bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients
Authors: Kim Chanmi , Latif Iqra , Neupane Durga P. , Lee Gi Young , Kwon Ryan S. , Batool Alia , Ahmed Qasim , Qamar Muhammad Usman , Song Jeongmin 
Published: June 2021

AbstractSepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients to determine their antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and control strategies for XDR S. Typhi.
Detecting Flavobacterial Fish Pathogens in the Environment Using High-Throughput Community Analysis
Authors: Testerman Todd , Beka Lidia , McClure Emily Ann , Reichley Stephen R. , King Stacy , Welch Timothy J. , Graf Joerg 
Published: June 2021

AbstractDiseases caused by the fish pathogensFlavobacterium columnareandFlavobacterium psychrophilumare major contributors of preventable losses in the aquaculture industry. The persistent and difficult to control infections caused by these bacteria make timely intervention and prophylactic elimination of pathogen reservoirs important measures to combat these disease-causing agents. In the present study, we present two independent assays for detecting these pathogens in a range of environmental samples. Natural water samples were inoculated withF. columnareandF. psychrophilumcells, and pathogen levels were detected using Illumina MiSeq sequencing and droplet digital PCR. Both detection methods accurately identified pathogen-positive samples and showed good agreement in quantifying each pathogen. Additionally, the real-world application of these approaches was demonstrated using environmental samples collected at a rainbow trout aquaculture facility. These results show that both methods can serve as useful tools for surveillance efforts in aquaculture facilities, where the early detection of these flavobacterial pathogens may direct preventative measures to reduce disease occurrence.ImportanceEarly detection of a deadly disease outbreak in a population can be the difference between mass fatality or mitigated effects. In the present study, we evaluated and compared two techniques for detecting economically impactful aquaculture pathogens. We demonstrate that one of these techniques, 16S rRNA gene sequencing using Illumina MiSeq technology, provides the ability to accurately detect two fish pathogens,F. columnareandF. psychrophilum, while simultaneously profiling the native microbial community. The second technique, droplet digital PCR, is commonly used for pathogen detection, and the results obtained using the assays we designed with this method served to validate those obtained using the MiSeq method. These two methods offer distinct advantages. The MiSeq method pairs pathogen detection and microbial community profiling to answer immediate and long-term fish health concerns, while droplet digital PCR method provides fast and highly sensitive detection that is useful for surveillance and rapid clinical responses.
I will teach you here or there, I will try to teach you anywhere: perceived supports and barriers for emergency remote teaching during COVID-19 pandemic
Authors: Donham Cristine , Barron Hillary A. , Alkhouri Jourjina , Kumarath Maya Changaran , Alejandro Wesley , Menke Erik , Kranzfelder Petra 
Published: June 2021

ABSTRACTBackgroundDue to the COVID-19 pandemic, many universities moved to emergency remote teaching (ERT). This allowed institutions to continue their instruction despite not being in person. However, ERT is not without consequences. For example, students may have inadequate technological supports, such as reliable internet and computers. Students may also have poor learning environments at home and may need to find added employment to support their families. Additionally, there were consequences to faculty. It has been shown that female instructors are more disproportionately impacted in terms of mental health issues and increased domestic labor.This research aims to investigate instructors’ and students’ perceptions of their transition to ERT. Specifically, we wanted to:
Identify supports and barriers during the transition to ERTCompare instructors experiences with the student experiencesExplore these supports and barriers within the context of social presence, teaching presence, and/or cognitive presence during ERT as well as how these supports and barriers relate to scaffolding in emergency remote coursesDesignUsing grounded theory techniques, we applied two-cycle, qualitative analyses to assess the instructor transcripts. In first-cycle analysis, we used open coding to develop initial ideas from the data. We then used second cycle coding to generate categories with definitions and criteria agreed upon during discussion-based consensus building. Finally, these categories and descriptions were used to code student survey data.Analyses/InterpretationsInstructors identified twice as many barriers as supports in their teaching during the transition to ERT and identified casual and formal conversations with colleagues as valuable supports. Emerging categories for barriers consisted of academic integrity concerns as well as technological difficulties. Similarly, students identified more barriers than supports in their learning during the transition to ERT. More specifically, students described pre-existing course structure, classroom technology, and community as best supporting their learning. Barriers that challenged student learning included classroom environment, student availability, and student emotion and comfort.ContributionTogether, this research will help us understand supports and barriers to teaching and learning during the transition to ERT. This understanding can help us better plan and prepare for future emergencies, particularly at MSIs, where improved communication and increased access to resources for both students and instructors are key.
Constitutive IFNα protein production in bats
Authors: Bondet Vincent , Le Baut Maxime , Le Poder Sophie , Lécu Alexis , Petit Thierry , Wedlarski Rudy , Duffy Darragh , Le Roux Delphine 
Published: June 2021

AbstractBats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but was not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.
Molecular Determinants of Ligand Residence in Galectin
Authors: Koneru Jaya Krishna , Sinha Suman , Mondal Jagannath 
Published: June 2021

AbstractThe recognition of carbohydrates by lectins play key roles in diverse cellular processes such as cellular adhesion, proliferation and apoptosis which makes it a promising therapeutic target against cancers. One of the most functionally active lectins, galectin-3 is distinctively known for its specific binding affinity towards β-galactoside. Despite the prevalence of high-resolution crystallographic structures, the mechanistic basis and the molecular determinants of the sugar recognition process by galectin-3 are currently elusive. Here we address this question by capturing the complete dynamical binding process of human galectin-3 with its native ligand N-acetyllactosamine (LacNAc) and one of its synthetic derivatives by unbiased Molecular Dynamics simulation. In our simulations, both the natural ligand LacNAc and its synthetic derivative, initially solvated in water, diffuse around the protein and eventually recognise the designated binding site at the S-side of galectin-3, in crystallographic precision and identifies key metastable intermediate ligand-states around the galectin on their course to eventual binding. The simulations highlight that the origin of the experimentally observed multi-fold efficacy of synthetically designed ligand-derivative over its native natural ligand LacNAc lies in the derivative’s relatively longer residence time in the bound pocket. A kinetic analysis demonstrates that the LacNAc-derivative would be more resilient compared to the parent ligand against unbinding from the protein binding site. In particular, the analysis identifies that interactions of the binding pocket residues Trp181, Arg144 and Arg162 with the tetrafuorophenyl ring of the derivative as the key determinant for the synthetic ligand to latch into the pocket.Graphical Abstract
Natural history of Camponotus renggeri and Camponotus rufipes (Hymenoptera: Formicidae) in an Atlantic Forest reserve, Brazil
Authors: Pereira-Romeiro Miguel Piovesana , Vanin Gabriel Tofanelo , Azevedo-Silva Marianne , Mori Gustavo Maruyama 
Published: June 2021

AbstractWidespread species face a wide variety of environmental challenges and their morphology, behavior, and natural history may change across their range. However, not rarely, natural history research is restricted to one or few locations. That is the case for Camponotus renggeri and C. rufipes. Both species occur across South America in different ecosystems, but most research on these species is restricted to the Brazilian savanna, known as Cerrado. Here, we describe the foraging area, nesting habits, and activity schedule of C. renggeri and C. rufipes in an Atlantic Forest reserve in SE Brazil. C. renggeri foraged exclusively during nighttime and C. rufipes remained active throughout the day, but with little intensity during daylight hours. Most nests of both species were composed of dry straw, and average foraging areas were 0.91 m2 for C. renggeri and 1.79 m2 for C. rufipes. Inferred intraspecific foraging areas of nearby nests overlapped, especially for C. renggeri. Our findings reinforces the importance of natural history and what it adds to our knowledge on the ecology and behavior of C. renggeri and C. rufipes in Atlantic Forest.
MungeSumstats: A Bioconductor package for the standardisation and quality control of many GWAS summary statistics
Authors: Murphy Alan E , Skene Nathan G 
Published: June 2021

AbstractSummaryGenome-wide association studies (GWAS) summary statistics have popularised and accelerated genetic research. However, a lack of standardisation of the file formats used has proven problematic when running secondary analysis tools or performing meta-analysis studies. To address this issue, we have developed MungeSumstats, a Bioconductor R package for the standardisation and quality control of GWAS summary statistics. MungeSumstats can handle the most common summary statistic formats, including variant call format (VCF) producing a reformatted, standardised, tabular summary statistic file, VCF or R native data object.ContactAlan Murphy:a.murphy@imperial.ac.uk, Nathan Skene:n.skene@imperial.ac.ukAvailability and implementationMungeSumstats is available on Bioconductor (v 3.13) and can also be found on Github at:https://neurogenomics.github.io/MungeSumstatsSupplementary informationThe analysis deriving the most common summary statistic formats is available at:https://al-murphy.github.io/SumstatFormats
FACT-mediated maintenance of chromatin integrity during transcription is essential for mammalian stem cell viability
Authors: Goswami Imon , Sandlesh Poorva , Stablewski Aimee , Toshkov Ilya , Safina Alfiya F , Magnitov Mikhail , Wang Jianmin , Gurova Katerina 
Published: June 2021

AbstractPreservation of nucleosomes during replication has been extensively studied, while the maintenance of nucleosomes during transcription has gotten less attention. The histone chaperone FACT is involved in transcription elongation, although whether it disassembles or assembles nucleosomes during this process is still unclear. We deleted the FACT subunit in adult mice to clarify the function of FACT in mammals. FACT loss was lethal due to the loss of the earliest progenitors in bone marrow and intestine, while mor differentiated cells were not affected. Using cells isolated from several tissues, we showed that FACT loss was lethal only for stem cells but not cells differentiated in vitro. FACT depletion led to increased chromatin accessibility in a transcription-dependent manner, suggesting that nucleosomes are lost during transcription in the absence of FACT. The most prominent response to the loss of nucleosomes was the activation of interferon signaling and the accumulation of immunocytes in sensitive organs. FACT maintained chromatin integrity during transcription in mammalian adult stem cells, suggesting that chromatin transcription in these cells is different from more differentiated cells.
A CRISPR-del-based pipeline for complete gene knockout in human diploid cells
Authors: Komori Takuma , Hata Shoji , Mabuchi Akira , Genova Mariya , Harada Tomoki , Fukuyama Masamitsu , Chinen Takumi , Kitagawa Daiju 
Published: June 2021

AbstractThe advance of CRISPR/Cas9 technology has enabled us easily to generate gene knockout cell lines by introducing insertion/deletion mutations (indels) at the target site via the error-prone non-homologous end joining repair system. Frameshift-promoting indels can disrupt gene functions by generation of a premature stop codon. However, there is growing evidence that targeted genes are not always knocked-out by the indel-based gene disruption. In this study, we established a pipeline of CRISPR-del, which induces a large chromosomal deletion by cutting two different target sites, to perform “complete” gene knockout efficiently in non-transformed human diploid RPE1 cells. By optimizing several procedures, the CRISPR-del pipeline allowed us to generate knockout cell lines harboring bi-allelic large chromosomal deletions in a high-throughput manner. Quantitative analyses show that the frequency of gene deletion with this approach is much higher than that of conventional CRISPR-del methods. The lengths of the deleted genomic regions demonstrated in this study are longer than those of 95% of the human protein-coding genes. Furthermore, the pipeline enables the generation of a model cell line having a bi-allelic cancer-associated chromosomal deletion. Overall, these data lead us to propose that the CRISPR-del pipeline is a high-throughput approach for performing “complete” gene knockout in RPE1 cells.
Inhibiting adenine synthesis attenuates glioblastoma cell stemness and temozolomide resistance
Authors: Singh Simranjit X. , Yang Rui , Roso Kristen , Hansen Landon J. , Du Changzheng , Chen Lee H. , Greer Paula K. , Pirozzi Christopher J. , He Yiping 
Published: June 2021

ABSTRACTGlioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygousMTAPdeletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in adenine salvage, we demonstrate that transient adenine blockade via treatment with L-Alanosine (ALA), an inhibitor ofde novoadenine synthesis, attenuates stemness ofMTAP-deficient GBM cells. This ALA-induced reduction in stemness is accompanied by compromised mitochondrial function, highlighted by diminished spare respiratory capacity. Direct pharmacological inhibition of mitochondrial respiration recapitulates the effect of ALA on GBM cell stemness, suggesting ALA targets stemness partially via affecting mitochondrial function. Finally, in agreement with diminished stemness and compromised mitochondrial function, we show that ALA sensitizes GBM cells to temozolomide (TMZ)in vitroand in an orthotopic GBM model. Collectively, these results identify critical roles of adenine supply in maintaining mitochondrial function and stemness of GBM cells, highlight a critical role of mitochondrial function in sustaining GBM stemness, and implicate adenine synthesis inhibition as a complementary approach for treatingMTAP-deleted GBMs.
Heterogeneous ‘cell types’ can improve performance of deep neural networks
Authors: Doty Briar , Mihalas Stefan , Arkhipov Anton , Piet Alex 
Published: June 2021

AbstractDeep convolutional neural networks (CNNs) are powerful computational tools for a large variety of tasks (Goodfellow, 2016). Their architecture, composed of layers of repeated identical neural units, draws inspiration from visual neuroscience. However, biological circuits contain a myriad of additional details and complexity not translated to CNNs, including diverse neural cell types (Tasic, 2018). Many possible roles for neural cell types have been proposed, including: learning, stabilizing excitation and inhibition, and diverse normalization (Marblestone, 2016; Gouwens, 2019). Here we investigate whether neural cell types, instantiated as diverse activation functions in CNNs, can assist in the feed-forward computational abilities of neural circuits. Our heterogeneous cell type networks mix multiple activation functions within each activation layer. We assess the value of mixed activation functions by comparing image classification performance to that of homogeneous control networks with only one activation function per network. We observe that mixing activation functions can improve the image classification abilities of CNNs. Importantly, we find larger improvements when the activation functions are more diverse, and in more constrained networks. Our results suggest a feed-forward computational role for diverse cell types in biological circuits. Additionally, our results open new avenues for the development of more powerful CNNs.
Adapting macroecology to microbiology: using occupancy modelling to assess functional profiles across metagenomes
Authors: Hilts Angus S. , Hunjan Manjot S. , Hug Laura A. 
Published: June 2021

AbstractMetagenomic sequencing provides information on the metabolic capacities and taxonomic affiliations for members of a microbial community. When assessing metabolic functions in a community, missing genes in pathways can occur in two ways: the genes may legitimately be missing from the community whose DNA was sequenced, or the genes were missed during shotgun sequencing or failed to assemble, and thus the metabolic capacity of interest is wrongly absent from the sequence data. Here, we borrow and adapt occupancy modelling from macroecology to provide mathematical context to metabolic predictions from metagenomes. We review the five assumptions underlying occupancy modelling through the lens of microbial community sequence data. Using the methane cycle, we apply occupancy modelling to examine the presence and absence of methanogenesis and methanotrophy genes from nearly 10,000 metagenomes spanning global environments. We determine that methanogenesis and methanotrophy are positively correlated across environments, and note that the lack of available standardized metadata for most metagenomes is a significant hindrance to large-scale statistical analyses. We present this adaptation of macroecology’s occupancy modelling to metagenomics as a tool for assessing presence/absence of traits in environmental microbiological surveys. We further initiate a call for stronger metadata standards to accompany metagenome deposition, to enable robust statistical approaches in the future.
Mechanisms of DNA repair have evolved to minimise the probability of nonsense mutations
Authors: Powell George , Long Helen S , Versluys Thomas M M , Mallon Ann-Marie , Lindgren Cecilia M , Simon Michelle M 
Published: June 2021

ABSTRACTVariation in sequence mutability has important implications for evolutionary models and predicting disease occurrence, and is driven in part by evolutionary divergence in mechanisms of DNA repair. The aim of this study was twofold: first, to assess the effect of local sequence context on substitution rates in the mouse lineage; second, to investigate the relationship between sequence mutability and selection. We show that the 7-mer context (i.e three bases either side of the base of interest) explains more variation in substitution rates between chromosomes in the mouse lineage than either the 3-mer, 5-mer, or 9-mer contexts. Furthermore, we also show that 7-mer substitutions with the potential to cause nonsense mutations when they occur in translated sequences occur at a lower rate across the genome than 7-mer substitutions with the potential to cause synonymous mutations. We propose that mechanisms of DNA repair have evolved to prioritise substitutions that are more likely to be deleterious to fitness.