Enrichment of innate lymphoid cell populations in gingival tissue

Innate lymphoid cells (ILCs) are a population of lymphocytes that act as the first line of immunologic defense at mucosal surfaces. The ILC family in the skin, lungs, and gastrointestinal tissues has been investigated, and there are reports of individual subsets of ILCs in the oral tissues. We sought to investigate the whole ILC population (group 1, 2, and 3 subsets) in the murine gingivae and the lymph nodes draining the oral cavity. We show that ILCs made up a greater proportion of the whole CD45+ lymphocyte population in the murine gingivae (0.356% ± 0.039%) as compared with the proportion of ILCs in the draining lymph nodes (0.158% ± 0.005%). Cytokine profiling of the ILC populations demonstrated different proportions of ILC subsets in the murine gingivae versus the regional lymph nodes. The majority of ILCs in the draining lymph nodes expressed IL-5, whereas there were equal proportions of IFN-γ- and IL-5 expressing ILCs in the oral mucosa. The percentage of IL-17+ ILCs was comparable between the murine gingivae and the oral draining lymph nodes. These data suggest an enrichment of ILCs in the murine gingivae, and these ILCs reflect a cytokine profile discrepant to that of the local draining lymph nodes. These studies indicate diversity and enrichment of ILCs at the oral mucosal surface. The function of ILCs in the oral cavity remains to be determined; here, we provide a premise of ILC populations that merits future consideration in investigations of mouse models and human tissues

Community Outreach through Genomics Education Partnership

The J Craig Venter Institute (JCVI) has recently partnered with undergraduate university faculty to expand the scope of education and outreach program as part of the NIAID’s BRC initiative, by joining forces with faculty members participating in the Genomics Education Partnership (GEP). The goal of the GEP is to provide opportunities for undergraduate students to participate in genomics research and gain hands on experience. Faculty members trained on annotation methodologies and tools during the Prokaryotic Annotation Workshop conducted at JCVI, impart their knowledge in the classroom as part of the semester course. As a pilot project, we are currently collaborating with 3 groups lead by a faculty member, spread across 3 universities in the community curation of bacterial genomes. Each participating undergraduate group collectively annotates a specific bacterial genome that was sequenced at JCVI and run through the automatic annotation pipeline. Remote access to genome sequence data, pre-computed gene predictions, search results, automatic annotation and bioinformatics analysis is provided through our web-based manual annotation tool, MANATEE. The students log into JCVI genome databases with user specific ids and password and learn to annotate single genes, entire metabolic pathways leading to analysis of a question that may be unique to the genome being analyzed. Users of the genome data receive dedicated support and guidance from our in house annotation experts on the usage of JCVI’s tools and annotation methodologies. Through this exercise, the undergraduate students are introduced to concepts of genomics and bioinformatics and gain deeper understanding of the concepts of cellular metabolism and disease pathology, which may lead them to making scientific research their career path. Some groups are focusing on genome specific pathways and plan to conduct wet lab experiments to understand unique genome features. We are highly encouraged that this model of web based, remote access, community annotation has been successful and propose to leverage the community of annotators to update annotations of pathogen genomes in Pathema-BRC

Chromatin structure and evolution in the human genome

<p>Abstract</p> <p>Background</p> <p>Evolutionary rates are not constant across the human genome but genes in close proximity have been shown to experience similar levels of divergence and selection. The higher-order organisation of chromosomes has often been invoked to explain such phenomena but previously there has been insufficient data on chromosome structure to investigate this rigorously. Using the results of a recent genome-wide analysis of open and closed human chromatin structures we have investigated the global association between divergence, selection and chromatin structure for the first time.</p> <p>Results</p> <p>In this study we have shown that, paradoxically, synonymous site divergence (dS) at non-CpG sites is highest in regions of open chromatin, primarily as a result of an increased number of transitions, while the rates of other traditional measures of mutation (intergenic, intronic and ancient repeat divergence as well as SNP density) are highest in closed regions of the genome. Analysis of human-chimpanzee divergence across intron-exon boundaries indicates that although genes in relatively open chromatin generally display little selection at their synonymous sites, those in closed regions show markedly lower divergence at their fourfold degenerate sites than in neighbouring introns and intergenic regions. Exclusion of known Exonic Splice Enhancer hexamers has little affect on the divergence observed at fourfold degenerate sites across chromatin categories; however, we show that closed chromatin is enriched with certain classes of ncRNA genes whose RNA secondary structure may be particularly important.</p> <p>Conclusion</p> <p>We conclude that, overall, non-CpG mutation rates are lowest in open regions of the genome and that regions of the genome with a closed chromatin structure have the highest background mutation rate. This might reflect lower rates of DNA damage or enhanced DNA repair processes in regions of open chromatin. Our results also indicate that dS is a poor measure of mutation rates, particularly when used in closed regions of the genome, as genes in closed regions generally display relatively strong levels of selection at their synonymous sites.</p

Dissociation and its biological and clinical associations in functional neurological disorder: : systematic review and meta-analysis

BackgroundStudies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking.AimsTo systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations.MethodWe searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle–Ottawa criteria. The findings weresynthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263).ResultsSeventy-five studies were eligible (FND n = 3940; control n = 3073), most commonly prospective case–control studies (k = 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy (g = 0.90, 95% CI 0.66–1.14, I2 = 70%) and neurologicalcontrols (g = 0.56, 95% CI 0.19–0.92, I2 = 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls (g = 0.94, 95% CI 0.65–1.22, I2 = 42%) and FND samples with motor symptoms (g = 0.40, 95% CI −0.18 to 1.00, I2 = 54%). Somatoform dissociation was elevated in FND versus healthy controls (g = 1.80, 95% CI 1.25–2.34,I2 = 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations.ConclusionsOur findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed

Sources and correlates of sodium consumption in the first 2 years of life

High sodium intake during infancy and early childhood can change salt preference and blood pressure trajectories across life, representing a modifiable cardiovascular risk factor. Describing young children\u27s sodium intake is important for informing effective targets for sodium reduction

Beta cell death by cell-free DNA and outcome after clinical islet transplantation

Background: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss, and was recently validated in new-onset type 1 diabetes and in islet transplant patients. Methods: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes. Results: A distinctive peak of cfDNA was observed 1hr after transplantation in 31/37 (83.8%) of subjects. The presence and magnitude of this signal did not correlate with transplant outcome. The 1hr signal represents dead beta cells carried over into the recipient after islet isolation and culture, combined with acute cell death post infusion. Beta cell cfDNA was also detected 24hrs post-transplant (8/37 subjects, 21.6%). This signal was associated with higher 1-month insulin requirements (p=0.04), lower 1-month stimulated C-peptide levels (p=0.01) and overall worse 3-month engraftment, by insulin independence (ROC:AUC=0.70, p=0.03) and Beta 2 score (ROC:AUC=0.77, p=0.006). Conclusions: cfDNA-based estimation of beta cell death 24hrs after islet allotransplantation correlates with clinical outcome and could predict early engraftment.B.G.-L. is supported through the Alberta Innovates :Health Solutions (AIHS) Clinician Fellowship and through the CNTRP. A.P. is supported through AIHS Postgraduate Fellowship and CNTRP. A.M.J.S. is supported through AIHS, and holds a Canada Research Chair in Transplantation Surgery and Regenerative Medicine funded through the Government of Canada. A.M.J.S. is also funded by AIHS Collaborative Research and Innovation Opportunity Team Award and the Diabetes Research Institute Foundation of Canada (DRIFCan). Supported by grants from the Juvenile Diabetes Research Foundation (JDRF) (3-SRA-2014-38-Q-R, to Y.D. and A.M.J.S.), National Institute of Health (NIH) (HIRN grant UC4 DK104216, to Y.D.), DON foundation (Stichting Diabetes Onderzoek Nederland) (to Y.D), the European Union (ELASTISLET project, to Y.D.) and the Kahn foundation (to Y.D., R.S., and B.G.). Supported in part by a grant from The United States Agency for International Development (USAID) American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University sequencing core facilit

Evaluation of Three Automated Genome Annotations for Halorhabdus utahensis

Genome annotations are accumulating rapidly and depend heavily on automated annotation systems. Many genome centers offer annotation systems but no one has compared their output in a systematic way to determine accuracy and inherent errors. Errors in the annotations are routinely deposited in databases such as NCBI and used to validate subsequent annotation errors. We submitted the genome sequence of halophilic archaeon Halorhabdus utahensis to be analyzed by three genome annotation services. We have examined the output from each service in a variety of ways in order to compare the methodology and effectiveness of the annotations, as well as to explore the genes, pathways, and physiology of the previously unannotated genome. The annotation services differ considerably in gene calls, features, and ease of use. We had to manually identify the origin of replication and the species-specific consensus ribosome-binding site. Additionally, we conducted laboratory experiments to test H. utahensis growth and enzyme activity. Current annotation practices need to improve in order to more accurately reflect a genome's biological potential. We make specific recommendations that could improve the quality of microbial annotation projects

Primary health care services for the aged in the United Arab Emirates: a comparison of two models of care

Aim: To compare the quality of aged care provided by two different models of primary health care services in the United Arab Emirates. Methods: Cross sectional survey by chart review of 200 consecutive people aged 65 years and over attending two primary health care centers located in adjacent suburbs and serving populations with similar characteristics; a resource intensive center (RIC) and the other a resource thrifty center (RTC). Quality indicators were blood pressure levels in hypertensives and glycosylated hemoglobin (HbA1c) levels in diabetics. Results: There was no variation in age, sex or number of visits per year between the clinics. Osteoarthritis, hypertension, and diabetes were the most common diagnoses at both. The people attending the RIC had a substantially higher level of comorbidity (RIC=1.19±1.18, RTC=0.63 ± 0.68, p < 0.001), the average systolic and diastolic blood pressure for those diagnosed with hypertension was in the normal range at the RIC (138.5 ± 19.8/77.1 ± 9.9), whereas it was significantly higher and in the elevated range at the RTC (149.5 ± 17.7/85.2 ± 9.1, p < 0.001) and the HbA1c was significantly lower at the RIC (7.7 ± 1.4) than at the RTC (9.5 ± 2.0, p < 0.001). Conclusions:The quality of health outcomes for the two chronic diseases, hypertension and diabetes, appeared significantly higher at the RIC, when compared with the RTC. However, there may have been significant selection bias. Further studies are needed to determine if the RIC improves quality measures in other aspects of chronic disease care and provides a more cost effective health care service

Characterisation of Genome-Wide Association Epistasis Signals for Serum Uric Acid in Human Population Isolates

Genome-wide association (GWA) studies have identified a number of loci underlying variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the largest effect identified so far. Gene-gene interactions (epistasis) are largely unexplored in these GWA studies. We performed a full pair-wise genome scan in the Italian MICROS population (n = 1201) to characterise epistasis signals in SUA levels. In the resultant epistasis profile, no SNP pairs reached the Bonferroni adjusted threshold for the pair-wise genome-wide significance. However, SLC2A9 was found interacting with multiple loci across the genome, with NFIA - SLC2A9 and SLC2A9 - ESRRAP2 being significant based on a threshold derived for interactions between GWA significant SNPs and the genome and jointly explaining 8.0% of the phenotypic variance in SUA levels (3.4% by interaction components). Epistasis signal replication in a CROATIAN population (n = 1772) was limited at the SNP level but improved dramatically at the gene ontology level. In addition, gene ontology terms enriched by the epistasis signals in each population support links between SUA levels and neurological disorders. We conclude that GWA epistasis analysis is useful despite relatively low power in small isolated populations