bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation and Genetic Architecture of Major Depressive Disorder Subgroups Defined by Weight and Sleep Changes
Authors: Marshall Sally , Adams Mark J , Evans Kathryn L , Strawbridge Rona J , Campbell Archie , Hayward Caroline , McIntosh Andrew , Thomson Pippa 
Published: September 2022

AbstractMajor depressive disorder, MDD, is highly heterogeneous and thus subgroups with different underlying aetiologies have been postulated. The aim of this work is to further characterise depression subgroups defined using sleep and weight changes. Probable lifetime MDD cases (n = 26,662) from the UK Biobank were stratified into three subgroups defined by self-reported weight and sleep changes during worst episode: (i) increased weight and sleep (↑WS), (ii) decreased weight and sleep (↓WS) and (iii) the remaining uncategorised individuals. Analyses compared the depression characteristics, mental health scores, neurological and inflammatory comorbidities and genetic architecture between subgroups and with 50,147 controls from UK Biobank. In contrast to ↑WS depression, ↓WS depression had a higher age of onset and lower proportion reporting countless or continuous episodes compared to uncategorised individuals. The ↓WS depression also had a higher wellbeing score than the other subgroups. Analyses of subgroup comorbidities identified a novel association between ↑WS depression and epilepsy. Subgroup-specific GWAS identified three genome-wide significant loci associated with ↑WS in genes previously associated with immunometabolic traits and response to anticonvulsants. The effect of BMI adjustment in the genetic analyses of the subgroups and using broader weight-only definitions were also examined. The findings provide further evidence for differences in the characteristics and genetic architecture of depression subgroups defined by sleep and weight change and highlight the importance of dividing non-↑WS individuals into ↓WS and uncategorised subgroups in analyses, as ↓WS symptoms may identify a more acute depression subgroup.
Prognostic association of immunoproteasome expression in solid tumours is governed by the immediate immune environment
Authors: Kumar Rahul , Dhaka Bhavya , Sahoo Sarthak , Jolly Mohit Kumar , Sabarinathan Radhakrishnan 
Published: September 2022

AbstractInduction of immunoproteasome (IP) expression in tumour cells can enhance antigen presentation and immunogenicity. Recently, overexpression of IP genes has been associated with better prognosis and response to immune checkpoint blockade (ICB) therapies in melanoma. However, the extent of this association in other solid tumour types and how that is influenced by tumour cell-intrinsic and cell-extrinsic factors remains unclear. Here, we address this by exploring the gene expression patterns from available bulk and single-cell transcriptomic data of primary tumours. We find that IP expression positively correlates with the constitutive proteasome (CP) across multiple tumour types. Furthermore, tumours with high IP expression exhibit cytotoxic immune cell infiltration and upregulation of interferon-gamma and TNF-α pathways in tumour cells. However, the association of IP expression with overall survival (in TCGA cohort) and response to ICB therapy (in non-TCGA cohorts) is tumour-type specific and is greatly influenced by immune cell infiltration patterns. This emphasises the need for considering immune cell infiltration patterns, along with IP expression, to be used as a prognostic biomarker to predict overall survival or response to ICB treatment in solid tumours, besides melanoma.
Cryo-EM structures of the Mycobacterium 50S subunit reveal an intrinsic conformational dynamics of 23S rRNA helices
Authors: Baid Priya , Sengupta Jayati 
Published: September 2022

AbstractPathogenic organisms encounter a broad range of stress conditions within host micro-environment and adopt variety of mechanisms to stall protein translation and protect translational machinery. Structural investigations of the ribosomes isolated from pathogenic and non-pathogenic Mycobacterium species have identified several mycobacteria-specific structural features of ribosomal RNA and proteins. Here, we report a growth phase-dependent conformational switch of domain III and IV helices (H54a and H67-H71) of the mycobacterium 23S rRNA. Cryo-electron microscopy (cryo-EM) structures (∼3-4 Å) of the M. smegmatis (Msm) 50S ribosomal subunit of log-phase manifested that, while H68 possesses the usual stretched conformation in one of the maps, another one exhibits an unprecedented conformation of H68 curling onto a differently oriented H69, indicating an intrinsic dynamic nature of H68. Remarkably, a 2.8Å cryo-EM map of the Msm stationary-state 50S subunit unveiled that H68 preferably acquires folded conformation in this state (closely mimicking dormant state). Formation of a bulge-out structure by H68 at the inter-subunit surface of the stationary-state 50S subunit due to the rRNA conformational changes prevents association with 30S subunit and keeps an inactive pool of the 50S subunit representing a ribosome-protection mechanism during dormancy. Evidently, this dynamic nature of H68 is an integral part of the cellular functions of mycobacterium ribosome, and irreversibly arresting H68 flexible motion would stall ribosome function. Thus, this conformational change may be exploited to develop anti-mycobacterium drug molecules.Significant statementBacteria utilize several mechanisms to reprogram the protein synthesis machinery so that their metabolism is reduced in the dormant state. Mycobacteria are capable of hiding themselves in a dormant state during physiological stresses. Our study identified a hitherto-unknown folded conformation of the helix 68 (H68) of domain IV of mycobacterial 23S rRNA, which is predominantly present in the stationary state (closely mimicking latency). Our results suggest that this conformational transition is instrumental in keeping an inactive pool of the 50S subunit in the stationary state. Irreversibly arresting such conformational dynamics would lead to protein synthesis shutdown in mycobacteria during dormancy. Thus, this folded conformation of H68 offers an excellent therapeutic intervention site to treat mycobacterial latent infection.HighlightsIdentification of a hitherto-unknown folded conformation of the helix 68 of mycobacterial 23S rRNAH68 conformation transition represents a new ribosome protection mechanism in dormant mycobacteriaThe conformational switch of mycobacterial H68 offers an excellent therapeutic intervention site
The seeker R package: simplified fetching and processing of transcriptome data
Authors: Schoenbachler Joshua L. , Hughey Jacob J. 
Published: September 2022

AbstractTranscriptome data have become invaluable for interrogating biological systems. Preparing a transcriptome dataset for analysis, particularly an RNA-seq dataset, entails multiple steps and software programs, each with its own command-line interface (CLI). Although these CLIs are powerful, they often require shell scripting for automation and parallelization, which can have a high learning curve, especially when the details of the CLIs vary from one tool to another. However, many individuals working with transcriptome data are already familiar with R due to the plethora and popularity of R-based tools for analyzing biological data. Thus, we developed an R package called seeker for simplified fetching and processing of RNA-seq and microarray data. Seeker is a wrapper around various existing tools, and provides a standard interface, simple parallelization, and detailed logging. Seeker’s primary output—sample metadata and gene expression values based on Entrez or Ensembl Gene IDs—can be directly plugged into a differential expression analysis. To maximize reproducibility, seeker is available as a standalone R package and in a Docker image that includes all dependencies, both of which are accessible at https://seeker.hugheylab.org.
Arsenic induced alteration of neuroregulatory gene expression in Macrobrachium lamarrei: a neurotoxicological approach to grooming behaviour
Authors: Munshi Chayan , Mukhuty Alpana , Bandyopadhyay Arindam , Bhowmik Arpan Dey , Mondal Paritosh , Shaw Pallab , Bhattacharya Shelley 
Published: September 2022

AbstractArsenic is a highly active neuromodulator which can induce neurological disorders in invertebrates. The present study is a neurotoxicological approach to assess the toxicity of arsenic trioxide, where grooming behaviour is considered as a behavioural biomarker of arsenic induced stress in the prawns. Non-lethal exposure to arsenic trioxide, manipulates the expression pattern of neuroregulatory marker genes in a freshwater prawn, Macrobrachium lamarrei and induces symptoms of autism spectrum disorders (ASDs) in a short time.
Low polyethylene glycol (PEG) concentration contributes to photoprotection in Chlamydomonas reinhardtii under highlight stress
Authors: Xavier Jerome , Yadav Ranay Mohan , Subramanyam Rajagopal 
Published: September 2022

AbstractThe highlight is one of the major problems encountered by all the autotrophs in the natural environment, as it affects the photosynthetic performance of these organisms, they were equipped themself with the diverse photoprotective mechanism. However, the drastic climate change in recent years had a more lethal effect on these organisms as it is beyond their threshold to withstand. In the past decade, scientists have unravelled many photoprotective mechanisms like qE, qZ, qT and qI (NPQ) used by autotrophs to combat highlight stress and the thirst for discovering such a new mechanism remains constant. In this regard, we studied the effect of mild osmotic stress (2%PEG) in alleviating high-light stress using Chlamydomonas (C) reinhardtii as a model system. The cells were grown in low Polyethylene glycol (PEG)-induced osmotic stress at varying light intensities; their response to these treatments had been examined via biochemical and biophysical approaches. The PEG-treated cells showed better growth and photosynthetic efficiency even at highlight than control, but their NPQ level is lesser than control, suggesting a unique or novel photoprotective mechanism is operating in PEG-treated samples. The Circular dichroism and ATG8 localization assay suggest that supercomplexes organization is not much disturbed in PEG-treated samples irrespective of light intensity. Also, the latter indicates that PEG-treated cells were healthier than the control at the highlight. This result is promising as we can improve the algal biomass under natural environmental conditions with fluctuating light intensity. As algal biomass has immense commercial importance in biofuel production, cosmetics and pharmaceutical application. This mechanism can be exploited to promote the socio-economic status of our nation.HighlightsPEG application triggers ROS accumulations, stimulating signalling cascade and overcoming highlight-induced compromise in biomass.Under highlight, the photosynthetic pigment (chlorophyll and carotenoid) constantly increased with PEG except for C-250. Specifically, the photoprotective pigment like violaxanthin and lutein has been increased.PEG shielding stabilizes pigment-protein interaction, confirming that the supercomplex organization is in its native state.PEG keeps low ATG8 accumulation, preventing cells and enabling it to combat highlights more effectively.Graphical abstract
Chlamydia trachomatis effectors target the mitochondria and alter mitochondrial protein composition
Authors: Dimond Zoe , Bauler Laura D. , Zhang Yixiang , Carmody Aaron , Hackstadt Ted 
Published: September 2022

AbstractMitochondria are critical cellular organelles that perform a wide variety of functions including energy production and immune regulation. To perform these functions, mitochondria contain approximately 1,500 proteins, the majority of which are encoded in the nuclear genome, translated in the cytoplasm, and translocated to the mitochondria using distinct mitochondria targeting sequences (MTS). Bacterial proteins can also contain MTS and localize to the mitochondria. For the obligate intracellular human pathogen, Chlamydia trachomatis, interaction with various host cell organelles promotes intracellular replication. However, the extent and mechanisms through which Chlamydia interact directly with mitochondria remain unclear. We investigated the presence of MTS in the C. trachomatis genome and discovered 30 genes with around 70% or greater probability of mitochondrial localization. Five are translocated to the mitochondria upon ectopic expression in HeLa cells. Mass spectrometry of isolated mitochondria from infected cells revealed that two of these proteins localize to the mitochondria during infection. Comparison of mitochondria from infected and uninfected cells suggests that chlamydial infection affects mitochondrial protein composition. Around 125 host proteins were significantly decreased or absent in mitochondria from infected cells. Among these are pro-apoptotic factors and those related to mitochondrial fission/fusion dynamics. Conversely, 82 host proteins were increased in or specific to mitochondria of infected cells, many of which act as anti-apoptotic factors and upregulators of cellular metabolism. These data support the notion that C. trachomatis specifically targets host mitochondria to manipulate cell fate decisions and metabolic function to support pathogen survival and replication.ImportanceObligate intracellular bacteria have evolved multiple means to promote their intracellular survival and replication within the otherwise harsh environment of the eukaryotic cell. Nutrient acquisition and avoidance of cellular defense mechanisms are critical to an intracellular lifestyle. Mitochondria are critical organelles that produce energy in the form of ATP and regulate programmed cell death responses to invasive pathogenic microbes. Cell death prior to completion of replication would be detrimental to the pathogen. C. trachomatis produces at least two and possibly more proteins that target the mitochondria. Collectively, C. trachomatis infection modulates mitochondrial protein composition favoring a profile suggestive of down-regulation of apoptosis.
A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titres
Authors: McCarthy Patrick , Pathakamuri Joseph A , Kuebler Daniel , Neves Jocelyn , Krohn Madison , Rohall Michael , Archibeque Isaac , Giese Heidi , Werner Martina , Thomann Ulrich 
Published: September 2022

AbstractThe COVID-19 pandemic has revealed a crucial need for rapid, straightforward collection and testing of biological samples. Serological antibody assays can analyse patient blood samples to confirm immune response following mRNA vaccine administration or to verify past exposure to the SARS-CoV-2 virus. While blood tests provide vital information for clinical analysis and epidemiology, sample collection is not uncomplicated. This process requires a visit to the doctor’s office, a professionally trained phlebotomist to draw several millilitres of blood, processing to yield plasma or serum, and necessitates appropriate cold chain storage to preserve the specimen. The Covaris truCOLLECT Whole Blood Collection Kit allows for a lancet-based, decentralised capillary blood collection of exactly metered low volumes and eliminates the need for refrigerated transport and storage through the process of active desiccation. Anti-SARS CoV-2 spike and nucleocapsid protein antibody titres in plasma samples collected via venepuncture were compared to antibody titres in whole blood extracts obtained by treating desiccated whole blood samples stored in truCOLLECT sampling devices with Covaris Adaptive-focused Acoustics (AFA). Pearson correlation coefficients of 0.98, 95% CI [0.96, 0.99] for anti-SARS-CoV spike protein antibodies and 0.97, 95% CI [0.94, 0.99] for anti-SARS-CoV-2 nucleocapsid protein antibodies were observed. These data suggest that serology testing using desiccated whole blood samples collected and stored in truCOLLECT devices can be a convenient and cost-effective alternative to conventionally collected plasma.
Analysis of Healthcare Seeking Behavior Among Patients Visiting Public Primary and Secondary Healthcare Facilities in an Urban Indian District
Authors: Fatma Najiya , Ramamohan Varun 
Published: September 2022

AbstractIn this work, we examined healthcare seeking behavior (HSB) of patients visiting public healthcare facilities in an urban context. We conducted a cross-sectional survey across twenty-two primary and secondary public healthcare facilities in the South-west Delhi district in India. The survey was designed to ascertain from patients at these facilities their HSB - i.e., on what basis patients decide the type of healthcare facility to visit, or which type of medical practitioner to consult. From each facility visited, we also collected operational information, such as the average number of patients visiting per day, and the medical services provided at each facility. Based on participant responses, we observed that factors such as wait time, prior experience with care providers, distance from the facility, and also socioeconomic and demographic factors such as annual income, educational qualification, and gender significantly influenced preferences of patients in choosing healthcare facilities. We used binomial and multinomial logistic regression to determine associations between HSB and socioeconomic and demographic attributes of patients at a 0.05 level of significance. Our statistical analyses revealed that patients in the lower income group preferred to seek treatment from public healthcare facilities (OR = 3.51, 95% CI = (1.65, 7.46)) irrespective of the perceived severity of their illness, while patients in the higher income group favored directly consulting specialized doctors (OR = 2.71, 95% CI = (1.34, 5.51)). Other factors such as having more than two children increased probability of seeking care from public facilities. This work contributes to the literature by providing quantitative evidence regarding overall patient HSB, especially at primary and secondary public healthcare facilities, regardless of their presenting illness, and operational information regarding healthcare delivery at these facilities. This work can inform policy designed to improve accessibility and quality of care at public primary and secondary healthcare facilities in India.
Single-strain behavior predicts responses to environmental pH and osmolality in the gut microbiota
Authors: Ng Katharine M. , Pannu Sagar , Liu Sijie , Burckhardt Juan C. , Hughes Thad , Van Treuren William , Nguyen Jen , Naqvi Kisa , Nguyen Bachviet , Clayton Charlotte A. , Pepin Deanna M. , Collins Samuel R. , Tropini Carolina 
Published: September 2022

AbstractChanges to gut environmental factors such as pH and osmolality due to disease or drugs correlate with major shifts in microbiome composition; however, we currently cannot predict which species can tolerate such changes or how the community will be affected. Here, we assessed the growth of 92 representative human gut bacterial strains spanning 28 families across multiple pH values and osmolalities in vitro. The ability to grow in extreme pH or osmolality conditions correlated with the availability of known stress response genes in many cases, but not all, indicating that novel pathways may participate in protecting against acid or osmotic stresses. Machine learning analysis uncovered genes or subsystems that are predictive of differential tolerance in either acid or osmotic stress. For osmotic stress, we corroborated the increased abundance of these genes in vivo during osmotic perturbation. The growth of specific taxa in limiting conditions in isolation in vitro correlated with survival in complex communities in vitro and in an in vivo mouse model of diet-induced intestinal acidification. Our data show that in vitro stress tolerance results are generalizable and that physical parameters may supersede interspecies interactions in determining the relative abundance of community members. Importantly, we provide an extensive resource for predicting shifts in microbial composition and gene abundance in complex perturbations. Furthermore, this work highlights the physical environment as a major driver of bacterial composition and the importance of performing physical measurements in animal and clinical studies to elucidate the drivers of shifts in microbiota abundance.Significance StatementChanges in pH and particle concentration (osmolality) commonly result from gut disease or the ingestion of common drugs, causing changes in bacterial growth and microbiota composition within the intestine. Thus far, the effects of physical parameters on the growth of intestinal bacterial taxa have not been well documented in the context of predicting microbiota community composition. To address this gap, we examined the growth of 92 bacterial species under varying pH and osmolality conditions. We found that physical parameters are key predictors of bacterial abundance in individual-strain cultures and in complex bacterial communities. Moreover, our results identified specific genes and pathways that are predictive of growth in specific environments. Together, these findings can aid in determining the effectiveness of microbiota therapies in gut environments subjected to various perturbations.
The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan
Authors: Mobley James A. , Molyvdas Adam , Kojima Kyoko , Jilling Tamas , Li Jian-Liang , Garantziotis Stavros , Matalon Sadis 
Published: September 2022

ABSTRACTThe COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.