bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chaperonin-mediated Winter Cold Response via Circadian Clock Components inArabidopsis
Authors: Jeong Goowon , Jeon Myeongjune , Kyung Jinseul , Jeong Daesong , Shin Jinwoo , Shin Yourae , Hwang Daehee , Hyun Youbong , Lee Ilha 
Published: May 2024

AbstractVernalization and cold acclimation are plant strategies that evolved to enhance their fitness during the winter season. The molecular mechanisms behind these processes in Arabidopsis have been intensively studied. However, how plants measure the duration of long-term cold exposure has not been fully understood. Our research shows that cytosolic chaperonin is crucial for appropriate long-term cold responses by regulating plant circadian clocks. Furthermore, one of the clock components, REVEILLE4 (RVE4) and RVE8 directly activateVERNALIZATION INSENSITIVE 3(VIN3) and theC-REPEAT BINDING FACTOR(CBF)/DEHYDRATION-RESPONSIVE ELEMENT BINDING 1(DREB1) family genes, which are key regulators of vernalization and cold acclimation, respectively. The activation of theVIN3andCBF/DREB1genes was specific to the time of day, indicating that cold exposure during the day is critical for long-term cold responses. Our research delves deeper into understanding the regulatory mechanism governing these two distinct long-term cold responses.
Wolbachiastrengthens the match between pre-mating and early post-mating isolation in spider mites
Authors: Cruz Miguel A. , Magalhães Sara , Bakırdöven Murat , Zélé Flore 
Published: May 2024

AbstractEndosymbiotic reproductive manipulators are widely studied as sources of post-zygotic isolation in arthropods, but their effect on pre-zygotic isolation between genetically differentiated populations has garnered less attention. We tested this using two partially isolated populations of the red and green colour forms ofTetranychus urticae, either uninfected or infected with differentWolbachiastrains, one inducing cytoplasmic incompatibility and the other not. We first investigated male and female preferences, and found that, in absence of infection, females were not choosy but all males preferred red-form females.Wolbachiaeffects were more subtle, with only the CI-inducing strain slightly strengthening colour-form based preferences. We then performed a double-mating experiment to test how incompatible matings affect subsequent mating behaviour and offspring production, as compared to compatible matings. Females mated with an incompatible male (infected and/or heterotypic) were more attractive and/or receptive to subsequent (compatible) matings, although analyses of offspring production revealed no clear benefit for this re-mating behaviour (i.e., apparently unaltered first male sperm precedence). Finally, by computing the relative contributions of each reproductive barrier to total isolation, we showed that pre-mating isolation matches both host-associated andWolbachia-induced post-mating isolation, suggesting thatWolbachiacould contribute to reproductive isolation in this system.
Proline substitutions in the ASIC1 β11-12 linker slow desensitization
Authors: Purohit Rutambhara , Couch Tyler , MacLean David M. 
Published: May 2024

AbstractDesensitization is a prominent feature of nearly all ligand gated ion channels. Acid-sensing ion channels (ASIC) undergo desensitization within hundreds of milliseconds to seconds upon continual extracellular acidification. The ASIC mechanism of desensitization is primarily due to the isomerization or “flipping” of a short linker joining the 11thand 12thbeta sheets in the extracellular domain. In the resting and active states this β11-12 linker adopts an “upward” conformation while in the desensitized conformation the linker assumes a “downward” state. To accommodate this “downward” state, specific peptide bonds within the linker adopt either trans-like or cis-like conformations. Since proline-containing peptide bonds undergo cis-trans isomerization very slowly, we hypothesized that introducing proline residues in the linker may slow or even abolish ASIC desensitization, potentially providing a valuable research tools. Proline substitutions in the chicken ASIC1 β11-12 linker (L414P and Y416P) slowed desensitization decays approximately 100 to 1000-fold as measured in excised patches. Both L414P and Y416P shifted the steady state desensitization curves to more acidic pHs while activation curves and ion selectivity of these slow-desensitizing currents were largely unaffected. To investigate the functional stoichiometry of desensitization in the trimeric ASIC, we created families of L414P and Y416P concatemers with zero, one, two or three proline substitutions in all possible configurations. Introducing one or two L414P or Y416P mutations only slightly attenuated desensitization, suggesting that conformational changes in the remaining faster wild type subunits were sufficient to desensitize the channel. These data highlight the unusual cis-trans isomerization mechanism of ASIC desensitization and support a model where a single subunit is sufficient to desensitize the entire channel.
Clonal sharing of CD8+ T-cells links skin and joint inflammation in psoriatic arthritis
Authors: Durham Lucy E. , Humby Frances , Ng Nora , Gray Elizabeth H. , Ryan Sarah E. , Ross Rosie , Povoleri Giovanni A. M. , Nuamah Rosamond , Fung Kathy , Kallayil Athul Menon , Dhami Pawan , Kirkham Bruce W. , Taams Leonie S. 
Published: May 2024

AbstractWe hypothesised that skin and joint inflammation in psoriatic arthritis (PsA) is linked in terms of CD8+ T-cell phenotype and clonality. We employed scRNAseq to directly compare the transcriptional signature and T-cell receptor repertoire of memory T-cells from paired skin and synovial tissue and/or fluid from patients with PsA. We identified an enrichment of type-17 CD8+ tissue-resident memory (TRM) T-cells in both skin and joint, with a stronger IL-17 signature in the skin than the joint. Several T-cell clones were shared between the skin and joint and these shared clones tended to have the same signature at both sites, characterised by increased expression of genes associated with a cytotoxic, tissue-resident phenotype. Our findings support the hypothesis that skin and joint inflammation in PsA is linked in terms of T-cell clonality and raises the possibility that specific T-cells migrate between these compartments to propagate inflammation across both sites.
Metagenomic coverage bias at transcription start sites is correlated with gene expression
Authors: Qian Gordon , Coleman Izaak , Korem Tal , Ho Joshua W. K. 
Published: May 2024

AbstractMetagenomic sequencing is presumed to provide unbiased sampling of all the genetic material in a sample. Downstream analysis methods, such as binning, gene copy number analysis, structural variations, or single nucleotide polymorphism analysis, commonly assume an even distribution across the genome after accounting for known artefacts such as GC content. We discovered coverage bias across gut microbiome species, manifesting as a difference in coverage before and after bacterial transcription start sites. Using matched metatranscriptomic and metagenomic sequencing data, we demonstrate that this bias correlates with gene expression. Potential artefacts such as the sequencing technology, reference genome used for alignment, and mappability bias were investigated across multiple datasets and shown to not be factors for association. While GC bias was found correlated with coverage bias, the association of coverage bias with gene expression remains significant after adjusting for GC bias. Paired-end read mapping demonstrated an enrichment in 5’ read ends immediately downstream of the TSS which was partly a byproduct of unmapped reads upstream of the TSS. Our observations suggest the existence of strain-level variation where sequence variation in the promoter site region is preventing proper read alignment to the reference genome. The correlation of this phenomenon with gene expression may also reflect evolutionary footprints for fine-tuning the regulation of gene expression. Understanding the source of this sequence variation and the biological implications of this artefact will be useful not only to better characterise microbial functions but also to improve interpretations of strain level dynamics.ImportanceSequencing coverage calculated from metagenomic sequencing data is extensively used in the microbiome field, providing valuable information about microbial abundances, gene (functional) abundances, growth rates, and genomic variations. Understanding factors that impact the distribution of coverage along genomes is therefore important for multiple applications. In this study, we report on uneven read coverage across the transcription start sites of bacterial genomes that is correlated with gene expression levels. We determine that this bias is independent of multiple factors including GC bias, and arises due to higher strain divergence from reference genomes upstream of the transcript start site. We propose that evolutionary finetuning of gene expression in competitive microbial ecosystems can drive genetic mutations at the promoter site. Our findings suggest the potential to glean gene regulatory information from metagenomic data, and better understand how ecological factors shape genomes in the microbiome and their sequencing coverage.
Exportin-1 functions as an adaptor for transcription factor-mediated docking of chromatin at the nuclear pore complex
Authors: Ge Tiffany , Brickner Donna Garvey , Zehr Kara , VanBelzen D. Jake , Zhang Wenzhu , Caffalette Christopher , Ungerleider Sara , Marcou Nikita , Chait Brian , Rout Michael P. , Brickner Jason H. 
Published: May 2024

AbstractNuclear pore proteins (Nups) in yeast, flies and mammals physically interact with hundreds or thousands of chromosomal sites, which impacts transcriptional regulation. In budding yeast, transcription factors mediate interaction of Nups with enhancers of highly active genes. To define the molecular basis of this mechanism, we exploited a separation-of-function mutation in the Gcn4 transcription factor that blocks its interaction with the nuclear pore complex (NPC) without altering its DNA binding or activation domains. SILAC mass spectrometry revealed that this mutation reduces the interaction of Gcn4 with the highly conserved nuclear export factor Crm1/Xpo1. Crm1 both interacts with the same sites as Nups genome-wide and is required for Nup2 to interact with the yeast genome.In vivo, Crm1 undergoes extensive and stable interactions with the NPC.In vitro, Crm1 binds to Gcn4 and these proteins form a complex with the nuclear pore protein Nup2. Importantly, the interaction between Crm1 and Gcn4 does not require Ran-GTP, suggesting that it is not through the nuclear export sequence binding site. Finally, Crm1 stimulates DNA binding by Gcn4, supporting a model in which allosteric coupling between Crm1 binding and DNA binding permits docking of transcription factor-bound enhancers at the NPC.
T-ChIC: multi-omic detection of histone modifications and full-length transcriptomes in the same single cell
Authors: Zeller Peter , Blotenburg Marloes , Bhardwaj Vivek , de Barbanson Buys Anton , Salmén Fredrik , van Oudenaarden Alexander 
Published: May 2024

AbstractEpigenetic mechanisms, such as histone modifications, are key regulators of transcription and maintenance of cell identity. While our knowledge concerning cell type-specific histone modifications has constantly increased, we still know little about the interplay between epigenetics and transcription at the level of the individual cell. To gain an understanding of this process, we developed T-ChIC (Transcriptome + Chromatin ImmunoCleavage), a method allowing for the detection of full-length transcripts and histone modifications in the same single cell. We applied this technique to anin vitromodel of gastrulation and monitored the coordinated dynamics of the transcriptome and active and repressive histone modifications as mouse embryonic stem cells differentiate into the three germ layers. Our analysis reveals a germ layer-dependent coupling between chromatin regulation and transcriptional states.
Evaluation of Hi-C sequencing for the detection of gene fusions in hematologic and solid pediatric cancer samples
Authors: Schmitt Anthony D. , Sikkink Kristin , Ahmed Atif A. , Melnyk Shadi , Reid Derek , Van Meter Logan , Guest Erin M. , Lansdon Lisa A. , Pastinen Tomi , Pushel Irina , Yoo Byunggil , Farooqi Midhat S. 
Published: May 2024

AbstractHiC sequencing is a DNA-based next-generation sequencing method that preserves the 3D conformation of the genome and has shown promise in detecting genomic rearrangements in translational research studies. To evaluate HiC as a potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia and sarcoma specimens previously positive for clinically significant genomic rearrangements. Archived specimen types tested included viable and nonviable frozen leukemic cells, as well as formalin-fixed paraffin-embedded (FFPE) tumor tissues. Initially, pediatric acute myeloid leukemia (AML) and alveolar rhabdomyosarcoma (A-RMS) specimens with known genomic rearrangements were subjected to HiC analysis to assess analytical concordance. Subsequently, a discovery cohort consisting of AML and acute lymphoblastic leukemia (ALL) cases with no known genomic rearrangements based on prior clinical diagnostic testing were evaluated to determine whether HiC could detect rearrangements. Using a standard sequencing depth of 50 million raw read-pairs per sample, or approximately 5X raw genomic coverage, 100% concordance was observed between HiC and previous clinical cytogenetic and molecular testing. In the discovery cohort, a clinically relevant gene fusion was detected in 45% of leukemia cases (5/11). This study demonstrates the value of HiC sequencing to medical diagnostic testing as it identified several clinically significant rearrangements, including those that might have been missed by current clinical testing workflows.Key pointsHiC sequencing is a DNA-based next-generation sequencing method that preserves the 3D conformation of the genome, facilitating detection of genomic rearrangements.HiC was 100% concordant with clinical diagnostic testing workflows for detecting clinically significant genomic rearrangements in pediatric leukemia and rhabdomyosarcoma specimens.HiC detected clinically significant genomic rearrangements not previously detected by prior clinical cytogenetic and molecular testing.HiC performed well with archived non-viable and viable frozen leukemic cell samples, as well as archived formalin-fixed paraffin-embedded tumor tissue specimens.
A new form of hereditary iron overload unlinked to known hereditary haemochromatosis genes
Authors: Wallace Daniel F. , Subramaniam V. Nathan 
Published: May 2024

AbstractHereditary iron overload conditions are normally caused by mutations in theHFEgene or other genes involved in the regulation of iron homeostasis. We describe a family with an iron overload condition with apparent autosomal dominant inheritance and phenotypic similarities to the classical form of ferroportin disease. The condition is characterised by elevated serum ferritin levels with normal or mildly elevated transferrin saturation and prominent iron deposition in both Kupffer cells and hepatocytes. Serum hepcidin levels were elevated in affected members of the pedigree and correlated with serum ferritin concentration. No pathogenic variants were identified inHFEorSLC40A1, the gene encoding ferroportin. Whole genome linkage analysis showed maximal linkage of the iron overload phenotype to regions on chromosomes 1, 3, 12, 18 and 19, indicating that affected members of this family do not have a variant form of ferroportin disease and are likely to have a new form of hereditary iron overload due to defects in another gene.
CLINICOPATHOLOGIC FEATURES OF URINARY BLADDER CANCER AT A TERTIARY HOSPITAL IN WESTERN KENYA
Authors: Oduor Charles Sore , Mugalo Edward , Kirongo Geoffrey 
Published: May 2024

AbstractBackgroundUrinary bladder cancer is the ninth leading cause of morbidity and mortality globally, with a prevalence of 3% of all cancer diagnoses. Its local prevalence in Kenya is 1.89 per 100, 000 persons with previously documented studies describing it as a disease of the elderly. Local anecdotal data indicate that younger patients have begun presenting with bladder cancer.ObjectivesTo establish the clinicopathological features of urinary bladder cancer.MethodsA prospective descriptive hospital-based study among participants with bladder cancer at MTRH Urology department, sampled using a census sampling technique. Socio-demographic and clinical characteristics as well as predisposing factors were obtained through both interviews and a review of medical records. Disease staging was based on radiological imaging findings and histopathology reports. Statistical tests of association between socio-demographic characteristics, predisposing factors as well as the histological type, and Tumor, Node, Metastasis (TNM) stage of urinary bladder cancer were conducted using Pearson chi-square test with a critical value of ≤0.05.ResultsForty-five (45) adults aged between 21 to 85 years with a mean age of 61.84 (±14.46) years and diagnosed with urinary bladder cancer were enrolled. Majority were male (68.9%; n=31) commonly presenting with painless hematuria, exposure to agrochemicals (60%; n=27), history of cigarette smoking (31.1%; n=14) with an average pack year of 9.43 (±6.198). The most common (71.1%; n=32) clinical stage was T1while 6.7% (n=3) had metastatic disease. More than half (55.6%) had stage I according to the TNM system while 91.1% had low-grade tumors. Transitional cell carcinoma (51.1%) was the most common histological type, followed by adenocarcinoma (29%), and squamous cell carcinoma (20%).ConclusionsPatients diagnosed with bladder cancer in this study were mainly males with a mean age of 61.8 years. Majority of the participants had a history of smoking cigarettes or exposure to agrochemicals, and all presented with painless hematuria. Most patients had low-grade tumors diagnosed early.
Virome Sequencing Identifies H5N1 Avian Influenza in Wastewater from Nine Cities
Authors: Tisza Michael J. , Hanson Blake M. , Clark Justin R. , Wang Li , Payne Katelyn , Ross Matthew C. , Mena Kristina D. , Gitter Anna , Javornik-Cregeen Sara J. , Cormier Juwan , Avadhanula Vasanthi , Terwilliger Austen , Balliew John , Wu Fuqing , Rios Janelle , Deegan Jennifer , Piedra Pedro A. , Petrosino Joseph F. , Boerwinkle Eric , Maresso Anthony W. 
Published: May 2024

AbstractAvian influenza (serotype H5N1) is a highly pathogenic virus that emerged in domestic waterfowl in 1996. Over the past decade, zoonotic transmission to mammals, including humans, has been reported. Although human to human transmission is rare, infection has been fatal in nearly half of patients who have contracted the virus in past outbreaks. The increasing presence of the virus in domesticated animals raises substantial concerns that viral adaptation to immunologically naïve humans may result in the next flu pandemic. Wastewater-based epidemiology (WBE) to track viruses was historically used to track polio and has recently been implemented for SARS-CoV2 monitoring during the COVID-19 pandemic. Here, using an agnostic, hybrid-capture sequencing approach, we report the detection of H5N1 in wastewater in nine Texas cities, with a total catchment area population in the millions, over a two-month period from March 4thto April 25th, 2024. Sequencing reads uniquely aligning to H5N1 covered all eight genome segments, with best alignments to clade 2.3.4.4b. Notably, 19 of 23 monitored sites had at least one detection event, and the H5N1 serotype became dominant over seasonal influenza over time. A variant analysis suggests avian or bovine origin but other potential sources, especially humans, could not be excluded. We report the value of wastewater sequencing to track avian influenza.
A cross sectional study on “Behavioral risk factors of cardiovascular disease among adolescents of secondary level school in a sub-metropolitan city of Nepal”
Authors: Bista Sita , Puri Bishow , Maharjan Sanju , Bhandari Buna 
Published: May 2024

ABSTRACTBackgroundCardiovascular diseases (CVDs) are the leading cause of death and disability globally, where one-third of adolescents are affected. There is plenty of evidence that behavioral factors like physical inactivity, unhealthy diet, smoking, and alcohol use are major risks associated with CVDs among adolescents/school-going children.Objective(s)The main aim of this study was to assess the prevalence of behavioral risk factors of cardiovascular disease among adolescents of secondary-level schools in Tulsipur Sub Metropolitan City, Nepal.MethodsIt was a school-based cross-sectional study among 361 adolescents of grades 11 and 12 between the ages of 16 and 19. The school was selected by using a stratified proportionate sampling method. Data were collected through a self-administered structured and validated questionnaire containing socio-demographic characteristics, behavioral risk factors of CVDs and respective parent’s information. Data were analyzed using both descriptive and analytical statistics.ResultsThe most prevalent behavioral risk factor was consumption of calorie drinks (99%); followed by sedentary behavior (60%), insufficient fruit and vegetable intake (57%), physical inactivity (35%), intake of processed food high in salt (33%), refined vegetable oil use in meal preparation (19%) and added salt intake (15.5%). Similarly, the prevalence of current smoking tobacco, alcohol use and smokeless tobacco use was 12%, 10% and 9%, respectively. Mother education, ethnicity, education system were associated factors of majority of behavioral risk factors of CVDs among adolescents. Mother education, parent’s smoking habit and parent’s smokeless tobacco use were associated factors of current tobacco smoking. Parent’s smokeless tobacco use and parent’s alcohol use were associated factors of current alcohol use.ConclusionsThis study provided evidence of high prevalence of CVD risk factors among adolescents in Nepal. It demands an urgent need to effectively design appropriate interventions in household and school settings to address the risk factors at the municipal level of Nepal.