenesis. The potential of osteoblasts to induce osteoclastogenesis is characterized by a switch of OPG (low osteoclastogenic potential) towards RANKL production (high osteoclastogenic potential).In the present study, we investigated the influence of endogenous Syndecan-1 on local bone-cell-communication via the RANKL/OPG-axis in murine osteoblasts and osteoclasts in wild type and Syndecan-1 lacking cells. Syndecan-1 expression and secretion was increased in osteoblasts with high osteoclastogenic potential. Syndecan-1 deficiency led to increased OPG release by osteoblasts that decreased the availability of RANKL. In co-cultures of Syndecan-1 deficient osteoblasts with osteoclast these increased OPG in supernatant caused decreased development of osteoclasts. Syndecan-1 and RANKL level were increased in serum of aged WT mice, whereas Syndecan-1 deficient mice showed high serum OPG concentration. However, bone structure of Syndecan-1 deficient mice was not different compared to wild type.In conclusion, Syndecan-1 could be regarded as a new modulator of bone-cell-communication via RANKL/OPG axis. This might be of high impact during bone regeneration or bone diseases like cancer where Syndecan-1 expression is known to be even more prevalent.