Soluble CD52 mediates immune suppression by human seminal fluid.

Seminal fluid provides for the carriage and nutrition of sperm, but also modulates immunity to prevent allo-rejection of sperm by the female. Immune suppression by seminal fluid has been associated with extracellular vesicles, originally termed prostasomes, which contain CD52, a glycosylated glycophosphoinositol-anchored peptide released from testicular epithelial cells. Previously, we reported that human T cell-derived CD52, bound to the danger-associated molecular pattern protein, high mobility group box 1 (HMGB1), suppresses T cell function via the inhibitory sialic acid-binding immunoglobulin-like lectin-10 (Siglec-10) receptor.

Dietary patterns during pregnancy and maternal and birth outcomes in women with type 1 diabetes: the Environmental Determinants of Islet Autoimmunity (ENDIA) study.

Aims/hypothesis: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes.

Community use of oral antibiotics transiently reprofiles the intestinal microbiome in young Bangladeshi children.

Antibiotics may alter the gut microbiome, and this is one of the mechanisms by which antimicrobial resistance may be promoted. Suboptimal antimicrobial stewardship in Asia has been linked to antimicrobial resistance. We aim to examine the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in 1093 Bangladeshi infants.

Environmental Determinants of Islet Autoimmunity (ENDIA) longitudinal prospective pregnancy to childhood cohort study of Australian children at risk of type 1 diabetes: parental demographics and birth information.

Introduction: The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort's parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes.

Research Design And Methods: Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D.

Feasibility and Validity of In-Home Self-Collected Capillary Blood Spot Screening for Type 1 Diabetes Risk.

Self-collection of a blood sample for autoantibody testing has potential to facilitate screening for type 1 diabetes risk. We sought to determine the feasibility and acceptability of this approach and the performance of downstream antibody assays. People living with type 1 diabetes and their family members ( = 97) provided paired capillary blood spot and serum samples collected, respectively, by themselves and a health worker.

Human HLA-DR+CD27+ regulatory T cells show enhanced antigen-specific suppressive function.

Regulatory T cells (Tregs) have potential for the treatment of autoimmune diseases and graft rejection. Antigen specificity and functional stability are considered critical for their therapeutic efficacy. In this study, expansion of human Tregs in the presence of porcine PBMCs (xenoantigen-expanded Tregs, Xn-Treg) allowed the selection of a distinct Treg subset, coexpressing the activation/memory surface markers HLA-DR and CD27 with enhanced proportion of FOXP3+Helios+ Tregs.

Artificial intelligence takes center stage: exploring the capabilities and implications of ChatGPT and other AI-assisted technologies in scientific research and education.

The emergence of large language models (LLMs) and assisted artificial intelligence (AI) technologies have revolutionized the way in which we interact with technology. A recent symposium at the Walter and Eliza Hall Institute explored the current practical applications of LLMs in medical research and canvassed the emerging ethical, legal and social implications for the use of AI-assisted technologies in the sciences. This paper provides an overview of the symposium's key themes and discussions delivered by diverse speakers, including early career researchers, group leaders, educators and policy-makers highlighting the opportunities and challenges that lie ahead for scientific researchers and educators as we continue to explore the potential of this cutting-edge and emerging technology.

A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.

Aims/introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically at-risk for type 1 diabetes followed from birth who had developed islet autoantibodies ("seroconverted"), by measuring mucosa-associated cytokines in their sera.

Gut microbiota maturity mediates the protective effect of siblings on food allergy.

Background: The mechanisms underlying the protective effect of older siblings on allergic disease remain unclear but may relate to the infant gut microbiota.

Objective: We sought to investigate whether having older siblings decreases the risk of IgE-mediated food allergy by accelerating the maturation of the infant gut microbiota.

Methods: In a birth cohort assembled using an unselected antenatal sampling frame (n = 1074), fecal samples were collected at 1 month, 6 months, and 1 year, and food allergy status at 1 year was determined by skin prick test and in-hospital food challenge.

Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort.

The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals.

Maternal gut microbiota during pregnancy and the composition of immune cells in infancy.

Background: Preclinical studies have shown that maternal gut microbiota during pregnancy play a key role in prenatal immune development but the relevance of these findings to humans is unknown. The aim of this prebirth cohort study was to investigate the association between the maternal gut microbiota in pregnancy and the composition of the infant's cord and peripheral blood immune cells over the first year of life.

Methods: The Barwon Infant Study cohort (=1074 infants) was recruited using an unselected sampling frame.

Decreased occurrence of ketoacidosis and preservation of beta cell function in relatives screened and monitored for type 1 diabetes in Australia and New Zealand.

Aims: Islet autoantibody screening of infants and young children in the Northern Hemisphere, together with semi-annual metabolic monitoring, is associated with a lower risk of ketoacidosis (DKA) and improved glucose control after diagnosis of clinical (stage 3) type 1 diabetes (T1D). We aimed to determine if similar benefits applied to older Australians and New Zealanders monitored less rigorously.

Methods: DKA occurrence and metabolic control were compared between T1D relatives screened and monitored for T1D and unscreened individuals diagnosed in the general population, ascertained from the Australasian Diabetes Data Network.

Household size, T regulatory cell development, and early allergic disease: a birth cohort study.

Background: Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally.

Objective: We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age.

Functional Analysis of Mmd2 and Related PAQR Genes During Sex Determination in Mice.

Introduction: Sex determination in eutherian mammals is controlled by the Y-linked gene Sry, which drives the formation of testes in male embryos. Despite extensive study, the genetic steps linking Sry action and male sex determination remain largely unknown. Here, we focused on Mmd2, a gene that encodes a member of the progestin and adipoQ receptor (PAQR) family.

A Long-Term Evaluation of Facebook for Recruitment and Retention in the ENDIA Type 1 Diabetes Pregnancy-Birth Cohort Study.

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) study is an Australia-wide pregnancy-birth cohort study following children who have a first-degree relative with type 1 diabetes (ACTRN1261300794707). A dedicated ENDIA Facebook page was established in 2013 with the aim of enhancing recruitment and supporting participant retention through dissemination of study information. To measure the impact of Facebook, we evaluated the sources of referral to the study, cohort demographics, and withdrawal rates.

Mental Health During Late Pregnancy and Postpartum in Mothers With and Without Type 1 Diabetes: The ENDIA Study.

Objective: Pregnancy and type 1 diabetes are each associated with increased anxiety and depression, but the combined impact on well-being is unresolved. We compared the mental health of women with and without type 1 diabetes during pregnancy and postpartum and examined the relationship between mental health and glycemic control.

Research Design And Methods: Participants were women enrolled from 2016 to 2020 in the Environmental Determinants of Islet Autoimmunity (ENDIA) study, a pregnancy to birth prospective cohort following children with a first-degree relative with type 1 diabetes.

Women with type 1 diabetes exhibit a progressive increase in gut Saccharomyces cerevisiae in pregnancy associated with evidence of gut inflammation.

Aims: Studies of the gut microbiome have focused on its bacterial composition. We aimed to characterize the gut fungal microbiome (mycobiome) across pregnancy in women with and without type 1 diabetes.

Methods: Faecal samples (n = 162) were collected from 70 pregnant women (45 with and 25 without type 1 diabetes) across all trimesters.

Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation.

Background: Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here, we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D.

Cytotoxicity-Related Gene Expression and Chromatin Accessibility Define a Subset of CD4+ T Cells That Mark Progression to Type 1 Diabetes.

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of children at risk associated with progression to islet autoimmunity.

Differential requirement for the Polycomb repressor complex 2 in dendritic cell and tissue-resident myeloid cell homeostasis.

Dendritic cells (DCs) and macrophages are at the forefront of immune responses, modifying their transcriptional programs in response to their tissue environment or immunological challenge. Posttranslational modifications of histones, such as histone H3 lysine-27 trimethylation (H3K27me3) by the Polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells.

Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome.

Background: The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized.

Simplifying prediction of disease progression in pre-symptomatic type 1 diabetes using a single blood sample.

Aims/hypothesis: Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw.