bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic data reveal divergent paths of chitinase evolution underlying dietary convergence in anteaters and pangolins
Authors: Allio Rémi , Teullet Sophie , Lutgen Dave , Magdeleine Amandine , Koual Rachid , Tilak Marie-Ka , de Thoisy Benoit , Emerling Christopher A. , Lefébure Tristan , Delsuc Frédéric 
Published: November 2022

AbstractAnt-eating mammals represent a textbook example of convergent evolution. Among them, anteaters and pangolins exhibit the most extreme convergent phenotypes with complete tooth loss, elongated skulls, protruding tongues, hypertrophied salivary glands producing large amounts of saliva, and powerful claws for ripping open ant and termite nests. However, comparative genomic analyses have shown that anteaters and pangolins differ in their chitinase acidic gene (CHIA) repertoires, which potentially degrade the chitinous exoskeletons of ingested ants and termites. While the southern tamandua (Tamandua tetradactyla) harbors four functionalCHIAparalogs (CHIA1-4), Asian pangolins (Manisspp.) have only one functional paralog (CHIA5). Here, we performed a comparative transcriptomic analysis of salivary glands in 33 placental species, including 16 novel transcriptomes from ant-eating species and close relatives. Our results suggest that salivary glands play an important role in adaptation to an insect-based diet, as expression of differentCHIAparalogs is observed in insectivorous species. Furthermore, convergently-evolved pangolins and anteaters express different chitinases in their digestive tracts. In the Malayan pangolin,CHIA5is overexpressed in all major digestive organs, whereas in the southern tamandua, all four functional paralogs are expressed, at very high levels forCHIA1andCHIA2in the pancreas, and forCHIA3andCHIA4in the salivary glands, stomach, liver, and pancreas. Overall, our results demonstrate that divergent molecular mechanisms within the chitinase acidic gene family underlie convergent adaptation to the ant-eating diet in pangolins and anteaters. This study highlights the role of historical contingency and molecular tinkering of the chitin-digestive enzyme toolkit in this classic example of convergent evolution.
Environmental changes associated with drying climate are expected to affect functional groups of pro- and microeukaryotes differently in temporary saline waters
Authors: Márton Zsuzsanna , Szabó Beáta , Vad Csaba F. , Pálffy Károly , Horváth Zsófia 
Published: November 2022

AbstractTemporary ponds are among the most sensitive aquatic habitats to climate change. Their microbial communities have crucial roles in food webs and biogeochemical cycling, yet how their communities are assembled along environmental gradients is still understudied. This study aimed to reveal the environmental drivers of diversity (OTU-based richness, evenness, and phylogenetic diversity) and community composition from a network of saline temporary ponds, soda pans, in two consecutive spring seasons characterized by contrasting weather conditions. We used DNA-based molecular methods to investigate microbial community composition. We tested the effect of environmental variables on the diversity of prokaryotic (bacteria, cyanobacteria) and microeukaryotic functional groups (ciliates, heterotrophic flagellates and nanoflagellates, fungi, phytoplankton) within and across the years. Conductivity and the concentration of total suspended solids and phosphorus were the most important environmental variables affecting diversity patterns in all functional groups. Environmental conditions were harsher and they also had a stronger impact on community composition in the dry spring. Our results imply that these conditions, which are becoming more frequent with climate change, have a negative effect on microbial diversity in temporary saline ponds. This eventually might translate into community-level shifts across trophic groups with changing local conditions with implications for ecosystem functioning.
The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation inClostridioides difficile
Authors: Auria Emile , Hunault Lise , England Patrick , Monot Marc , Da Fonseca Juliana Pipoli , Matondo Mariette , Duchateau Magalie , Tremblay Yannick D.N. , Dupuy Bruno 
Published: November 2022

AbstractThe ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms.Clostridioides difficileinfections have a high rate of recurrence and relapses and it is hypothesised that biofilms are involved in its pathogenicity and persistence. Biofilm formation byC. difficileis still poorly understood. It has been shown that specific molecules such as deoxycholate (DCA) or metronidazole induce biofilm formation, but the mechanisms involved remain elusive. In this study, we describe the role of theC. difficilelipoprotein CD1687 during DCA-induced biofilm formation. We showed that the expression ofCD1687, which is part of an operon within theCD1685-CD1689gene cluster, is controlled by multiple transcription starting sites and some are induced in response to DCA. Only CD1687 is required for biofilm formation and the overexpression of CD1687 is sufficient to induce biofilm formation. Using RNAseq analysis, we showed that CD1687 affects the expression of transporters and metabolic pathways and we identified several potential binding partners by pull-down assay, including transport-associated extracellular proteins. We then demonstrated that CD1687 is surface exposed inC. difficile, and that this localization is required for DCA-induced biofilm formation. Given this localization and the fact thatC. difficileforms eDNA-rich biofilms, we confirmed that CD1687 binds DNA in a non-specific manner. We thus hypothesize that CD1687 is a component of the downstream response to DCA leading to biofilm formation by promoting interaction between the cells and the biofilm matrix by binding eDNA.
The Loci of Insect Phenotypic Evolution
Authors: Courtier-Orgogozo Virginie 
Published: November 2022

AbstractInsects are important elements of terrestrial ecosystems because they pollinate plants, destroy crops, transmit diseases to livestock and humans, and are important components of food chains. Here I used Gephebase, a manually curated database of genetic variants associated with natural and domesticated trait variation, to explore current knowledge about the genes and the mutations known to contribute to natural phenotypic variation in insects. Analysis of over 600 mutations reveals that data are concentrated towards certain species and traits and that experimental approaches have changed over time. The distribution of coding and cis-regulatory changes varies with traits, experimental approaches and identified gene loci. Recent studies highlight the important role of standing variation, repeated mutations in hotspot genes, recombination, inversions, and introgression.HighlightsGephebase compiles more than 600 genes and mutations contributing to insect natural variationOur genetic knowledge is biased towards certain traits and insect speciesExperimental approaches and studied insect species have changed over the yearsThe relative distribution of coding and cis-regulatory mutations varies with traits and genesClusters of causal mutations are more frequently found in insects than in other organisms
Wet Adhesive Hydrogels to Correct Malacic Trachea (Tracheomalacia): A Proof of Concept
Authors: Uslu Ece , Rana Vijay Kumar , Anagnostopoulos Sokratis , Karami Peyman , Bergadano Alessandra , Courbon Cecile , Gorostidi Francois , Sandu Kishore , Stergiopulos Nikolaos , Pioletti Dominique P. 
Published: November 2022

AbstractTracheomalacia (TM) is a condition in which the anterior part of the trachea consisting of cartilage and/or the posterior part consisting muscle are too soft to ensure its mechanical support. This situation may result in an excessive and potentially lethal collapse of the airway in the newborns. Current treatment techniques include tracheal reconstruction, tracheoplasty, endo- and extraluminal stents, but are all facing important limitations.To reduce the shortcomings of actual TM treatments, this work proposes a new strategy by wrapping an adhesive hydrogel patch extraluminally around a malacic trachea. To validate this approach, first a numerical model revealed that a hydrogel patch with sufficient mechanical and adhesion strength can potentially preserve the trachea’s physiological shape. Accordingly, a new hydrogel formulation was synthesized employing the hydroxyethyl acrylamide (HEAam) and polyethylene glycol methacrylate (PEGDMA) as main polymer network and crosslinker, respectively. These hydrogels provide excellent adhesion on wet tracheal surfaces, thanks to a two-step photo-polymerization approach. Ex vivo experiments revealed that the developed adhesive hydrogel patches can restrain the collapsing of malacic trachea under applied negative pressure. This study, to be confirmed by in vivo studies, is open to the possibility of a new treatment in the difficult clinical situation of tracheomalacia in newborns.
Computation-guided redesign of promoter specificity of a bacterial RNA polymerase
Authors: Liu Xiangyang , Meger Anthony T. , Gillis Thomas , Raman Srivatsan 
Published: November 2022

ABSTRACTThe ability to regulate circuits and pathways is central to cellular control. The existing toolkit is predominantly comprised of local transcription regulators that are unsuitable for exerting control at a global genome-wide scale. Bacterial sigma factors are ideal global regulators as they direct the RNA polymerase to thousands of transcription sites. Here, we redesigned the promoter specificity of theE. colihousekeeping sigma factor, sigma-70, toward five orthogonal promoter targets not recognized by the native sigma-70. These orthogonal sigma-70s were engineered by screening a pooled library of computationally-guided designs customized toward each promoter target. A combination of conserved interactions with the DNA backbone and target-specific interactions facilitate new promoter recognition. Activity of the top performing redesigned sigma-70s varied across the promoter targets and ranged from 17% to 77% of native sigma-70 on its canonical active promoter. These orthogonal sigma factors represent a new suite of regulators for global transcriptional control.
Quantification of adulterated fox-derived components in meat Products by Drop Digital Polymerase Chain Reaction
Authors: Wang Hui , Chen Chen , Xu Miaomiao , Zhang Yan , Chen Boxu , Li Yongyan , Jia Wenshen , Chen Jia , Zhou Wei 
Published: November 2022

AbstractThere are still large research gaps in the testing standards for non-edible meat-derived components at present. Here we report a novel approach to quantification of adulterated fox-derived components in meat products by drop digital polymerase chain reaction(ddPCR). It was better to identify the adulteration that has been added either inadvertently or deliberately during the process by designing single primers on housekeeping genes. In this paper, the fox meat was used as the experimental materials and the relationship between sample quality and copy number was established by extracting DNA and using DNA concentration as an intermediary. The results of ddPCR showed that both the relationships between meat weight and DNA concentration and between DNA concentration and DNA copy number (C) were nearly linear within the dynamic range. The DNA concentration was utilized as an intermediate value to establish the formulae about the relationship between the original meat weight and DNA copy number: Mfox=0.05C+2.7. The method’s feasibility was validated using artificial adulteration of different proportions The establishment of this method provides technical support for relevant regulatory authorities to monitor the adulteration of fox meat.
Enhancing single-cell proteomics through tailored Data-Independent Acquisition and micropillar array-based chromatography
Authors: Petrosius Valdemaras , Aragon-Fernandez Pedro , Üresin Nil , Phlairaharn Teeradon , Furtwängler Benjamin , de Beeck Jeff op , Thomsen Simon Francis , auf dem Keller Ulrich , Porse Bo T. , Schoof Erwin M. 
Published: November 2022

AbstractSingle-cell resolution analysis of complex biological tissues is fundamental to capture cell-state heterogeneity and distinct cellular signaling patterns that remain obscured with population-based techniques. The limited amount of material encapsulated in a single cell however, raises significant technical challenges to molecular profiling. Due to extensive optimization efforts, mass spectrometry-based single-cell proteomics (scp-MS) has emerged as a powerful tool to facilitate proteome profiling from ultra-low amounts of input, although further development is needed to realize its full potential. To this end, we carried out comprehensive analysis of orbitrap-based data independent acquisition (DIA) for limited material proteomics. Notably, we found a fundamental difference between optimal DIA methods for high- and low-load samples. We further improved our low-input DIA method by relying on high-resolution MS1 quantification, thus more efficiently utilizing available mass analyzer time. With our ultra-low input tailored DIA method, we were able to accommodate long injection times and high resolution, while keeping the scan cycle time low enough to ensure robust quantification. Finally, we establish a complete experimental scp-MS workflow, combining DIA with accessible single-cell sample preparation and the latest chromatographic and computational advances and showcase our developments by profiling real single cells.
Identifying eukaryotes in drinking water metagenomes and factors influencing their biogeography
Authors: Gabrielli Marco , Dai Zihan , Delafont Vincent , Timmers Peer , van der Wielen Paul , Antonelli Manuela , Pinto Ameet 
Published: November 2022

AbstractThe biogeography of eukaryotes in drinking water systems is poorly understood relative to prokaryotes or viruses. A common challenge with studying complex eukaryotic communities from natural and engineered systems is that the metagenomic analysis workflows are currently not as mature as those that focus on prokaryotes or even viruses. In this study, we benchmarked different strategies to recover eukaryotic sequences and genomes from metagenomic data and applied the best-performing workflow to explore eukaryotic communities present in drinking water distribution systems (DWDSs). We developed an ensemble approach that exploits k-mer and reference-based strategies to improve eukaryotic sequence identification from metagenomes and identified MetaBAT2 as the best performing binning approach for clustering of eukaryotic sequences. Applying this workflow on the DWDSs metagenomes showed that eukaryotic sequences typically constituted a small proportion (i.e., <1%) of the overall metagenomic data. Eukaryotic sequences showed higher relative abundances in surface water-fed and chlorine disinfected systems. Further, the alpha and beta-diversity of eukaryotes were correlated with prokaryotic and viral communities. Finally, a co-occurrence analysis highlighted clusters of eukaryotes whose presence and abundance in DWDSs is affected by disinfection strategies, climate conditions, and source water types.SynopsisAfter benchmarking tools and developing a dedicated consensus workflow for eukaryotic sequence detection in metagenomes, the experimental, environmental, and engineering factors affecting their biogeography in drinking water distribution systems were investigatedGraphical abstract
Type I IFN signaling mediates NET release to promoteMycobacterium tuberculosisreplication and granuloma caseation
Authors: Chowdhury Chanchal Sur , Kinsella Rachel L. , Nehls E. Michael , Naik Sumanta K. , Lane Daniel S. , Talukdar Priyanka , Chavez Sthefany M. , Smirnov Asya , Beatty Wandy , Kreamalmeyer Darren , Mattila Joshua T. , Stallings Christina L. 
Published: November 2022

SUMMARYNeutrophils are the most abundant cell type in airways of tuberculosis patients. Recent investigations reported induction of neutrophil extracellular traps (NETs) duringMycobacterium tuberculosis(Mtb) infection, however, the molecular regulation and impact of NETosis onMtbpathogenesis is unknown. We find that in response toMtbinfection in neutrophils, PAD4 citrullinates histones to decondense chromatin that gets packaged into vesicles for release as NETs in a manner that can maintain neutrophil viability and promoteMtbreplication. Type I interferon, which has been associated with NETosis in numerous contexts but without a known mechanism, promotes formation of chromatin-containing vesicles and NET release. Analysis of nonhuman primate granulomas supports a model where neutrophils are exposed to type I interferon from macrophages as they migrate into the granuloma, where they release NETs that contribute to necrosis and caseation. Our data reveals NETosis as a promising target to inhibitMtbreplication and granuloma caseation.
Identifying common genes, proteins, and pathways from human miRNA and gene blood profiles in multiple sclerosis patients
Authors: Chakraborty Souvik , Maiti Tarasankar , Bhowmick Sushmita , Sarkar Soumili 
Published: November 2022

AbstractThe molecular pathway associated with Multiple sclerosis (MS) is complex and symptomatic treatments are only available right now. Early diagnosis of MS creates a window for healthcare providers to manage the disease more efficiently. Blood-based biomarker study has been done in the past to identify the upregulated and downregulated genes but in this present study, a novel approach has been taken for identifying genes associated with the disease. In this present study, hub genes are identified and the top ten hub genes were used to identify drugs associated with them. Upregulated genes were identified using the dataset GSE21942 (which contains information related to genes identified in the blood of multiple sclerosis patients) and datasets GSE17846 and GSE61741(which contains information related to microRNAs taken from multiple sclerosis patients). Genes associated with microRNAs were identified using miRWalk. Common genes from both miRWalk and the dataset GSE21942 were identified and were subjected to STRINGdb for the creation of a protein-protein interaction network and this network was then imported to Cytoscape for identifying the top ten hub genes. The top ten hub genes were subjected to EnrichR for enrichment analysis of genes. In our study, it was found that CTNNB1 is the gene with the highest degree (116).
Proteomic profiling identifies biomarkers of COVID-19 severity
Authors: Harriott Noa C. , Ryan Amy L. 
Published: November 2022

Abstract/SummarySARS-CoV-2 infection remains a major public health concern, particularly for the aged and those individuals with co-morbidities at risk for developing severe COVID-19. Understanding the pathogenesis and biomarkers associated with responses to SARS-CoV-2 infection remain critical components in developing effective therapeutic approaches, especially in cases of severe and long-COVID-19. In this study blood plasma protein expression was compared in subjects with mild, moderate, and severe COVID-19 disease. Evaluation of an inflammatory protein panel confirms upregulation of proteins including TNFβ, IL-6, IL-8, IL-12, already associated with severe cytokine storm and progression to severe COVID-19. Importantly, we identify several proteins not yet associated with COVID-19 disease, including mesothelin (MSLN), that are expressed at significantly higher levels in severe COVID-19 subjects. In addition, we find a subset of markers associated with T-cell and dendritic cell responses to viral infection that are significantly higher in mild cases and decrease in expression as severity of COVID-19 increases, suggesting that an immediate and effective activation of T-cells is critical in modulating disease progression. Together, our findings identify new targets for further investigation as therapeutic approaches for the treatment of SARS-CoV-2 infection and prevention of complications of severe COVID-19.
Epidemiological impact of a large number of incorrect negative SARS-CoV-2 test results in South West England during September and October 2021
Authors: Hounsome L. , Herr D. , Bryant R. , Smith R. , Loman L. , Harris J. , Youhan U. , Dzene E. , Hadjipantelis P. , Long H. , Laurence T. , Riley S. , Cumming F. 
Published: November 2022

AbstractBackgroundIn England, free testing for COVID-19 was widely available from early in the pandemic until 1 April 2022. Based on apparent differences in the rate of positive PCR tests at a single laboratory compared to the rest of the laboratory network, we hypothesised that a substantial number of UK PCR tests processed during September and October 2021 may have been incorrectly reported as negative, compared with the rest of the laboratory network. We investigate the epidemiological impact of this incident.MethodsWe estimate the additional number of COVID-19 cases that would have been reported had the sensitivity of the laboratory test procedure not dropped for the period 2 September to 12 October. In addition, by making comparisons between the most affected local areas and comparator populations, we estimate the number of additional infections, cases, hospitalisations and deaths that could have occurred as a result of increased transmission due to the misclassification of tests.ResultsWe estimate that around 39,000 tests may have been incorrectly classified during this period and, as a direct result of this incident, the most affected areas in the South West could have experienced between 6,000 and 34,000 additional reportable cases, with a central estimate of around 24,000 additional reportable cases. Using modelled relationships between key variables, we estimate that this central estimate could have translated to approximately 55,000 additional infections, which means that each incorrect negative test likely led to just over two additional infections. In those same geographical areas, our results also suggest an increased number of admissions and deaths.ConclusionThe incident is likely to have had a measurable impact on cases and infections in the affected areas in the South West of England.
DAPTEV: Deep aptamer evolutionary modelling for COVID-19 drug design
Authors: Andress Cameron , Kappel Kalli , Cuperlovic-Culf Miroslava , Yan Hongbin , Li Yifeng 
Published: November 2022

AbstractTypical drug discovery and development processes are costly, time consuming and often biased by expert opinion. Aptamers are short, single-stranded oligonucleotides (RNA/DNA) that bind to target proteins and other types of biomolecules. Compared with small-molecule drugs, aptamers can bind to their targets with high affinity (binding strength) and specificity (uniquely interacting with the target only). The conventional development process for aptamers utilizes a manual process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX), which is costly, slow, dependent on library choice and often produces aptamers that are not optimized. To address these challenges, in this research, we create an intelligent approach, named DAPTEV, for generating and evolving aptamer sequences to support aptamer-based drug discovery and development. Using the COVID-19 spike protein as a target, our computational results suggest that DAPTEV is able to produce structurally complex aptamers with strong binding affinities.Author summaryCompared with small-molecule drugs, aptamer drugs are short RNAs/DNAs that can specifically bind to targets with high strength. With the interest of discovering novel aptamer drugs as an alternative to address the long-lasting COVID-19 pandemic, in this research, we developed an artificial intelligence (AI) framework for the in silico design of novel aptamer drugs that can prevent the SARS-CoV-2 virus from entering human cells. Our research is valuable as we explore a novel approach for the treatment of SARS-CoV-2 infection and the AI framework could be applied to address future health crises.