bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene inversion triggered origination of brackish archaeal heterotrophs in the aftermath of the Cryogenian Snowball Earth
Authors: Fan Lu , Xu Bu , Chen Songze , Liu Yang , Li Fuyan , Xie Wei , Prabhu Apoorva , Zou Dayu , Wan Ru , Li Hongliang , Liu Haodong , Liu Yuhang , Kao Shuh-Ji , Chen Jianfang , Zhu Yuanqing , Rinke Christian , Li Meng , Zhu Maoyan , Zhang Chuanlun 
Published: September 2022

AbstractLand-ocean interactions greatly impacted the evolution of coastal life on Earth. However, the geological forces and genetic mechanisms that shaped evolutionary adaptations and allowed microorganisms to inhabit coastal brackish waters remain largely unexplored. Here, we infer the evolutionary trajectory of the ubiquitous heterotrophic archaeaPoseidoniales(Marine Group II archaea) across global aquatic habitats. Our results show that their brackish subgroups have evolved through the rearrangement of the magnesium transport genecorAthat conferred osmotic-stress tolerance dated to over 600 million years ago. The coastal family ofPoseidonialesshowed a rapid increase in the evolutionary rate during and in the aftermath of the Cryogenian Snowball Earth (~700 million years ago), possibly in response to the enhanced phosphorus supply and the rise of algae. Our study highlights the close interplay between genetic changes and ecosystem transformations that boosted microbial diversification in the Neoproterozoic continental margins.
Genetic correlations between gut microbiota genera and Alzheimer’s Disease
Authors: Cammann Davis , Lu Yimei , Cummings Melika J. , Zhang Mark L. , Cue Joan Manual , Do Jenifer , Ebersole Jeffrey , Chen Xiangning , Oh Edwin C. , Cummings Jeffrey L. , Chen Jingchun 
Published: September 2022

1.AbstractBackgroundDysbiosis of the human gut microbiota has been implicated in the development of Alzheimer’s disease (AD). However, the genetic correlation between gut microbiota and AD is not well addressed.MethodsUsing the largest genome-wide association study (GWAS) of gut microbiota genera from the MiBioGen consortium, we conducted the “best-fit” model from PRSice-2 to determine the genetic correlation between 119 genera and AD in a discovery sample (case/control: 1,278/1,293); we then replicated our findings in an independent sample (case/control: 799/778) and further performed meta-analyses to confirm the correlation. Finally, we conducted a linear regression to assess the correlation between the PRSs for the significant genera and theAPOEgenotype.ResultsIn the discovery sample, 20 gut microbiota genera were initially identified genetically associated with AD. Three genera (Eubacterium fissicatenaas a protective factor,CollinsellaandVeillonellaas a risk factor) were validated in the replication sample. Meta-analysis confirmed nine genera to have a significant correlation with AD, three of which were significantly associated with theAPOErs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genusCollinsella, identified as a risk factor for AD, was positively correlated with theAPOErs429358 risk allele in both samples.ConclusionHost genetic factors influencing the abundance of nine genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction withAPOE. Larger datasets and functional studies are required to understand their causal relationships.
Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study
Authors: Drain Paul K. , Dalmat Ronit R. , Hao Linhui , Bemer Meagan J. , Budiawan Elvira , Morton Jennifer F. , Ireton Renee C. , Hsiang Tien-Ying , Marfatia Zarna , Prabhu Roshni , Woosley Claire , Gichamo Adanech , Rechkina Elena , Hamilton Daphne , Montaño Michalina , Cantera Jason L. , Ball Alexey S. , Golez Inah , Smith Elise , Greninger Alexander L. , McElrath M. Juliana , Thompson Matthew , Grant Benjamin D. , Meisner Allison , Gottlieb Geoffrey S. , Gale Michael J. 
Published: September 2022

AbstractBackgroundGuidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing.MethodsWe enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by a positive viral culture.ResultsAmong 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, viral culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, viral cultures and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with viral culture positivity (relative risk=7.61, 95% CI: 3.01-19.2), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, presence of N antigen (adjusted relative risk=7.66, 95% CI: 3.96-14.82), remained strongly associated with viral culture positivity, regardless of COVID-19 symptoms.ConclusionsMost adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset, and N antigen testing is a strong predictor of viral infectiousness. Within two weeks from symptom onset, N antigen testing, rather than absence of symptoms or viral RNA, should be used to safely discontinue isolation.FundingBill and Melinda Gates Foundation
The Nematode Antimicrobial Peptidome: a novel opportunity for parasite control?
Authors: Irvine Allister , Huws Sharon A. , Atkinson Louise E. , Mousley Angela 
Published: September 2022

AbstractAntimicrobial Peptides (AMPs) are key constituents of the invertebrate innate immune system where they provide critical protection against microbial threat. Knowledge of AMP complements within phylum Nematoda is limited however nematodes adopt diverse life strategies and frequently reside in microbe-rich environments such that they are likely possess broad AMP profiles with bioactivity against a range of microbiota. Indeed, parasitic nematode AMPs likely have roles in defence against invading pathogens and modulation of the host microbiome.In this study the distribution and abundance of AMP-encoding genes were examined in 134 nematode genomes providing the most comprehensive profile of AMPs within phylum Nematoda. We reveal that phylum Nematoda is AMP-rich and -diverse, where 5887 genes encode AMPs. Genome and transcriptome analyses broadly reveal: (i) AMP family profiles that are influenced by nematode lifestyle where free-living nematodes appear to have an expansion of AMPs relative to parasitic species; (ii) major differences in the AMP profiles between nematode clades where Clade 9/V and 10/IV species possess expanded AMP repertoires; (iii) AMP families with highly restricted profiles (e.g. Cecropins and Diapausins) and others [e.g. Nemapores and Glycine Rich Secreted Peptides (GRSPs)] which are more widely distributed; (iv) complexity in the distribution and abundance of Defensin subfamily members; and (v) expression of AMPs in key nematode life stages.These data indicate that phylum Nematoda has a diverse array of AMPs and underscores the need to interrogate AMP function to unravel their importance to nematode biology and host-worm-microbiome interactions. Enhanced understanding of the Nematode Antimicrobial Peptidome will inform drug discovery pipelines for pathogen control.
A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease
Authors: Avanzato Victoria A. , Bushmaker Trenton , Oguntuyo Kasopefoluwa Y. , Yinda Kwe Claude , Duyvesteyn Helen M. E. , Stass Robert , Meade-White Kimberly , Rosenke Rebecca , Thomas Tina , Saturday Greg , Doores Katie J. , Lee Benhur , Bowden Thomas A. , Munster Vincent J. 
Published: September 2022

AbstractNipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the fab region bound to NiV-F (NiV-F–Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offered complete protection from NiV disease, demonstrating beneficial activity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.
Continuous transcriptome analysis reveals novel patterns of early gene expression in Drosophila embryos
Authors: Pérez-Mojica J. Eduardo , Enders Lennart , Walsh Joseph , Lau Kin H. , Lempradl Adelheid 
Published: September 2022

ABSTRACTEarly organismal development consists of transformative events that lay the foundation for body formation and long-term phenotype. Despite this understanding, the rapid progression of events and the limited material available are major barriers to studying the earliest stages. The size and accessibility of Drosophila embryos overcome some of these limitations, and several studies characterizing early transcriptional events have been reported. Unfortunately, manual embryo staging, and elaborate protocols make the techniques employed in these studies prone to human and technical errors and incompatible with routine laboratory use. Herein, we present a straight-forward and operationally simple methodology for studying the early transcription (≤3 hours) in Drosophila. This method relies on single-embryo RNA-sequencing and transcriptome ordering along a developmental trajectory (pseudo-time), thereby avoiding the need for the staging of the embryos. The obtained high-resolution and time-sensitive mRNA expression profiles uncovered the exact onset of transcription and degradation of transcripts and revealed an earlier transcription start for several zygotic genes. In addition, degradation patterns suggest that maternal mRNA decay is independent of mRNA levels. By classifying each embryo as male or female, we were also able to study sex-biased transcription between the beginning of zygotic transcription to gastrulation and identified 120 differentially expressed mRNAs. Using sex-specific transcription signatures, embryos can be sexed directly, eliminating the need for Y-chromosome genotyping. Herein, we report an accessible, single-embryo sequencing approach for high-resolution, time-sensitive transcriptome analysis. Our data provide an unparalleled resolution of gene expression during early development and enhance the current understanding of early transcriptional processes.
Prototyping of a lateral flow assay based on monoclonal antibodies for detection of Bothrops venoms
Authors: Knudsen Cecilie , Jürgensen Jonas A. , Knudsen Pelle D. , Oganesyan Irina , Harrison Julian A. , Dam Søren H. , Haack Aleksander M. , Friis Rasmus U. W. , Belfakir Selma B. , Ross Georgina M. S. , Zenobi Renato , Laustsen Andreas H. 
Published: September 2022

AbstractBackgroundBrazil is home to a multitude of venomous snakes, perhaps the most medically relevant of which belong to the Bothrops genus. Bothrops spp. are responsible for roughly 70% of all snakebites in Brazil, and envenomings caused by their bites can be treated with three types of antivenom: bothropic antivenom, bothro-lachetic antivenom, and bothro-crotalic antivenom. The choice in antivenom that is administered depends not only on its availability and how certain the treating physician is that the patient was bitten by a bothropic snake. The diagnosis of a bothropic envenoming can be made based on expert identification of a photo of the snake or based on a syndromic approach wherein the clinician examines the patient for characteristic manifestations of envenoming. This approach can be very effective but requires staff that has been trained in clinical snakebite management, which, unfortunately, far from all relevant staff has.ResultsIn this paper, we describe a prototype of the first lateral flow assay (LFA) capable of detecting venoms from Brazilian Bothrops spp. The monoclonal antibodies for the assay were generated using hybridoma technology and screened in sandwich enzyme-linked immunosorbent assays (ELISAs) to identify Bothrops spp. specific antibody sandwich pairs. The sandwich pairs were used to develop a prototype LFA that was able to detect venom from several different Bothrops spp. The limit of detection (LoD) of the prototype was evaluated using Brazilian B. atrox whole venom and was determined to be 8.0 ng/mL in spiked serum samples and 9.5 ng/mL in spiked urine samples, when using a portable reader, and < 25 ng/mL in spiked buffer when reading by eye.SignificanceThe work presented here serves as a proof of concept of a genus-specific venom detection kit, which could support physicians in diagnosing Bothrops envenomings. Although further optimization and testing is needed before the LFA can find clinical use, such a device could aid in decentralizing antivenoms in the Brazilian Amazon and help ensure optimal snakebite management for even more victims of this highly neglected disease.
Residual Complex I activity supports glutamate catabolism and mtSLP via canonical Krebs cycle activity during acute anoxia without OXPHOS
Authors: Ravasz Dora , Bui David , Nazarian Sara , Pallag Gergely , Karnok Noemi , Roberts Jennie , Tennant Daniel A , Greenwood Bennett , Kitayev Alex , Hill Collin , Komlódi Timea , Doerrier Carolina , Gnaiger Erich , Kiebish Michael A , Raska Alexandra , Kolev Krasimir , Czumbel Bence , Narain Niven R , Seyfried Thomas N , Chinopoulos Christos 
Published: September 2022

ABSTRACTAnoxia halts oxidative phosphorylation (OXPHOS) causing an accumulation of reduced compounds in mitochondrial matrix which impedes dehydrogenases. By simultaneously measuring oxygen concentration, NADH autofluorescence, mitochondrial membrane potential and ubiquinone reduction extentin organelloin real-time, we show that Complex I utilized endogenous quinones to oxidize NADH under acute anoxia. Untargeted or [U-13C]glutamate-targeted metabolomic analysis of matrix and effluxed metabolites extracted during anoxia in the presence or absence of site-specific inhibitors of the electron transfer system inferred that NAD+regenerated by Complex I is reduced by the 2-oxoglutarate dehydrogenase complex yielding succinyl-CoA supporting mitochondrial substrate-level phosphorylation (mtSLP), releasing succinate. Yet, targeted metabolomic analysis using [U-13C]malate also revealed concomitant succinate dehydrogenase reversal during anoxia yielding succinate by reducing fumarate, albeit to a small extent. Our results highlight the importance of quinone availability to Complex I oxidizing NADH, thus maintaining glutamate catabolism and mtSLP in the absence of OXPHOS.
EEG-neurofeedback for promoting neuromodulation in the elderly: evidence from a double-blind study
Authors: Andrade Katia , Guieysse Thomas , Razafimahatratra Solofo , Houmani Nesma , Klarsfeld André , Dreyfus Gérard , Dubois Bruno , Medani Takfarinas , Vialatte François 
Published: September 2022

AbstractBackgroundElectroencephalography (EEG) is a non-invasive method that records the brain signals with time resolution in the millisecond range, thereby allowing the monitoring of subjects’ mental states in real time. Using appropriate biomarkers extracted from these EEG signals and presenting them back in a neurofeedback loop can foster neural compensation mechanisms by teaching subjects to modulate their brain activity. Over the last decades, several neural biomarkers of aging have been described, with growing evidence suggesting that neuromodulation may have an important role in regulating brain activity in the elderly.Methods and objectivesWe used three neural biomarkers of aging, namely the Peak Alpha Frequency, the Gamma-band synchronization, and the Theta/Beta ratio, in the framework of an EEG-based brain-computer interface, with two main objectives: 1) to test whether healthy elderly people with subjective memory complaints may learn to modulate their brain activity through EEG-neurofeedback training in a double-blind, placebo-controlled study; and 2) whether that neuromodulation may have a positive impact on subjects’ cognition.ResultsA significant self-modulation of two neural biomarkers that usually decline with age was observed exclusively in the group of subjects who underwent the EEG-neurofeedback training, in clear contrast with the subjects who received the sham feedback. This neuromodulation did not have a direct effect on subjects’ cognitive abilities, as measured by neuropsychological tests pre-versus post-training, probably because all the subjects accurately performed these tests already at study entry (i.e., pre-training).ConclusionThe results of this double-blind study are in line with one of the main criteria for successful neuromodulation, thus encouraging research on EEG-neurofeedback as a promising non-pharmacological intervention for promoting self-regulation of brain activity with a view to improve cognitive aging.
CRISPR/Cas9 mediated gene editing in non-model nematodePanagrolaimussp. PS1159
Authors: Hellekes Viktoria , Claus Denise , Seiler Johanna , Illner Felix , Schiffer Philipp H. , Kroiher Michael 
Published: September 2022

AbstractThe phylum Nematoda harbors a huge diversity of species in a broad range of ecosystems and habitats. Nematodes share a largely conserved Bauplan but major differences have been found in early developmental processes. The development of the nematode model organismCaenorhabditis eleganshas been studied in great detail for decades. These efforts have provided the community with a large number of protocols and methods. Unfortunately, many of these tools are not easily applicable in non-Caenorhabditisnematodes. In recent years it has become clear that many crucial genes in theC. elegansdevelopmental toolkit are absent in other nematode species. It is thus necessary to study the developmental program of other nematode species in detail to understand evolutionary conservation and novelty in the phylum.Panagrolaimussp. PS1159 is a non-parasitic nematode exhibiting parthenogenetic reproduction and we are establishing the species to comparatively study evolution, biodiversity and alternative reproduction and survival strategies. Here, we demonstrate the first successful application of the CRISPR/Cas9 system for genome editing inPanagrolaimussp. PS1159 and its closely related hermaphroditic speciesPropanagrolaimussp. JU765 with both the non-homologous end joining and the homology-directed repair mechanism. Using microinjections and modifying published protocols fromC. elegans and P. pacificuswe induced mutations in the orthologue ofunc-22, which resulted in a visible uncoordinated twitching phenotype. We also compared the HDR efficiency following the delivery of different repair templates. This work will expand the applicability for a wide range of non-model nematodes from across the tree and facilitate functional analysis into the evolution of parthenogenesis, changes in the developmental program of Nematoda, and cryptobiosis.
Genetic Variation in Chromatin State Across Multiple Tissues inDrosophila melanogaster
Authors: Huynh Khoi , Smith Brittny R. , Macdonald Stuart J. , Long Anthony D. 
Published: September 2022

ABSTRACTWe use ATAC-seq to examine chromatin accessibility for four different tissues inDrosophila melanogaster: adult female brain, ovaries, and both wing and eye-antennal imaginal discs from males. Each tissue is assayed in eight different inbred strain genetic backgrounds, seven associated with a reference quality genome assembly. We develop a method for the quantile normalization of ATAC-seq fragments and test for differences in coverage among genotypes, tissues, and their interaction at 44099 peaks throughout the euchromatic genome. For the strains with reference quality genome assemblies, we correct ATAC-seq profiles for read mis-mapping due to nearby polymorphic structural variants (SVs). Comparing coverage among genotypes without accounting for SVs results in a highly elevated rate (55%) of identifying false positive differences in chromatin state between genotypes. After SV correction, we identify 1050, 30383, and 4508 regions whose peak heights are polymorphic among genotypes, among tissues, or exhibit genotype-by-tissue interactions, respectively. Finally, we identify 3988 candidate causative variants that explain at least 80% of the variance in chromatin state at nearby ATAC-seq peaks.AUTHOR SUMMARYChromatin states are well described inDrosophila melanogasterembryos, but adult and pre-adult tissues are poorly studied, as are differences among genotypes. We carried out ATAC-seq on four different tissues in eight different inbred genotypes with biological replicates within tissue and genotype. We discover that apparent differences in coverage, and by inference chromatin openness, are often due to segregating structural variants (SVs) that can only be corrected for if strains are associated with high-quality genome assemblies. After correction for false positives associated with SVs, we identify thousands of regions that appear to vary in chromatin state between genotypes or vary between genotypes in a tissue-dependent manner. It has been widely speculated thatcis-regulatory variants contribute to standing variation in complex traits. If this is true, chromatin states that vary between individuals, perhaps in a tissue-dependent manner, are likely to be enriched for quantitative trait loci.
Impact of non-proteinogenic amino acid norvaline and proteinogenic valine misincorporation on a secondary structure of a model peptide
Authors: Škibola Zara , Sovulj Ita Gruić , Maršavelski Aleksandra 
Published: September 2022

ABSTRACTNorvaline is a straight-chain, hydrophobic, non-proteinogenic amino acid, isomeric with valine. Both amino acids can be misincorporated into proteins at isoleucine positions by isoleucyl-tRNA synthetase when the mechanisms of translation fidelity are impaired. Our previous study showed that proteome-wide substitution of isoleucine with norvaline resulted in higher toxicity in comparison to the proteome-wide substitution of isoleucine with valine. Although mistranslated proteins/peptides are considered to have non-native structures responsible for their toxicity, the observed difference in protein stability between norvaline and valine misincorporation has not yet been fully understood. To examine the observed effect, we choose the model peptide with three isoleucines in the native structure, introduced selected amino acids at isoleucine positions and applied molecular-dynamics simulations at different temperatures. The obtained results showed that norvaline has the highest destructive effect on the β-sheet structure and suggest that the higher toxicity of norvaline over valine is predominantly due to the misincorporation within the β-sheet secondary elements.