bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shotgun metagenomics unravels higher antibiotic resistome profile in Bangladeshi gut microbiome
Authors: Bhattacharjee Arittra , Jamal Tabassum Binte , Ahammad Ishtiaque , Chowdhury Zeshan Mahmud , Rahman Anisur , Dewan Gourab , Talukder Shiny , Hossain Mohammad Uzzal , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md 
Published: March 2023

AbstractAntibiotic resistance management is a challenging task in Low and Middle-Income Countries (LMICs) such as Bangladesh. Improper regulation and uncontrolled spreading of Antibiotic Resistant Genes (ARGs) from LIMCs pose a great threat to global public health. The human gut microbiome is a massive reservoir of Antibiotic Resistant Genes (ARGs). In this study, we unraveled the ARGs in the gut microbiome of the Bangladeshi population and compared them with several other countries around the world. Here, 31 fecal samples from different ethnic groups living in Bangladesh namely Bengali (n=9), Chakma (n=6), Khyang (n=5), Marma (n=6), and Tripura (n=5) were collected. Shotgun metagenomic sequencing method was implemented for revealing the ARGs. The resistome profiling was executed on three levels-the total microbiome, the plasmidome, and the virome. In all three levels, samples from Bangladeshi cohorts showed higher ARG profiles compared to foreign samples. On average, the number of ARGs in the Bangladeshi samples ranged between 75.11 and 88. Among them, class C beta-lactamases, quinolone resistance genes, and tetracycline efflux pumps were relatively more abundant. Additionally, the MexPQ-OpmE drug resistance pathway was found to be more prevalent. Findings from our study suggest that the spread of antibiotic resistance within the Bangladeshi population is being facilitated by the gut microbiome especially via the mobilome. Therefore, strict regulation on antibiotic usage is necessary to halt the spread of ARGs.
First insights into theAurelia auritatranscriptome response upon manipulation of its microbiome
Authors: Weiland-Bräuer Nancy , Koutsouveli Vasiliki , Langfeldt Daniela , Schmitz Ruth A. 
Published: March 2023

AbstractThe associated diverse microbiome contributes to the overall fitness ofAurelia aurita, particularly to asexual reproduction. However, howA. auritamaintains this specific microbiome or reacts to manipulations is unknown. In this report, the response ofA. auritato manipulations of its native microbiome was studied by a transcriptomics approach. Microbiome-manipulated polyps were generated by antibiotic treatment and challenging polyps with a non-native, native, and potentially pathogenic bacterium. Total RNA extraction followed by RNAseq resulted in over 155 million reads used for ade novoassembly. The transcriptome analysis showed that the antibiotic-induced change and resulting reduction of the microbiome significantly affected the host transcriptome, e.g., genes involved in processes related to immune response and defense mechanisms were highly upregulated. Similarly, manipulating the microbiome by challenging the polyp with a high load of bacteria (2 × 107cells/polyp) resulted in induced transcription of apoptosis-, defense-, and immune response genes. A second focus was on host-derived quorum sensing interference as a potential defense strategy. Quorum Quenching (QQ) activities and the respective encoding QQ-ORFs ofA. auritawere identified by functional screening a cDNA-based expression library generated inEscherichia coli. Corresponding sequences were identified in the transcriptome assembly. Moreover, gene expression analysis revealed differential expression of QQ genes depending on the treatment, strongly suggesting QQ as an additional defense strategy. Overall, this study allows first insights intoA. aurita’sresponse to manipulating its microbiome, thus paving the way for an in-depth analysis of the basal immune system and additional fundamental defense strategies.
Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes
Authors: Gonçalves Luciana Mateus , Fahd Qadir Mirza Muhammad , Boulina Maria , Makhmutova Madina , Almaça Joana 
Published: March 2023

AbstractPancreatic islets are endocrine organs that depend on their microvasculature to function properly. Along with endothelial cells, pericytes comprise the islet microvascular network. These mural cells are crucial for microvascular stability and function, but it is not known if/how they are affected during the development of type 1 diabetes (T1D). Here we investigated islet pericyte density, phenotype and function using living pancreas slices from donors without diabetes, donors with a single T1D-associated autoantibody (Aab+; all GADA+) and recent onset T1D cases. Our data show that islet pericyte and capillary responses to vasoactive stimuli are impaired early on in T1D. Microvascular dysfunction is associated with a switch in the phenotype of islet pericytes towards pro-fibrotic myofibroblasts. Using publicly available RNAseq data, we further found that transcriptional alterations related to endothelin-1 signaling, vascular and ECM remodeling are hallmarks of single Aab+ donor pancreata. Our data show that islet pericyte/microvascular dysfunction is present at early stages of islet autoimmunity.HighlightsChanges in islet pericyte coverage and phenotype occur during T1D progression.Vascular responses to vasoactive stimuli are impaired in islets from Aab+ and T1D donors.Endothelin-1 action and receptor expression are altered in vascular cells from Aab+ and T1D donors.Strong vascular remodeling occurs in the pancreas of Aab+ and T1D donors.
Impact of Post-Translational Modification on MHC Peptide Binding and TCR Engagement
Authors: Kelly Joey J. , Bloodworth Nathaniel , Shao Qianqian , Shabanowitz Jeffery , Hunt Donald , Meiler Jens , Pires Marcos M. 
Published: March 2023

AbstractThe human major histocompatibility complex (MHC) plays a crucial role in the presentation of peptidic fragments from proteins; these peptides can be derived from self-proteins or from non-human antigens, such as those produced by viruses or bacteria. To prevent cytotoxicity against healthy cells, thymocytes expressing T cell receptors (TCRs) that recognize self-peptides are removed from circulation in a process called negative selection. However, post-translational modifications (PTMs) are largely excluded from negative selection; this feature opens the door to the possibility that PTMs directly contribute to the development of autoreactive T cells and subsequent autoimmune diseases. Despite it being well-established that PTMs are prevalent in peptides presented on MHCs, the exact mechanisms by which PTMs influence the antigen presentation machinery remains poorly understood. In our work, we introduce chemical modifications mirroring PTMs onto peptides to systematically investigate their impact on MHC binding and TCR recognition. Our findings reveal the numerous ways PTMs alter antigen presentation, which could have implications for tumor neoantigen presentation.
Sleep Deprivation, Sleep Fragmentation and Social Jet Lag increase temperature preference inDrosophila
Authors: Roach S Tanner , Ford Melanie C , Simhambhatla Vikram , Loutrianakis Vasilios , Farah Hamza , Li Zhaoyi , Periandri Erica M. , Abdalla Dina , Huang Irene , Kalra Arjan , Shaw Paul J. 
Published: March 2023

AbstractDespite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of sleep, but does not activate sleep homeostatic mechanisms nor induce impairments in short-term memory also resulted in flies choosing warmer temperatures. To identify the underlying neuronal circuits, we used RNAi to knock down the receptor forPigment dispersing factor, a peptide that influences circadian rhythms, temperature preference and sleep. Expressing UAS-PdfrRNAiin subsets of clock neurons prevented sleep fragmentation from increasing temperature preference. Finally, we evaluated temperature preference after flies had undergone a social jet lag protocol which is known to disrupt clock neurons. In this protocol, flies experience a 3 h light phase delay on Friday followed by a 3 h light advance on Sunday evening. Flies exposed to social jet lag exhibited an increase in temperature preference which persisted for several days. Our findings identify specific clock neurons that are modulated by sleep disruption to increase temperature preference. Moreover, our data indicate that temperature preference may be a more sensitive indicator of sleep disruption than learning and memory.
Multimodal neural correlates of childhood psychopathology
Authors: Royer Jessica , Kebets Valeria , Piguet Camille , Chen Jianzhong , Ooi Leon Qi Rong , Kirschner Matthias , Siffredi Vanessa , Misic Bratislav , Yeo B.T. Thomas , Bernhardt Boris C. 
Published: March 2023

AbstractComplex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with thepfactor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples, supporting generalizability, and robust to variations in analytical parameters. Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.
Identification of novel buffering mechanisms in aortic arch artery development and congenital heart disease
Authors: Ramirez AnnJosette , Vyzas Christina A. , Zhao Huaning , Eng Kevin , Degenhardt Karl , Astrof Sophie 
Published: March 2023

RationaleThe resiliency of embryonic development to genetic and environmental perturbations has been long appreciated; however, little is known about the mechanisms underlying the robustness of developmental processes. Aberrations resulting in neonatal lethality are exemplified by congenital heart disease (CHD) arising from defective morphogenesis of pharyngeal arch arteries (PAA) and their derivatives.ObjectiveTo uncover mechanisms underlying the robustness of PAA morphogenesis.Methods and ResultsThe second heart field (SHF) gives rise to the PAA endothelium. Here, we show that the number of SHF-derived ECs is regulated byVEGFR2andTbx1. Remarkably, when SHF-derived EC number is decreased, PAA development can be rescued by the compensatory endothelium. Blocking such compensatory response leads to embryonic demise. To determine the source of compensating ECs and mechanisms regulating their recruitment, we investigated three-dimensional EC connectivity, EC fate, and gene expression. Our studies demonstrate that the expression of VEGFR2 by the SHF is required for the differentiation of SHF-derived cells into PAA ECs. The deletion of one VEGFR2 allele (VEGFR2SHF-HET) reduces SHF contribution to the PAA endothelium, while the deletion of both alleles (VEGFR2SHF-KO) abolishes it. The decrease in SHF-derived ECs in VEGFR2SHF-HETand VEGFR2SHF-KOembryos is complemented by the recruitment of ECs from the nearby veins. Compensatory ECs contribute to PAA derivatives, giving rise to the endothelium of the aortic arch and the ductus in VEGFR2SHF-KOmutants. Blocking the compensatory response in VEGFR2SHF-KOmutants results in embryonic lethality shortly after mid-gestation. The compensatory ECs are absent inTbx1+/-embryos, a model for 22q11 deletion syndrome, leading to unpredictable arch artery morphogenesis and CHD.Tbx1regulates the recruitment of the compensatory endothelium in an SHF-non-cell-autonomous manner.ConclusionsOur studies uncover a novel buffering mechanism underlying the resiliency of PAA development and remodeling.Nonstandard Abbreviations and Acronyms in Alphabetical OrderCHD – congenital heart disease; ECs – endothelial cells; IAA-B – interrupted aortic arch type B; PAA – pharyngeal arch arteries; RERSA – retro-esophageal right subclavian artery; SHF – second heart field; VEGFR2 – Vascular endothelial growth factor receptor 2.
A co-transcriptional ribosome assembly checkpoint controls nascent large ribosomal subunit maturation
Authors: Sanghai Zahra A. , Piwowarczyk Rafal , Broeck Arnaud Vanden , Klinge Sebastian 
Published: March 2023

AbstractDuring transcription of eukaryotic ribosomal DNA in the nucleolus, assembly checkpoints exist that guarantee the formation of stable precursors of small and large ribosomal subunits. While the formation of an early large subunit assembly checkpoint precedes the separation of small and large subunit maturation, its mechanism of action and function remain unknown. Here, we report the cryo-electron microscopy structure of the co-transcriptional large ribosomal subunit assembly intermediate that serves as a checkpoint. The structure provides the mechanistic basis for how quality control pathways are established through co-transcriptional ribosome assembly factors, that structurally interrogate, remodel, and together with ribosomal proteins cooperatively stabilize correctly folded pre-ribosomal RNA. Our findings thus provide a molecular explanation for quality control during eukaryotic ribosome assembly in the nucleolus.
Genomic transcription factor binding site selection is edited by the chromatin remodeling factor CHD4
Authors: Saotome Mika , Poduval Deepak Balakrishnan , Grimm Sara A. , Nagornyuk Aerica , Gunarathna Sakuntha , Shimbo Takashi , Wade Paul A. , Takaku Motoki 
Published: March 2023

AbstractBiologically precise enhancer licensing by lineage-determining transcription factors enables activation of transcripts appropriate to biological demand and prevents deleterious gene activation. This essential process is challenged by the millions of matches to most transcription factor binding motifs present in many eukaryotic genomes, leading to questions about how transcription factors achieve the exquisite specificity required. The importance of chromatin remodeling factors to enhancer activation is highlighted by their frequent mutation in developmental disorders and in cancer. Here we determine the roles of CHD4 to enhancer licensing and maintenance in breast cancer cells and during cellular reprogramming. In unchallenged basal breast cancer cells, CHD4 modulates chromatin accessibility at transcription factor binding sites; its depletion leads to altered motif scanning and redistribution of transcription factors to sites not previously occupied. During GATA3-mediated cellular reprogramming, CHD4 activity is necessary to prevent inappropriate chromatin opening and enhancer licensing. Mechanistically, CHD4 competes with transcription factor-DNA interaction by promoting nucleosome positioning over binding motifs. We propose that CHD4 acts as a chromatin proof-reading enzyme that prevents inappropriate gene expression by editing binding site selection by transcription factors.
Sleep interventions for adults admitted to psychiatric inpatient settings: a systematic scoping review
Authors: Aboaja Anne M. , Dewa Lindsay H. , Perry Amanda E. , Carey Jon F. , Steele Rachel , Abdelsamie Ahmed , Alhasan Gies T. A. , Sharma Ishwari S. , Cairney Scott A. 
Published: March 2023

AbstractSleep disturbances are common, affecting over half of adults with a mental disorder. For those admitted to a psychiatric ward, difficulties with sleep are compounded by factors relating to the inpatient setting. We conducted a scoping review of sleep intervention studies on adults admitted to psychiatric settings. We categorised the different types of sleep interventions and identified the effects on sleep and other health outcomes. Instruments used to measure sleep were also described. The search strategy yielded 2530 studies, of which 20 met the inclusion criteria. There was evidence of more non-pharmacological than pharmacological interventions having been tested in inpatient settings. Results indicated that non-pharmacological interventions based on cognitive behaviour therapy for insomnia improve sleep and may improve mental and physical health. Several distinct sleep measures were used in the studies. Objective sleep measures were not commonly used. Gaps in the literature were identified, highlighting the importance of research into a wider range of sleep interventions tested against a control using objective measures of sleep with evaluation of additional mental and physical health outcomes among adults in the psychiatric inpatient settings.
Brain rhythms control microglial response and cytokine expression via NFκB signaling
Authors: Prichard Ashley , Garza Kristie M. , Shridhar Avni , He Christopher , Bitfaran Sara , Wang Yunmiao , Goodson Matthew C. , Jaeger Dieter , Wood Levi B. , Singer Annabelle C. 
Published: March 2023

AbstractMicroglia, the brain’s primary immune cells, transform in response to changes in sensory or neural activity, like sensory deprivation. However, little is known about how specific frequencies of neural activity, or brain rhythms, impact microglia and cytokine signaling. Using visual noninvasive flickering sensory stimulation (flicker) to induce electrical neural activity at different frequencies, 40Hz, within the gamma band and 20Hz, within the beta band, we discovered these brain rhythms differentially affect microglial morphology and cytokine expression in healthy animals. We found that flicker induced expression of certain cytokines, including IL-10 and M-CSF, that was independent of microglia. Because NFκB is activated by synaptic activity and regulates cytokines, we hypothesized this pathway plays a causal role in frequency-specific cytokine and microglial responses. Indeed, we found that after flicker, phospho-NFκB co-labeled with neurons more than microglia. Furthermore, inhibition of NFκB signaling by a small molecule inhibitor down-regulated flicker-induced cytokine expression and attenuated flicker-induced changes in microglia morphology. These results reveal a new mechanism through which brain rhythms affect brain function by altering microglia morphology and cytokines via NFκB.TeaserFrequency-specific brain rhythms regulate cytokine expression, microglia morphology, and microglia-independent expression of M-CSF and IL10 via NFκB.
Genomic repeat landscape evolution across the teleost fish lineages
Authors: Reinar William B , Tørresen Ole K , Nederbragt Alexander J , Matschiner Michael , Jentoft Sissel , Jakobsen Kjetill S 
Published: March 2023

AbstractRepetitive DNA make up a considerable fraction of most eukaryotic genomes. In fish, transposable element (TE) activity have coincided with rapid species diversification. Here, we annotated the repetitive content in 100 genome assemblies, covering the major branches of the diverse lineage of teleost fish. We investigated if TE content correlates with family level net diversification rates and found support for a weak negative correlation. Further, we found that TE content, the degree of parental care and short tandem repeat (STR) content contributed to genome size variability. In contrast to TEs, STR content showed a negative relationship with genome size. STR content did not correlate with TE content, which implies independent evolutionary paths. Last, marine and freshwater fish have large differences in STR content. The most extreme propagation was found in the genomes of codfish species and Atlantic herring. Such a high density of STRs is likely to increase the mutational load, which we propose could be counterbalanced by high fecundity as seen in codfishes and herring.
An integrated workflow for quantitative analysis of the newly synthesized proteome
Authors: Borteçen Toman , Müller Torsten , Krijgsveld Jeroen 
Published: March 2023

AbstractThe analysis of proteins that are newly synthesized upon a cellular perturbation can provide detailed insight in the proteomic response that is elicited by specific cues. This can be investigated by pulse-labeling of cells with clickable and stable-isotope-coded amino acids for enrichment and mass spectrometric characterization of newly synthesized proteins (NSPs), however convoluted protocols prohibit their routine application. Here we optimized multiple steps in sample preparation, mass spectrometry and data analysis, and integrated them in a semi-automated workflow for the quantitative analysis of the newly synthesized proteome (QuaNPA). Reduced input requirements and data-independent acquisition (DIA) enabled analysis of triple-SILAC-labeled NSP samples, with enhanced throughput while featuring high quantitative accuracy. We applied QuaNPA to investigate the time-resolved cellular response to interferon-gamma (IFNg), observing rapid induction of known and novel targets 2h after IFNg treatment. QuaNPA provides a powerful approach for large-scale investigation of NSPs to gain insight in complex cellular processes.
A bile metabolite atlas reveals infection-triggered interorgan mediators of intestinal homeostasis and defense
Authors: Zhang Ting , Hasegawa Yuko , Waldor Matthew K. 
Published: March 2023

AbstractAn essential function of the liver is the formation of bile. This aqueous solution is critical for fat absorption and is transported to the duodenum via the common bile duct. Despite extensive studies of bile salts, other components of bile are less well-charted. Here, we characterized the murine bile metabolome and investigated how the microbiota and enteric infection influence bile composition. We discovered that the bile metabolome is not only substantially more complex than appreciated but is dynamic and responsive to the microbiota and enteric infection. Hepatic transcriptomics identified enteric infection-triggered pathways that likely underlie bile remodeling. Enteric infections stimulated elevation of four dicarboxylates in bile that modulated intestinal gut epithelial and microbiota composition, inflammasome activation, and host defense. Our data suggest that enteric infection-associated signals are relayed between the intestine and liver and induce transcriptional programs that shape the bile metabolome, modifying bile’s immunomodulatory and host defense functions.