bluuebunny/crossref_metadata_2025_split huggingface dataset:
The central nervous system is a potential reservoir and possible origin of drug resistance in HBV
Authors: Xu Lijun , Zhou Minghan , Peng Xiuming , Xu Yufan , Huang Fan , Wang Linyun , Peng Xiaorong , Yang Zongxing , Tao Ran , Lang Guanjing , Cao Qing , Li Minwei , Huang Ying , Zhu Biao , Xu Yan 
Published: April 2023

ABSTRACTThe significance of HBV in cerebrospinal fluid (CSF) is unclear. In the present study,synchronous serum and CSF samples were collected from 13 patients. HBV-DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of reverse transcriptase (RT) region analyses were performed based on PCR and sequencing methods. We found HBV-DNA was detected in the CSF of 3 antiviral-naïve patients and one patient after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 patients, including 2 patients with undetectable serum HBV-DNA. Ten patients exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 patients presented lamivudine/entecavir-associated resistance mutations in only the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV/HBV-coinfected patients than in HBV-monoinfected patients (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P < 0.001; CSF: rtL180M: 7.6% vs. 0, P = 0.026; rtM204I/V 7.6% vs. 1.6%, P = 0.097). Our data suggested CSF is a potential HBV reservoir, and HBV in CSF harbors distinct evolution and mutation models from that in serum. HIV infection increases the possibility of HBV rtL180M and rtM204I/V mutations in both serum and CSF.
Identification of host-interacting domains of surface layer protein B fromLevilactobacillus brevisand the evidence as glycoprotein
Authors: Tan Zheng Lin , Yamamoto Naoyuki 
Published: April 2023

AbstractSurface layer proteins (Slps) can be found on the surface of some lactobacilli which involves in host-interaction and show immunomodulatory activity. Despite the capability of Slps to interact with C-type lectins on antigen presenting cells, present of sugar has not been confirmed except forLentilactobacillus kefiri. In this study, we investigated the presence of sugar moiety in the structure of SlpB fromLevilactobacillus brevis, and its involvement in interaction with DC-SIGN of dendritic cells. 4 fragments of sugar containing fragments were identified in SlpB, and the involvement of sugar in DC-SIGN interaction was confirmed by competitive assay against hexoses. The sequences of these fragments were identified based on the mass obtained from mass spectrometry, and the result has confirmed that these fragments were from carbohydrate binding motifs of SlpB. Analysing the binding affinities of these fragments with surface resonance plasmon analysis suggested that 2 fragments possess higher binding affinity compared to the remaining fragments, and the sum of binding affinities of these fragments was approximate the affinity of intact SlpB.
Phytohormone profiling in an evolutionary framework
Authors: Schmidt Vojtěch , Skokan Roman , Kurtović Katarina , Vosolsobě Stanislav , Filepová Roberta , Haluška Samuel , Dobrev Petre , Motyka Václav , Petrášek Jan 
Published: April 2023

ABSTRACTMultiple phytohormones act as conserved developmental regulators in land plants. Although the closely related streptophyte green algae typically lack full complements of molecular pathways underlying these responses, scattered reports of endogenous phytohormone production in these organisms exist. In this study, we performed a detailed LC/MS-based analysis of several phytohormones, their precursors and metabolites in all lineages of streptophyte algae. We also included chlorophyte algae and early-diverging land plants as outgroups. Free auxin, tRNA-derived cytokinins and certain phenolics including salicylic acid were found ubiquitously. However, land plants differed from green algae by the consistent detection of abscisic acid and the presence of auxin and cytokinin conjugates andtrans-zeatin, supporting the hypotheses that these three phytohormones likely came to regulate development in the ancestral land plant. By contrast, we observed a patchy distribution of jasmonates among streptophytes. We additionaly analyzed the corresponding culture and empty media to account for phytohormone excretion and environmental contamination. Extracellular auxins and cytokinins were frequently detected, while agar constituted a major external source of phenolic compounds. We provide a highly comprehensive evolution-directed screen of phytohormone compound occurrence and thoroughly discuss our data in the context of current plant hormonomics and phylogenomics.GRAPHICAL ABSTRACT
The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system ofdaf-18/PTEN Caenorhabditis elegansmutants
Authors: Giunti Sebastián , Blanco María Gabriela , De Rosa María José , Rayes Diego 
Published: April 2023

AbstractA finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including Autism Spectrum Disorders (ASDs).Mutations in PTEN, the main negative regulator of the PI3K/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using theC. elegansneuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found thatdaf-18/PTENmutations specifically impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The specific defects observed in the GABAergic system indaf-18/PTENmutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function indaf-18/PTENmutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.Highlights*daf-18/PTENdeficiency inC. elegansresults in a specific impairment of inhibitory GABAergic signaling, while the excitatory cholinergic signaling remains unaffected.*The dysfunction of GABAergic neurons in these mutants arises from the inactivity of the transcription factor DAF-16/FOXO during their development, resulting in conspicuous morphological and functional alterations.*A diet enriched with the ketone body β-hydroxybutyrate, which induces DAF-16/FOXO activity, mitigates the functional and morphological defects in the development of GABAergic neurons*β-hydroxybutyrate supplementation during the early stages of development is both necessary and sufficient to achieve these rescuing effects on GABAergic signaling indaf-18/PTENmutants.Graphical Abstract
Topographic barriers drive the pronounced genetic subdivision of a range-limited fossorial rodent
Authors: Reuber Victoria M. , Westbury Michael V. , Rey-Iglesia Alba , Asefa Addisu , Farwig Nina , Miehe Georg , Opgenoorth Lars , Sumbera Radim , Wraase Luise , Wube Tilaye , Lorenzen Eline D. , Schabo Dana G. 
Published: April 2023

AbstractDue to their limited dispersal ability, fossorial species with predominantly belowground activity usually show increased levels of population subdivision across relatively small spatial scales. This may be exacerbated in harsh mountain ecosystems, where landscape geomorphology limits species’ dispersal ability and leads to small effective population sizes, making species susceptible to environmental change. The giant root-rat (Tachyoryctes macrocephalus) is a highly fossorial rodent confined to the afro-alpine ecosystem of the Bale Mountains in Ethiopia. Using mitochondrial and low-coverage nuclear genomes, we investigated 77 giant root-rat individuals sampled from nine localities across its whole ∼1,000 km2range. Our data revealed a distinct division into a northern and southern subpopulation, with no signs of gene flow, and higher nuclear genetic diversity in the south. Landscape genetic analyses of the mitochondrial genomes indicated that population subdivision was driven by steep slopes and elevation differences of up to 500 m across escarpments separating the north and south, potentially reinforced by glaciation of the south during the Late Pleistocene (∼42,000 to 16,000 years ago). Despite the pronounced subdivision observed at the range-wide scale, weak geographic structuring of sampling localities within subpopulations indicated gene flow across distances of at least 16 km, suggesting aboveground dispersal and high mobility for relatively long distances. Our study highlights how topographic barriers can lead to the genetic subdivision of fossorial species, despite their potential to maintain gene flow at the local scale. These factors can reduce genetic variability, which should be considered when developing conservation strategies.
Benchmarking imputation methods for discrete biological data
Authors: Gendre Matthieu , Hauffe Torsten , Pimiento Catalina , Silvestro Daniele 
Published: April 2023

AbstractTrait datasets are at the basis of a large share of ecology and evolutionary research, being used to infer ancestral morphologies, to quantify species extinction risks, or to evaluate the functional diversity of biological communities. These datasets, however, are often plagued by missing data, for instance due to incomplete sampling limited data and resource availabilities. Several imputation methods exist to predict missing values and have been successfully evaluated and used to fill the gaps in datasets of quantitative traits. Here we explore the performance of different imputation methods on discrete biological traits i.e. qualitative or categorical traits such as diet or habitat. We develop a bioinformatics pipeline to impute trait data combining phylogenetic, machine learning, and deep learning methods while integrating a simulation framework to evaluate their performance on synthetic datasets. Using this pipeline we run a wide range of simulations under different missing rates, mechanisms, and biases and different evolutionary models. Our results indicate that a new ensemble approach, where we combined the imputation results of a selection of imputation methods provides the most robust and accurate prediction of missing discrete traits. We apply our pipeline to an incomplete trait dataset of 1015 elasmobranch species (including sharks and rays) and found a high imputation accuracy of the predictions based on an expert-based assessment of the missing traits. Our bioinformatic pipeline, implemented in an open-source R package, facilitates the application and comparison of multiple imputation methods to make robust predictions of missing trait values in biological datasets.
bettercallsal: better calling ofSalmonellaserotypes from enrichment cultures using shotgun metagenomic profiling and its application in an outbreak setting
Authors: Konganti Kranti , Reed Elizabeth , Mammel Mark , Kayikcioglu Tunc , Binet Rachel , Jarvis Karen , Ferreira Christina M. , Bell Rebecca L. , Zheng Jie , Windsor Amanda M. , Ottesen Andrea , Grim Christopher , Ramachandran Padmini 
Published: April 2023

AbstractPrecise and rapid identification ofSalmonellaserotypes from suspect food matrices is critical for successful source attribution of illness outbreaks (Scallan et al., 2011). Currently, close to 3% of U.S. foodborneSalmonellaoutbreaks have been attributed to multiple Salmonellaserotypes (2.85%, 2000 - 2020) (CDC, 2022). Recent foodborne outbreaks that have been attributed to multipleSalmonellaserotypes force us to question whether these are rare events or if previous methods simply did not have the throughput to provide an accurate picture of the complex ecology that is connected to outbreak etiologies. (Hassan et al., 2019; FDA, 2021; Whitney et al., 2021).Anin-silicobenchmark dataset, comprising 29 uniqueSalmonella, 46 non-Salmonellabacterial and 10 viral genomes, was generated with varying read depths. For outbreak samples, analysis was performed on previously sequenced pre-enrichments and selective enrichments of papayas and peaches (fruits and leaves) that led to the identification of multiple serovars. Data analyses was performed using a custom-builtk-mertool, SeqSero2, Kallisto and bettercallsal.Thein-silicodataset analyzed with bettercallsal had accuracy, recall and specificity of 95%, 96% and 98 % respectively. In the papaya outbreak samples, bettercallsal identified multiple serovar presence in concordance with Bioplex assay results and the genome hits assigned to the samples areSalmonellaisolates from the papaya outbreak as evident by NCBI SNP cluster information. In peach outbreak samples, bettercallsal identified both the serovars (Alachua and Gaminara) in concordance withk-mer analysis and the Luminex xMap assay. bettercallsal outperformedk-mer, Kallisto and Seqsero2 in identifying multiple serovars from enrichment cultures using shotgun metagenomics sequencing.MostSalmonellasubtyping work has relied upon WGS methods which focuses on the high-resolution analysis of single genomes, or multiple single genomes picked from colonies on agar. Here we introduce laboratory and bioinformatics innovations for a metagenomic outbreak response workflow that accurately identifies multipleSalmonellaserovars at the same time in a much higher throughput approach. bettercallsal is one of the first analysis tools that can potentially identify multipleSalmonellaspp. serotypes from a metagenomic or quasi-metagenomic datasets with accuracy and can provide early insights into the etiology of the sample.
Single-cell transcriptome analysis reveals the cellular atlas of human intracranial aneurysm and highlights inflammation features associated with aneurysm rupture
Authors: Ji Hang , Li Yue , Sun Haogeng , Chen Ruiqi , Zhou Ran , Xiao Anqi , Yang Yongbo , Wang Rong , You Chao , Liu Yi 
Published: April 2023

AbstractIntracranial aneurysm (IA) is pouch-like pathological dilations of cerebral arteries, which often affects middle-aged people and culminates in life-threatening hemorrhagic stroke. A deeper knowledge of the cellular and gene expression perturbations in human IA tissue deepens our understanding of disease mechanisms and facilitates developing pharmacological targets for unruptured IA. In this study, 21,332 qualified cells were obtained from cell-sparse ruptured and unruptured human IA tissues and a detailed cellular profile was determined, including conventional endothelial cells, smooth muscle cells (SMC), fibroblasts and the newly identified pericytes. Notably, striking proportion of immune cells were identified in IA tissue, with the number of monocyte/macrophages and neutrophils being remarkably higher in ruptured IA. By leveraging external datasets and machine learning algorithms, a subset of macrophages characterized by high expression of CCL3 and CXCL3, and transcriptional activation of NF-κB and HIVEP2 was identified as the cell most associated with IA rupture. Further, the interactome of CCL3/CXCL3 macrophages disclosed their role in regulating vascular cell survival and orchestrating inflammation. In summary, this study illustrated the profile and interactions of vascular and immune cells in human IA tissue and the opportunities for targeting local chronic inflammation.
Interferon ε restricts Zika virus infection in the female reproductive tract
Authors: Xu Chuan , Wang Annie , Ebraham Laith , Sullivan Liam , Tasker Carley , Pizutelli Vanessa , Couret Jennifer , Hernandez Cyril , Deb Pratik Q. , Fritzky Luke , Subbian Selvakumar , Gao Nan , Lo Yungtai , Salvatore Mirella , Rivera Amariliz , Lemenze Alexander , Fitzgerald-Bocarsly Patricia , Tyagi Sanjay , Lu Wuyuan , Beaulieu Aimee , Chang Theresa L. 
Published: April 2023

AbstractInterferon ε (IFNε) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNε contributes to protection against ZIKV infectionin vivois unknown. Here, we show that IFNε plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNε was expressed not only by epithelial cells in the FRT, but also by certain immune and other cells at baseline or after exposure to viruses or specific TLR agonists. IFNε-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal, but not subcutaneous ZIKV infection. IFNε-deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNε protectedIfnε-/-mice and highly susceptibleIfnar1-/-mice against vaginal ZIKV infection, indicating that IFNε was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFNε in mediating protection against transmission of ZIKV in the context of sexual contact.SignificanceInterferon ε (IFNε), a unique Type I IFN that is highly expressed in the epithelium of the female reproductive tract (FRT), is thought to protect the host against sexually transmitted infections (STIs) but the mechanism of action is not defined. Zika virus (ZIKV), a causative agent for preterm birth and other severe diseases in pregnant women, can be spread through vaginal transmission. Here, we show that mice lacking theIfnεgene have abnormal epithelial development and tissue architecture in the cervicovaginal tract. The role of IFNε in protecting host against ZIKV is FRT-specific and is independent of IFNAR1 signaling. Our findings suggest potential preventive strategies based on harnessing mucosal immunity against STIs.
A clinical study to evaluate the safe and effective use of Stethoglove, a single use stethoscope cover to reduce pathogen transmission during auscultation
Authors: Nazari-Shafti Timo Z. , Meyborg Heike , Iske Jasper , Schloss Maximilian , Seeber Fabian , Friedrich Aljona , Exarchos Vasileios , Richter Anja , Falk Volkmar , Emmert Maximilian Y 
Published: April 2023

ABSTRACTObjectivesStethoscopes carry a significant risk for pathogen transmission. Here, the safe use and performance of Stethoglove®, a non-sterile, single-use cover for stethoscopes, that is impermeable for pathogens, was investigated by different healthcare professionals (HCPs) in the postoperative care setting of an intensive care unit (ICU).MethodsFifty-four patients underwent routine auscultations with the use of Stethoglove®. The participating HCPs (n=34) rated each auscultation with Stethoglove®on a 5-point Likert scale. The mean ratings of acoustic quality and Stethoglove®handling were defined as primary and secondary performance endpoint.Results534 auscultations with Stethoglove®were performed (average 15.7/user) on the lungs (36.1%), the abdomen (33.2%), the heart (28.8%) or other body-sites (1.9%). No adverse device-effects occurred. The acoustic quality was rated at 4.2±0.7 (mean) with a total of 86.1% of all auscultations being rated at least as 4/5, and with no rating as below 2. The Stethoglove®handling was rated at 3.7±0.8 (mean) with a total of 96.4% of all auscultations being rated at least 3/5.ConclusionsUsing a real-world setting, this study demonstrates that Stethoglove®can be safely and effectively used as cover for stethoscopes during auscultation. Stethoglove®may therefore represent a useful and easy-to-implement tool for preventing stethoscope-mediated infections.
Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics
Authors: Wallace Rachel P. , Refvik Kirsten C. , Antane Jennifer T. , Brünggel Kym , Tremain Andrew C. , Raczy Michal R. , Alpar Aaron T. , Nguyen Mindy , Solanki Ani , Slezak Anna J. , Watkins Elyse A. , Lauterbach Abigail L. , Cao Shijie , Wilson D. Scott , Hubbell Jeffrey A. 
Published: April 2023

SummaryImmunogenic biologics trigger an anti-drug antibody (ADA) response in patients, which reduces efficacy and increases adverse reactions. Our laboratory has previously shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer (p(Man)). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We found that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by Tregs. We identify increased TCR signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.
Coding of time with non-linear mixed selectivity in Prefrontal Cortex ensembles
Authors: Mikkelsen Catherine A. , Charczynski Stephen J. , Brincat Scott K. , Warden Melissa R. , Miller Earl K. , Howard Marc W. 
Published: April 2023

AbstractPrevious work has identified stimulus specific time cells as a potential mechanism for working memory maintenance. It has been proposed that populations of stimulus specific sequences of cells could support memory for many items in a list over long periods of time. This would require information about one stimulus to persist after the presentation of subsequent stimuli. However, it is not known if sequences triggered by one stimulus persist past the presentation of additional stimuli. It is possible that each new stimulus terminates preceding sequences, making memory for multiple stimuli impossible. To investigate this question, we utilized a data set originally published by (Warden & Miller, 2010), studying the firing of monkey prefrontal neurons during short lists of stimuli. We were able to decode “what happened when” throughout the list, using linear discriminant analysis. Additionally, we were able to decode the first stimulus after the presentation of the second stimulus. Furthermore, we found that stimulus modulated sequences of cells, with discrete temporal fields, continue after the second item was presented. Much of the information about the previous item was carried by neurons that responded to conjunctions of stimuli and the timing of late-firing cells was synchronized to the firing of the second stimulus rather than the first. These properties falsify a simple linear model of sequential time cells. These results suggest that non-linear mixed selectivity extends to continuous variables such as time, but that in this experiment at least, only the timing of the most recent stimulus was explicitly maintained in ongoing firing.