bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass lysis of bacterial predators drives the enrichment of antibiotic resistance in soil microbial communities
Authors: Saha Saheli , Kalathera Jyotsna , Sumi Thoniparambil Sunil , Mane Vishwadeep , Zimmermann Sina , Waschina Silvio , Pande Samay 
Published: November 2023

AbstractWhile studies on anthropogenic activities and antibiotic resistance are numerous, the impact of microbial interactions on resistance in complex communities remains uncertain. Here we demonstrate a correlation between the presence ofMyxococcus xanthusin natural soil communities and the abundance of antibiotic-resistant bacteria. Further, introducingM. xanthusisolates also enriches antibiotic resistance. This is due to the mass lysis ofM. xanthuscells, which results in a toxic environment that fosters the proliferation of pre-existing resistant bacteria rather than de novo resistance evolution. Metagenomic analysis revealed that this enrichment is not limited to the tested antibiotics in culture-based methods, indicating its broader relevance. Crucially, these findings go beyond laboratory settings, showingM. xanthusintroduction enriches resistant isolates in natural soil communities. Finally, we demonstrate that the mass lysis ofM. xanthuscells during starvation-induced development—key aspect of the lifecycle ofM. xanthus—also results in the enrichment of antibiotic resistance in soil communities. Together, we demonstrate how life-history traits in bacterial predators, likeM. xanthus, significantly impact antibiotic resistomes in nature. This study also highlights the complex dynamics at play in the evolution and maintenance of antibiotic resistance, emphasizing the role of interspecies interactions in shaping antibiotic resistance profiles.
Statistical Methods for Microrheology of Airway Mucus with Extreme Heterogeneity
Authors: Caughman Neall , Papanikolas Micah , Markovetz Matthew , Freeman Ronit , Hill David B. , Forest M. Gregory , Lysy Martin 
Published: November 2023

AbstractThe mucus lining of the human airway epithelium contains two gel-forming mucins, MUC5B and MUC5AC. During progression of cystic fibrosis (CF), mucus hyper-concentrates as its mucin ratio changes, coinciding with formation of insoluble, dense mucus flakes. We explore rheological heterogeneity of this pathology with reconstituted mucus matching three stages of CF progression and particle-tracking of 200 nm and 1 micron diameter beads. We introduce statistical data analysis methods specific to low signal-to-noise data within flakes. Each bead time series is decomposed into: (i) a fractional Brownian motion (fBm)classifier of the pure time-series signal; (ii) high-frequency static and dynamic noise; and (iii) low-frequency deterministic drift. Subsequent analysis focuses on the denoised fBm classifier ensemble from each mucus sample and bead diameter. Every ensemble fails a homogeneity test, compelling clustering methods to assess levels of heterogeneity. The first binary level detects beads within vs. outside flakes. A second binary level detects within-flake bead signals that can vs. cannot be disentangled from the experimental noise floor. We show all denoised ensembles, within- and outside-flakes, fail a homogeneity test, compelling additional clustering; next, all clusters with sufficient data fail a homogeneity test. These levels of heterogeneity are consistent with outcomes from a stochastic phase-separation process, and dictate applying the generalized Stokes-Einstein relation to each bead per cluster per sample, then frequency-domain averaging to assess rheological heterogeneity. Flakes exhibit a spectrum of gel-like and sol-like domains, outside-flake solutions a spectrum of sol-like domains, painting a rheological signature of the phase-separation process underlying flake-burdened mucus.
RNA sequencing demonstratesex vivoneocortical transcriptomic changes induced by epileptiform activity in male and female mice
Authors: Vaughan Alec J. , McMeekin Laura J. , Hine Kutter , Stubbs Isaac W. , Codadu Neela K. , Cockell Simon , Hill Jonathon T. , Cowell Rita , Trevelyan Andrew J , Parrish R. Ryley 
Published: November 2023

AbstractSeizures are generally associated with epilepsy but may also be a symptom of many other neurological conditions. A hallmark of a seizure is the intensity of the local neuronal activation, which can drive large-scale gene transcription changes. Such changes in the transcriptional profile are likely to alter neuronal function, thereby contributing to the pathological process. Therefore, there is a strong clinical imperative to characterie how gene expression is changed by seizure activity. To this end, we developed a simplifiedex vivotechnique for studying seizure-induced transcriptional changes. We compared the RNA sequencing profile in mouse neocortical tissue that had up to 3 hours of epileptiform activity induced by 4-aminopyridine (4AP), relative to control brain slices not exposed to the drug. We identified over 100 genes with significantly altered expression after 4AP treatment, including multiple genes involved in MAPK, TNF, and neuroinflammatory signalling pathways, all of which have been linked to epilepsy previously. Notably, the patterns in male and female brain slices were almost identical. Various immediate early genes were among those showing the largest upregulation. The set of down-regulated genes included ones that might be expected either to increase or to decrease neuronal excitability. In summary, we found the seizure-induced transcriptional profile to be complex, but the changes aligned well with an analysis of published epilepsy-associated genes. We discuss how simple models may provide new angles for investigating seizure-induced transcriptional changes.Significance StatementIt is well-established that strong neuronal activation results in large-scale transcriptomic changes. Understanding this process is of particular importance in epilepsy, which is characterized by paroxysmal pathological discharges. The complexity ofin vivoactivity patterns, however, present many difficulties for interpretation of the transcriptional changes. In contrast,ex vivoseizure models provide better experimental control and quantification of activity patterns, with lower welfare impact. Importantly, we now show that these models also replicate the transcriptional patterns previously reported in chronic human and animal epilepsy, thus validating their use in these kinds of study.
Unravelling the molecular mechanisms of fish salinity adaptation in the face of multiple stressors: A comparative multi-tissue transcriptomic study in the Llobregat River, Barcelona, Spain
Authors: Escobar-Sierra Camilo , Cañedo-Argüelles Miguel , Vinyoles Dolors , Lampert Kathrin P. 
Published: November 2023

AbstractFreshwater salinization poses a growing global environmental concern, introducing complex chemical cocktails and jeopardizing freshwater biodiversity, particularly fish populations. This research aimed to elucidate the molecular foundations of salinity adaptation in a non-native minnow species (Phoxinus septimaniaexP. dragarum) exposed to saline effluents from potash mines in the Llobregat River, Barcelona, Spain. Employing high-throughput mRNA sequencing and differential gene expression analyses, we examined brain, gills, and liver tissues collected from fish at two stations (upstream and downstream of saline effluent discharge). Salinization markedly influenced global gene expression profiles, with the brain exhibiting the most differentially expressed genes, emphasizing its unique sensitivity to salinity fluctuations. Pathway analyses revealed the expected enrichment of ion transport and osmoregulation pathways across all tissues. Furthermore, tissue-specific pathways associated with stress, reproduction, growth, immune responses, methylation, and neurological development were identified in the context of salinization. Rigorous validation of RNA-seq data through quantitative PCR (qPCR) underscored the robustness and consistency of our findings across platforms. This investigation unveils intricate molecular mechanisms steering salinity adaptation in non-native minnows confronting diverse environmental stressors. Advancing our comprehension of genomic responses to salinity changes, our study provides crucial insights into the adaptive strategies of aquatic organisms grappling with freshwater salinization. This comprehensive analysis sheds light on the underlying genetic and physiological mechanisms governing fish adaptation in salinity-stressed environments, offering essential knowledge for the conservation and management of freshwater ecosystems facing escalating salinization pressures.
Neural correlates of modality-specific and modality-invariant object recognition in the perirhinal cortex
Authors: Lim Heung-Yeol , Lee Inah 
Published: November 2023

SummaryThe perirhinal cortex (PER) supports multimodal object recognition, but how multimodal information of objects is integrated within the PER remains unknown. Here, we recorded single units within the PER while rats performed a PER-dependent multimodal object-recognition task. In this task, audiovisual cues were simultaneously (multimodally) or separately (unimodally) presented. We identified two types of object-selective neurons in the PER: crossmodal cells, showing constant firing patterns for an object irrespective of its modality, and unimodal cells, showing a preference for a specific modality. Unimodal cells further dissociated unimodal and multimodal versions of the object by modulating their firing rates according to the modality condition. A population-decoding analysis confirmed that the PER could perform both modality-invariant and modality-specific object decoding – the former for recognizing an object as the same in various conditions and the latter for remembering modality-specific experiences of the same object.
Phenotypic memory in quorum sensing
Authors: Ostovar Ghazaleh , Boedicker James Q. 
Published: November 2023

AbstractQuorum sensing (QS) is a regulatory mechanism used by bacteria to coordinate group behavior in response to high cell densities. During QS, cells monitor the concentration of external signals, known as autoinducers, as a proxy for cell density. QS often involves positive feedback loops, leading to the upregulation of genes associated with QS signal production and detection. This results in distinct steady-state concentrations of QS-related molecules in QS-ON and QS-OFF states. Due to the slow decay rates of biomolecules such as proteins, even after removal of the initial stimuli, cells can retain elevated levels of QS-associated biomolecules for extended periods of time. This persistence of biomolecules after the removal of initial stimuli has the potential to impact the response to future stimuli, denoting a memory of past exposure. This phenomenon, which is a consequence of the carry-over of biomolecules rather than genetic inheritance, is known as “phenotypic” memory.This theoretical study aims to investigate the presence of phenotypic memory in QS and the conditions that influence this memory. Numerical simulations based on ordinary differential equations and analytical modeling were used to study gene expression in response to sudden changes in cell density and extracellular signal concentrations. The model examined the effect of various cellular parameters on the strength of QS memory and the impact on gene regulatory dynamics. The findings revealed that QS memory has a transient effect on the expression of QS-responsive genes. These consequences of QS memory depend strongly on how cell density was perturbed, as well as various cellular parameters, including the Fold Change in the expression of QS-regulated genes, the autoinducer synthesis rate, the autoinducer threshold required for activation, and the cell growth rate.Author summaryBacteria use a mechanism known as quorum sensing (QS) to collaborate when their numbers are high. Cells produce and detect signals that trigger the production of certain proteins and changes in cell behavior. Interestingly, the molecules produced during this process can linger even after the initial signal is gone. The persistence of these molecules is a form of “memory”, as cells are temporarily changed by events in the recent past. Our theoretical study focuses on exploring this memory and the factors that influence it. To do this, we used simulations and models to examine how history of exposure to signals can affect the future response of cells. We found that the prior exposure to signals can influence how bacteria respond in the future, but this memory only has consequences under specific conditions. This research contributes to our understanding of quorum sensing and how bacteria adapt to environmental changes.
The HtrA chaperone monitors sortase-assembled pilus biogenesis inEnterococcus faecalis
Authors: Yong Adeline M.H. , Winter Cristina Colomer , Chong Kelvin K. L. , Gao Iris Hanxing , Matysik Artur , Chen Swaine L. , Kline Kimberly A. 
Published: November 2023

AbstractSortase-assembled pili contribute to virulence in many Gram-positive bacteria. InEnterococcus faecalis, the endocarditis and biofilm-associated pilus (Ebp) is polymerized on the membrane by sortase C (SrtC) and attached to the cell wall by sortase A (SrtA). In the absence of SrtA, polymerized pili remain anchored to the membrane (i.e. off-pathway). Here we show that the high temperature requirement A (HtrA) bifunctional chaperone/protease ofE. faecalisis a quality control system that clears aberrant off-pathway pili from the cell membrane. In the absence of HtrA and SrtA, accumulation of membrane-bound pili leads to cell envelope stress and partially induces the regulon of the ceftriaxone resistance-associated CroRS two-component system, which in turn causes hyper-piliation and cell morphology alterations. Inactivation ofcroRin the ΔsrtAΔhtrAbackground partially restores the observed defects of the ΔsrtAΔhtrAstrain, supporting a role for CroRS in the response to membrane perturbations. Moreover, absence of SrtA and HtrA decreases basal tolerance ofE. faecalisagainst cephalosporins and daptomycin. The link between HtrA, pilus biogenesis and the CroRS two-component system provides new insights into theE. faecalisresponse to endogenous membrane perturbations.Author summaryTo explore the role of the HtrA chaperone/protease inE. faecalisoff-pathway pilus clearance, we deletedhtrAin anE. faecalisOG1RF ΔsrtAstrain known to retain polymerized pili on the cell membrane. Cells in the ΔsrtAΔhtrAbackground are hyper-piliated, possess altered morphology, and are more susceptible to cell envelope-targeting antibiotics as compared to the parent OG1RF strain. RNA sequencing of the ΔsrtAΔhtrAstrain revealed transcriptional changes reminiscent of a membrane stress response. This response was pilus-dependent and contained several members of the CroR regulon. Inactivation of the response regulator CroR in the ΔsrtAΔhtrAbackground restored (at least partially) piliation and cell morphology but not antibiotic susceptibility, linking CroR for the first time to pilus biogenesis and endogenous cell envelope stress.
The nematode (Ascaris suum) intestine is a location of synergistic anthelmintic effects of Cry5B and levamisole
Authors: Williams Paul D. E. , Brewer Matthew T. , Aroian Raffi , Robertson Alan P. , Martin Richard J. 
Published: November 2023

AbstractA novel group of biocidal compounds are the Crystal 3D (Cry) and Cytolytic (Cyt) proteins produced byBacillus thuringiensis(Bt). Some Bt Cry proteins have a selective nematocidal activity, with Cry5B being the most studied. Cry5B kills nematode parasites by binding selectively to membrane glycosphingolipids, then forming pores in the cell membranes of the intestine leading to damage. Cry5B selectively targets multiple species of nematodes from different clades and has no effect against mammalian hosts. Levamisole is a cholinomimetic anthelmintic that acts by selectively opening L-subtype nicotinic acetylcholine receptor ion-channels (L-AChRs) that have been found on muscles of nematodes. A synergistic nematocidal interaction between levamisole and Cry5B has been described previously, but the location, mechanism and time-course of this synergism is not known. In this study we follow the timeline of the effects of levamisole and Cry5B on the Ca2+levels in enterocyte cells from the intestine ofAscaris suumusing fluorescence imaging. The peak Ca2+responses to levamisole were observed after approximately 10 minutes while the peak responses to activated Cry5B were observed after approximately 80 minutes. When levamisole and Cry5B were applied simultaneously, we observed that the responses to Cry5B were bigger and occurred sooner than when it was applied by itself. It is proposed that there is an irreversible cytoplasmic Ca2+overload that leads to necrotic cell-death in the enterocyte that is induced by levamisole opening Ca2+permeable L-subtype nAChRs and the development of Ca2+permeable Cry5B toxin pores in enterocyte plasma membranes. The effects of levamisole potentiate and speed the actions of Cry5B.
Whole-genome sequencing of major malaria vectors revealed an evolution of new insecticide resistance variants in a longitudinal study in Burkina Faso
Authors: Kientega Mahamadi , Clarkson Chris S , Traoré Nouhoun , Hui Tin-Yu J , O’Loughlin Samantha , Millogo Abdoul-Azize , Epopa Patric S , Yao Franck A , Belem Adrien M G , Brenas Jon , Miles Alistair , Burt Austin , Diabaté Abdoulaye 
Published: November 2023

AbstractIntensive deployment of insecticide based malaria vector control tools results in the rapid evolution of phenotypes resistant to these chemicals. Understanding this process on the genomic level is essential for the deployment of successful interventions. Using whole genome sequencing data of 1409 individualAn. Gambiaes.l. collected from 2012 to 2017, we investigated the change in genetic structure and the evolution of the insecticide resistance variants in natural populations over time and space. The results showed similar and constant nucleotide diversity and negative Tajima’s D betweenAn. gambiaes.s. andAn. coluzzii. PCA andFSTshowed a clear genetic structure in theAn. gambiaes.l. species. Genome-wideFSTand H12 scans identified genomic regions under divergent selection and also having an implication in the adaptations to ecological changes. Novel voltage-gated sodium channel pyrethroid resistance target-site alleles (V402L, I1527T) were identified at increasing frequencies alongside the establishedkdralleles (Vgsc-L995F,Vgsc-L995SandN1570Y) within theAn. gambiaes.l. populations. Organophosphate metabolic resistance markers were also identified, at increasing frequencies, within theAn. gambiaes.s. populations from 2012 to 2017, including the SNPAce1-G280Sand its associated duplication. Variants simultaneously identified in the same vector populations raise concerns about the long-term efficacy of new-generation bednets and the recently introduced organophosphate pirimiphos-methyl indoor residual spraying. These findings highlighted the benefit of genomic malaria vector surveillance for the detection of new insecticide resistance variants, the monitoring of the existing resistance variants, and also to get insights into the evolutionary processes driving insecticide resistance.Author SummaryGenomic surveillance of malaria vectors is crucial for understanding the genetic variation in natural vector populations and also guiding the implementation of novel and innovative vector control tools. Application of sequencing technologies in vector studies provide insights on the genetic and evolutionary phenomena of vectors that could have impact on vector control strategies. By analyzing the whole genome data of 1409 wildAn. gambiaes.l. mosquito collected between 2012 and 2017, we showed an emergence of novel insecticide resistance markers alongside increasing frequencies of existing insecticide resistance variants over time in Burkina Faso. We showed the benefit of genomic surveillance of malaria vectors for the monitoring of the insecticide resistance variants and also providing insights into the evolutionary processes driving insecticide resistance.
Comprehensive Codon Usage Analysis Across Diverse Plant Lineages
Authors: Majeed Aasim , Rehman Wahid Ul , Kaur Amitozdeep , Das Sreemoyee , Joseph Josepheena , Singh Amandeep , Bhardwaj Pankaj 
Published: November 2023

AbstractThe variation of codon usage patterns in response to the evolution of organisms is an intriguing question to answer. The purpose of this study was to investigate the relevance of the evolutionary events of vascularization and seed production with the codon usage patterns in different plant lineages. We found that the optimal codons of non-vascular lineages generally end with GC, whereas those of the vascular lineages end with AU. Correspondence analysis and model-based clustering showed that the evolution of the codon usage pattern follows the evolutionary event of the vascularization more precisely than that of the seed production. The dinucleotides CpG and TpA were under-represented in all the lineages, whereas the dinucleotide TpG was found over-represented in all the lineages, except algae. Evolutionary-related lineages showed similar codon pair bias (CPB). The dinucleotide CpA showed a similar representation as those of its parent codon pairs. Although natural selection predominates over mutational pressure in determining the codon usage bias (CUB), the relative influence of mutational pressure is higher in the non-vascular lineages than in the vascular lineages.
Design of Worst-Case-Optimal Spaced Seeds
Authors: Rahmann Sven , Zentgraf Jens 
Published: November 2023

AbstractRead mapping (and alignment) is a fundamental problem in biological sequence analysis. For speed and computational efficiency, many popular read mappers tolerate only a few differences between the read and the corresponding part of the reference genome, which leads to reference bias: Reads with too many difference are not guaranteed to be mapped correctly or at all, because to even consider a genomic position, a sufficiently longexactmatch (seed) must exist.While pangenomes and their graph-based representations provide one way to avoid reference bias by enlarging the reference, we explore an orthogonal approach and consider stronger substitution-tolerant primitives, namelyspaced seedsor gappedk-mers. Given two integersk ≤ w, one considerskselected positions, described by amask, from each length-wwindow in a sequence. In the existing literature, masks with certainprobabilisticguarantees have been designed for small values ofk.Here, for the first time, we take a combinatorial approach from aworst-caseperspective. For any mask, using integer linear programs, we find least favorable distributions of sequence changes in two different senses: (1) minimizing the number of unchanged windows; (2) minimizing the number of positions covered by unchanged windows. Then, among all masks of a given shape (k, w), we find the set of best masks that maximize these minima. As a result, we obtain highly robust masks, even for large numbers of changes. Their advantages are illustrated in two ways: First, we provide a new challenge dataset of simulated DNA reads, on which current methods like bwa-mem2, minimap2, or strobealign struggle to find seeds, and therefore cannot produce alignments against the human t2t reference genome, whereas we are able to find the correct location from a few unique spaced seeds. Second, we use real DNA data from the highly diverse human HLA region, which we are able to map correctly based on a few exactly matching spaced seeds of well-chosen masks, without evaluating alignments.