bluuebunny/crossref_metadata_2025_split huggingface dataset:
An accessible, efficient and global approach for the large-scale sequencing of bacterial genomes
Authors: Perez-Sepulveda Blanca M. , Heavens Darren , Pulford Caisey V. , Predeus Alexander V. , Low Ross , Webster Hermione , Schudoma Christian , Rowe Will , Lipscombe James , Watkins Chris , Kumwenda Benjamin , Shearer Neil , Costigan Karl , Baker Kate S. , Feasey Nicholas A. , Hinton Jay C. D. , Hall Neil ,   The 10KSG consortium
Published: July 2020

AbstractWe have developed an efficient and inexpensive pipeline for streamlining large-scale collection and genome sequencing of bacterial isolates. Evaluation of this method involved a worldwide research collaboration focused on the model organismSalmonella enterica, the 10KSG consortium. By optimising a logistics pipeline that collected isolates as thermolysates, permitting shipment in ambient conditions, the project assembled a diverse collection of 10,419 clinical and environmental isolates from low- and middle-income countries in less than one year. The bacteria were obtained from 51 countries/territories dating from 1949 to 2017, with a focus on Africa and Latin-America. All isolates were collected in barcoded tubes and genome sequenced using an optimised DNA extraction method and the LITE pipeline for library construction. After Illumina sequencing, the total reagent cost was less than USD$10 per genome. Our method can be applied to genome-sequence other large bacterial collections at a relatively low cost, within a limited timeframe, to support global collaborations.
The soluble glutathione transferase superfamily: Role of Mu class in Triclabendazole sulphoxide challenge inFasciola hepatica
Authors: Stuart Rebekah B. , Zwaanswijk Suzanne , MacKintosh Neil D. , Witikornkul Boontarikaan , Prescott Mark , Brophy Peter M. , Morphew Russell M. 
Published: July 2020

AbstractFasciola hepatica(liver fluke), a significant threat to food security, causes global economic loss for the livestock production industry and is re-emerging as a food borne disease of humans. In the absence of vaccines the commonly used method of treatment control is by anthelmintics; with only Triclabendazole (TCBZ) currently effective against all stages ofF. hepaticain livestock and humans. There is widespread resistance to TCBZ and detoxification by flukes might contribute to the mechanism. However, there is limited Phase I capacity in adult parasitic helminths and the major Phase II detoxification system in adults is the soluble Glutathione transferases (GST) superfamily. Previous global proteomic studies have shown that the levels of Mu class GST from pooledF. hepaticaparasites respond under TCBZ-Sulphoxide (TCBZ-SO), the likely active metabolite, challenge duringin vitroculture ex-host. We have extended this finding by using a sub-proteomic lead approach to measure the change in the total soluble GST profile (GST-ome) of individual TCBZ susceptibleF. hepaticaon TCBZ-SO-exposurein vitroculture. TCBZ-SO exposure demonstrated a FhGST-Mu29 and FhGST-Mu26 response following affinity purification using both GSH and S-hexyl GSH affinity resins. Furthermore, a low affinity Mu class GST (FhGST-Mu5) has been identified and recombinantly expressed and represents a novel low affinity mu class GST. Low affinity GST isoforms within the GST-ome was not limited to FhGST-Mu5 with second likely low affinity sigma class GST (FhGST-S2) uncovered through genome analysis. This study represents the most completeFasciolaGST-ome generated to date and has supported the sub proteomic analysis on individual adult flukes.
From people toPanthera: Natural SARS-CoV-2 infection in tigers and lions at the Bronx Zoo
Authors: McAloose Denise , Laverack Melissa , Wang Leyi , Killian Mary Lea , Caserta Leonardo C. , Yuan Fangfeng , Mitchell Patrick K. , Queen Krista , Mauldin Matthew R. , Cronk Brittany D. , Bartlett Susan L. , Sykes John M. , Zec Stephanie , Stokol Tracy , Ingerman Karen , Delaney Martha A. , Fredrickson Richard , Ivančić Marina , Jenkins-Moore Melinda , Mozingo Katie , Franzen Kerrie , Bergeson Nichole Hines , Goodman Laura , Wang Haibin , Fang Ying , Olmstead Colleen , McCann Colleen , Thomas Patrick , Goodrich Erin , Elvinger François , Smith David C. , Tong Suxiang , Slavinski Sally , Calle Paul P. , Terio Karen , Torchetti Mia Kim , Diel Diego G. 
Published: July 2020

AbstractWe describe the first cases of natural SARS-CoV-2 infection detected in animals in the United States. In March 2020, four tigers and three lions at the Bronx Zoo developed mild respiratory signs. SARS-CoV-2 RNA was detected by rRT-PCR in respiratory secretions and/or feces from all seven affected animals; viral RNA and/or antibodies were detected in their keepers. SARS-CoV-2 was isolated from respiratory secretions or feces from three affected animals;in situhybridization co-localized viral RNA with cellular damage. Whole genome sequence and haplotype network analyses showed tigers and lions were infected with two different SARS-CoV-2 strains, suggesting independent viral introductions. The source of SARS-CoV-2 infection in the lions is unknown. Epidemiological data and genetic similarities between keeper and tiger viruses indicate human to animal transmission.
Host responses in anex-vivohuman skin model challenged withMalassezia sympodialis
Authors: Corzo Leon Dora E. , MacCallum Donna M. , Munro Carol A. 
Published: July 2020

ABSTRACTMalasseziaspecies are a major part of the normal mycobiota and colonise mainly sebum-rich skin regions of the body. This group of fungi cause a variety of infections such as pityriasis versicolour, folliculitis and fungaemia. In particular,Malassezia sympodialisand its allergens have been associated with non-infective inflammatory diseases such as seborrheic dermatitis and atopic eczema. The aim of this study was to investigate the host response toM. sympodialison oily skin (supplemented with oleic acid) and non-oily skin using anex-vivohuman skin model. Host-pathogen interactions were analysed by SEM, histology, gene expression, immunoassays and dual species proteomics. The skin response toM. sympodialiswas characterised by increased expression of the genes encoding β-defensin 3 and RNase7, and by high levels of S100 proteins in tissue. Supplementation of oleic acid onto skin was associated with direct contact of yeasts with keratinocytes and epidermal damage. In oily conditions, skin response toM. sympodialisshowed no gene expression of AMPs, but increased expression ofIL18. In supernatants from inoculated skin plus oleic acid, TNFα levels were decreased and IL-18 levels were significantly increased.
Genome-wide association study and polygenic risk score analysis for hearing measures in children
Authors: Schmitz Judith , Abbondanza Filippo , Paracchini Silvia 
Published: July 2020

AbstractAn efficient auditory system contributes to cognitive and psychosocial development. A right ear advantage in hearing thresholds (HT) has been described in adults and atypical patterns of left/right hearing threshold asymmetry (HTA) have been described for psychiatric and neurodevelopmental conditions. Previous genome-wide association studies (GWAS) on HT have mainly been conducted in elderly participants whose hearing is more likely to be affected by external environmental factors. We analyzed HT and HTA in a children population cohort (ALSPAC,n= 6,743). Better hearing was associated with better cognitive performance and higher socioeconomic status (SES). At the group level, HTA suggested a left ear advantage (mean = -0.28 dB) that was mainly driven by females. SNP heritability for HT and HTA was 0.17 and 0.01, respectively (n= 5,344). Genetic correlation analysis confirmed associations between HT, reading ability, listening comprehension, and GCSE scores. GWAS for HT did not yield significant hits but polygenic risk score (PRS) analysis showed significant associations of higher educational attainment (EA, ß = -1564.72, p = .008) and risk for schizophrenia (ß = -241.14, p = .004) with lower HT, i.e. better hearing. In summary, we report new data supporting associations between hearing measures and cognitive abilities at the behavioral level. Genetic analysis suggests shared biological pathways between cognitive and sensory systems and provides evidence for a positive outcome of genetic risk for schizophrenia.
Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization
Authors: Matsumura Kazuki , Shimomura Takushi , Kubo Yoshihiro , Oka Takayuki , Kobayashi Naohiro , Imai Shunsuke , Yanase Naomi , Akimoto Madoka , Fukuda Masahiro , Yokogawa Mariko , Ikeda Kazuyoshi , Kurita Jun-ichi , Nishimura Yoshifumi , Shimada Ichio , Osawa Masanori 
Published: July 2020

AbstractHumanether-à-go-go-related gene potassium channel 1 (hERG) is a voltage-gated potassium channel, the voltage-sensing domain (VSD) of which is targeted by a gating-modifier toxin, APETx1. Although it is known that APETx1 inhibits hERG by stabilizing the resting state, it remains unclear where and how APETx1 interacts with the VSD in the resting state. Here, we prepared a recombinant APETx1, which is structurally and functionally equivalent to the natural product. Electrophysiological analyses using wild type and mutants of APETx1 and hERG revealed that their hydrophobic residues, in addition to a previously reported acidic hERG residue, play key roles in the inhibition of hERG by APETx1. Docking models of the APETx1-VSD complex that satisfy the results of mutational analysis suggest a molecular recognition mode between APETx1 and the resting state of hERG; this would provide a structural basis for designing ligands that control hERG function by binding to the VSD.
Distinct networks coupled with parietal cortex for spatial representations inside and outside the visual field
Authors: Zhang Bo , Wang Fan , Zhang Qi , Yuji Naya 
Published: July 2020

AbstractOur mental representation of egocentric space is influenced by the disproportionate sensory perception of the body. Previous studies have focused on the neural architecture for egocentric representations within the visual field. However, the space representation underlying the body is still unclear. To address this problem, we applied both fMRI and MEG to a spatial-memory paradigm by using a virtual environment in which human participants remembered a target location left, right, or back relative to their own body. Both experiments showed larger involvement of the frontoparietal network in representing a retrieved target on the left/right side than on the back. Conversely, the medial temporal lobe (MTL)-parietal network was more involved in retrieving a target behind the participants. The MEG data showed preferential connectivity in the alpha-band frequency in both networks. These findings suggest that the parietal cortex may represent the entire space around the self-body by coordinating two distinct brain networks.
Identifying transcription patterns of histology and radiomics features in NSCLC with neural networks
Authors: Smedley Nova F. , Aberle Denise R. , Hsu William 
Published: July 2020

AbstractPurposeTo investigate the use of deep neural networks to learn associations between gene expression and radiomics or histology in non-small cell lung cancer (NSCLC).Materials and MethodsDeep feedforward neural networks were used for radio-genomic mapping, where 21,766 gene expressions were inputs to individually predict histology and 101 CT radiomic features. Models were compared against logistic regression, support vector machines, random forests, and gradient boosted trees on 262 training and 89 testing patients. Neural networks were interpreted using gene masking to derive the learned associations between subsets of gene expressions to a radiomic feature or histology type.ResultsNeural networks outperformed other classifiers except in five radiomic features, where training differences were <0.026 AUC. In testing, neural networks classified histology with AUCs of 0.86 (adenocarcinoma), 0.91 (squamous), and 0.71 (other); and 14 radiomics features with >= 0.70 AUC. Gene masking of the models showed new and previously reported histology-gene or radiogenomic associations. For example, hypoxia genes could predict histology with >0.90 test AUC and published gene signatures for histology prediction were also predictive in our models (>0.80 test AUC). Gene sets related to the immune or cardiac systems and cell development processes were predictive (>0.70 test AUC) of several different radiomic features while AKT signaling, TNF, and Rho gene sets were each predictive of tumor textures.ConclusionWe demonstrate the ability of neural networks to map gene expressions to radiomic features and histology in NSCLC and interpret the models to identify predictive genes associated with each feature or type.Author SummaryNon-small-cell lung cancer (NSCLC) patients can have different presentations as seen in the CT scans, tumor gene expressions, or histology types. To improve the understanding of these complementary data types, this study attempts to map tumor gene expressions associated with a patient’s CT radiomic features or a histology type. We explore a deep neural network approach to learn gene-radiomic associations (i.e., the subsets of co-expressed genes that are predictive of a value of an individual radiomic feature) and gene-histology associations in two separate public cohorts. Our modeling approach is capable of learning relevant information by showing the model can predict histology and that the learned relationships are consistent with prior works. The study provides evidence for coherent patterns between gene expressions and radiomic features and suggests such integrated associations could improve patient stratification.
Sensory processing and participation in childhood occupation in Autism and Typically developing children - A cross sectional case control
Authors: Loh Siew Yim , Ee Su Im , Marret Mary J. , Chinna Karuthan 
Published: July 2020

AbstractBackgroundSensory processing difficulties and participation in childhood occupation in children impact their development, but the association among Malaysian children is unknown. The aim of this study is to provide empirical evidences on sensory processing and participation in childhood occupation, in children with autism and compare them with typical children without autism /’typical’.MethodTwo groups of participants (parents of children with autism and parents of ‘normal’ children were recruited from 5 hospitals, and from tuition/care centre/school respectively. Children with autism, age 6 to 10 years were matched (age/gender) with ‘typical’ children. The Participation of childhood occupation (PICO) and Sensory Processing (SSP) measures were used. Data were analysed descriptively for patterns, and Chi-square cross tabs used to compare sensory processing and participation (categorical variables) between the two groups.Results186 parents (93 children with autism and 93 typically developing children) participated. In the autism group, 77.4 percent (n=72) were males, or 4:1 male to female ratio. Children with autism compared with typical group experienced- a) higher sensory processing difficulties and b) less participation in childhood occupation (except basic activities like eating and sleep). Sensory processing difficulties in the autism children is lower compared to developed countries, but, the prevalence of sensory processing difficulties in the ‘typical’ children (21.5 percent) was higher than data from USA and Israel (9-15%). There were significant differences in sensory processing difficulties between the two group (p<0.05), except for movement sensitivity (p=0.28). Auditory filtering section were most affected in children with autism.ConclusionDifferences were found in the sensory processing difficulties (especially auditory filtering) and lower participation in autism group compared to ‘normal’ group. A higher percentage of sensory processing difficulties was also found in the ‘normal/ typically developing children’, which may be attributed to cultural or geographical factors (living in high rise flats with less playing space). More studies are needed comparing rural and urban children.
Pain burden, sensory profile and inflammatory cytokines of dogs with naturally-occurring neuropathic pain treated with gabapentin alone or with meloxicam
Authors: Ruel Hélène L.M. , Watanabe Ryota , Evangelista Marina C. , Beauchamp Guy , Auger Jean-Philippe , Segura Mariela , Steagall Paulo V. 
Published: July 2020

ABSTRACTCanine neuropathic pain (NeuP) has been poorly investigated. This study aimed to evaluate the pain burden, sensory profile and inflammatory cytokines in dogs with naturally-occurring NeuP. Twenty-nine client-owned dogs with NeuP were included in a prospective, partially masked, randomized crossover clinical trial, and treated with gabapentin/placebo/gabapentin-meloxicam or gabapentin-meloxicam/placebo/gabapentin (each treatment block of 7 days; total 21 days). Pain scores, mechanical (MNT) and electrical (ENT) nociceptive thresholds and descending noxious inhibitory controls (DNIC) were assessed at baseline, days 7, 14, and 21. DNIC was evaluated using ΔMNT (after-before conditioning stimulus). Positive or negative ΔMNT corresponded to inhibitory or facilitatory pain profiles, respectively. Data from baseline were compared to those of sixteen healthy controls. ΔMNT, but not MNT and ENT, was significantly larger in controls (2.3 ± 0.9 N) than in NeuP (−0.2 ± 0.7 N). The percentage of dogs with facilitatory sensory profile was similar at baseline and after placebo (61.5-63%), and between controls and after gabapentin (33.3-34.6%). Pain scores were lower than baseline after gabapentin or gabapentin-meloxicam. Cytokine levels were not different between groups or treatments. Dogs with NeuP have deficient inhibitory pain mechanisms. Pain burden was reduced after gabapentin and gabapentin-meloxicam depending on the pain scoring instrument used.
Protective mutation A673T as a potential gene therapy for most forms of APP Familial Alzheimer’s Disease
Authors: Guyon Antoine , Rousseau Joël , Lamothe Gabriel , Tremblay Jacques P. 
Published: July 2020

AbstractThe accumulation of plaque in the brain leads to the onset and development of Alzheimer’s disease. The Amyloid precursor protein (APP) is usually cut by α-secretase, however an abnormal cleavage profile by β-secretase (BACE1) leads to the accumulation of Aβ peptides, which forms these plaques. Numerous APP gene mutations favor plaque accumulation, causing Familial Alzheimer Disease (FAD). However, a variant of the APP gene (A673T) in Icelanders reduces BACE1 cleavage by 40 %. A library of plasmids containing APP genes with 29 FAD mutations with or without the additional A673T mutation was generated and transfected in neuroblastomas to assess the effect of this mutation on Aβ peptide production. In most cases the production of Aβ peptides was decreased by the co-dominant A673T mutation. The reduction of Aβ peptide concentrations for the London mutation (V717I) even reached the same level as A673T carriers. These results suggest that the insertion of A673T in the APP gene of genetically susceptible FAD patients may prevent the onset of, slow down, or stop the progression of the disease.
Long-reads assembly of theBrassica napusreference genome, Darmor-bzh
Authors: Rousseau-Gueutin Mathieu , Belser Caroline , Silva Corinne Da , Richard Gautier , Istace Benjamin , Cruaud Corinne , Falentin Cyril , Boideau Franz , Boutte Julien , Delourme Regine , Deniot Gwenaëlle , Engelen Stefan , de Carvalho Julie Ferreira , Lemainque Arnaud , Maillet Loeiz , Morice Jérôme , Wincker Patrick , Denoeud France , Chèvre Anne-Marie , Aury Jean-Marc 
Published: July 2020

AbstractBackgroundThe combination of long-reads and long-range information to produce genome assemblies is now accepted as a common standard. This strategy not only allow to access the gene catalogue of a given species but also reveals the architecture and organisation of chromosomes, including complex regions like telomeres and centromeres. TheBrassicagenus is not exempt and many assemblies based on long reads are now available. The reference genome forBrassica napus, Darmor-bzh, which was published in 2014, has been produced using short-reads and its contiguity was extremely low if compared to current assemblies of theBrassicagenus.FindingsHere, we report the new long-reads assembly of Darmor-bzh genome (Brassica napus) generated by combining long-reads sequencing data, optical and genetic maps. Using the PromethION device and six flowcells, we generated about 16M long-reads representing 93X coverage and more importantly 6X with reads longer than 100Kb. This ultralong-reads dataset allows us to generate one of the most contiguous and complete assembly of aBrassicagenome to date (contigs N50 > 10Mb). In addition, we exploited all the advantages of the nanopore technology to detect modified bases and sequence transcriptomic data using direct RNA to annotate the genome and focus on resistance genes.ConclusionUsing these cutting edge technologies, and in particular by relying on all the advantages of the nanopore technology, we provide the most contiguousBrassica napusassembly, a resource that will be valuable for theBrassicacommunity for crop improvement and will facilitate the rapid selection of agronomically important traits.
The roles of history, chance, and natural selection in the evolution of antibiotic resistance
Authors: Santos-Lopez Alfonso , Marshall Christopher W. , Welp Allison L. , Turner Caroline , Rasero Javier , Cooper Vaughn S. 
Published: July 2020

AbstractHistory, chance, and selection are the fundamental factors that drive and constrain evolution. We designed evolution experiments to disentangle and quantify effects of these forces on the evolution of antibiotic resistance. History was established by prior antibiotic selection of the pathogenAcinetobacter baumanniiin both structured and unstructured environments, selection occurred in increasing concentrations of new antibiotics, and chance differences arose as random mutations among replicate populations. The effects of history were reduced by increasingly strong selection in new drugs, but not erased, at times producing important contingencies. Selection in structured environments constrained resistance to new drugs and led to frequent loss of resistance to the initial drug. This research demonstrates that despite strong selective pressures of antibiotics leading to genetic parallelism, history can etch potential vulnerabilities to orthogonal drugs.