OBJECTIVE:To compare diet and physical activity during pregnancy in women with and without type 1 diabetes and assess against national dietary guidelines. RESEARCH DESIGN AND METHODS:Diet and physical activity were measured prospectively in 1,124 pregnancies using validated questionnaires. RESULTS:Diets exceeded recommended intake for fat, saturated fat, discretionary foods, sodium, vitamin C, calcium, and zinc and were below recommendations for carbohydrate, fruit, dairy, vegetables, grain foods, and lean meats and alternatives. Differences in dietary intake between women with and without type 1 diabetes were modest. Total, moderate, and vigorous physical activity decreased in the third trimester. Women with type 1 diabetes performed less vigorous intensity activity than women without type 1 diabetes. CONCLUSIONS:Most pregnant women with and without type 1 diabetes did not meet dietary guidelines. Physical activity patterns were also mostly similar in women with and without type 1 diabetes.

Objective: Reduced microbial short-chain fatty-acids (SCFA) have been implicated in type-1-diabetes (T1D) risk. We investigated fecal SCFA concentrations in mother-infant dyads from pregnancy to the onset of islet autoimmunity (IA) to test whether decreased fecal SCFA concentrations increase islet autoimmunity (IA) risk. Research design and methods Children with a first-degree relative with T1D and their mothers were followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort study. A nested case-control design included n=54 infant-cases that developed  1 persistent islet autoantibodies/clinical T1D and n=161 age- and sex-matched controls without IA. Stool (n=1120 samples) from each pregnancy trimester in mothers (median n=2 samples) and from birth in infants (median n=6 samples) up until IA onset were used to quantify SCFAs by LC/MS. Weighted-conditional logistic-regression and linear mixed-effect models investigated associations between SCFAs and IA-onset. Results Fecal SCFAs were not associated with IA-onset, and SCFA profiles through pregnancy and early-childhood were similar between cases and controls. Infant fecal SCFA concentrations increased until age 1 year. Introduction of solid foods significantly increased acetate (FDR=0.000028) and summed primary SCFA (FDR=0.00784) concentrations. Higher infant BMI z-scores correlated with higher fecal acetate (FDR=0.0767) and butyrate (FDR=0.0590). Mothers with T1D had lower acetate (FDR=0.0696), butyrate (FDR=0.0959) and propionate (FDR=0.0696) than mothers without T1D during pregnancy. Concentrations of these three SCFA were lower in infants of mothers with versus without T1D (FDR=0.0073, FDR=0.0603, 0.0479, respectively). Conclusion These data do not support that lower fecal SCFA concentrations across pregnancy and early-life are directly associated with IA development.

This cohort study examines whether there is a temporal association between SARS-CoV-2 infection and the development of islet autoimmunity among Australian children with a first-degree relative with type 1 diabetes.

The vaginal microbiome has been linked to adverse pregnancy outcomes, which are markedly increased in women with type 1 diabetes. To investigate this relationship, we profiled the vaginal microbiome in pregnant women with and without type 1 diabetes, and in relation to pre-term birth (PTB) and pre-eclampsia (PE) in women with type 1 diabetes. Bacterial and fungal microbiomes were analysed by 16S rRNA gene and internal transcribed spacer 1 sequencing, respectively, in the third trimester of 310 pregnancies (160 with type 1 diabetes) for bacteria, and 147 pregnancies (70 with type 1 diabetes) for fungi. The vaginal microbiome was altered by type 1 diabetes in pregnancy, with an increase in the bacterial species Lactobacillus iners and Lactobacillus jensenii, and in the anaerobic genera Gardnerella, Anaerococcus, Prevotella, Dialister, Peptoniphilus and others that are associated with vaginal dysbiosis. In addition, the abundance of the fungal species Malassezia restricta was increased in women with type 1 diabetes. These changes were associated with increased risks of PTB and PE. PTB was associated with higher bacterial alpha diversity, decreased abundance of Lactobacillus reuteri, and increased abundance of Malassezia fungal genus, family Malasseziaceae and order Malasseziales. PE was associated with higher bacterial alpha diversity, increased abundance of Gardnerella vaginalis and decreased abundance of Candida albicans. Adverse pregnancy outcomes in women with type 1 diabetes are reflected by distinct changes in the vaginal microbiome. This highlights the importance of monitoring and managing the vaginal microbiome in high-risk pregnancies, particularly those complicated by type 1 diabetes. Early detection and treatment of risk-associated taxa, e.g. G. vaginalis in the case of PE, could potentially improve vaginal health and pregnancy outcomes in women with type 1 diabetes.

We aimed to assess perceived stress and influencing factors in mothers with children at risk of type 1 diabetes and coeliac disease who did, or did not, develop islet autoantibodies (IA) or coeliac autoantibodies (CA) by 4 years of age. Maternal perceived stress was assessed postpartum and when their child was approximately 4 years of age using the Perceived Stress Scale (range 1–56) in mothers followed prospectively in the multicentre Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy–birth cohort. Data were analysed using linear mixed models. In total, 818 mothers were included (642 children had no detected IA or CA [Ab negative], 97 had IA detected [IA positive] and 79 had CA detected [CA positive]). The development of IA or CA in young children did not add significantly to the perceived stress of their mothers at a median of 1.8 [IQR 0.8–2.5] and 1.6 [IQR 0.9–2.3] years later, respectively (Ab negative, adjusted predicted mean score 23.8 [95

Islet autoantibodies herald early type 1 diabetes. However, less is known of the evolution of autoantibodies to the islet autoantigen ZnT8. Our primary aim was to characterise the development of islet autoantibodies in a pregnancy–birth at-risk cohort and to provide new knowledge about ZnT8A. Islet autoantibodies were measured every 3–6 months in 1277/1473 children with a first-degree relative with type 1 diabetes who were followed prospectively from pregnancy in the Environmental Determinants of Islet Autoimmunity (ENDIA) cohort for 7.0 (IQR 5.8–8.3) years. Islet autoantibodies were also measured in the mothers and/or in cord blood in 901 pregnancies with type 1 diabetes. The development of persistent IAA reached a probability of 0.02 by 2 years of age. A combination of IAA- and GADA-first, GADA-first and ZnT8A-first all reached a similar probability by 5 years of age. ZnT8A appeared as the first islet autoantibody, alone or in combination, in 43 (32

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. We also compared dietary patterns in women with and without type 1 diabetes. Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a ‘fresh food’ dietary pattern than women without type 1 diabetes (OR 1.19, 95

Objective Continuous glucose monitoring (CGM) can detect early dysglycemia in older children and adults with pre-symptomatic type 1 diabetes and predict risk of progression to clinical onset. However, CGM data for very young children at greatest risk of disease progression are lacking. This study aimed to investigate the use of CGM data measured in children being longitudinally followed in the Australian Environmental Determinants of Islet Autoimmunity (ENDIA) study from birth to 10 years. Research Design and Methods Between January 2021 and June 2023, 31 ENDIA children with persistent multiple islet autoimmunity (PM Ab+) and 24 age-matched controls underwent CGM assessment alongside standard clinical monitoring. The CGM metrics of glucose standard deviation (SDSGL), coefficient of variation (CEV), mean sensor glucose (SGL) and percent time above 7.8 mmol/L (140mg/dL) were determined and examined for between group differences. Results The mean(SD) age of PM Ab+ and Ab- children was 4.4(1.8) and 4.7(1.9) years, respectively. Eighty-six percent of eligible PM Ab+ children consented to CGM wear, achieving a median[Q1,Q3] sensor wear period of 12.5[9.0, 15.0] days. PM Ab+ children had higher median[Q1,Q3] SDSGL (1.1[0.9,1.3] vs 0.9[0.8,1.0] (mmol/L); p<0.001) and CEV (17.3[16.0,20.9] vs 14.7[12.9,16.6](%); p<0.001). Percent time >7.8 mmol/L was greater in PM Ab+ children (median[Q1,Q3] 8.0 [4.4, 13.0] vs 3.3[1.4, 5.3] (%); p=0.005). Mean SGL did not differ significantly between groups (p=0.10). Conclusions CGM is feasible and well tolerated in very young type 1 diabetes at-risk children. Very young PM Ab+ children have increased SDSGL, CEV and percent time >7.8 mmol/L, consistent with prior studies involving older participants.

Soil salinity is a major environmental stressor affecting agricultural productivity worldwide. Understanding plant responses to salt stress is crucial for developing resilient crop varieties. Wild relatives of cultivated crops, such as wild tomato, Solanum pimpinellifolium, can serve as a useful resource to further expand the resilience potential of the cultivated germplasm, S. lycopersicum. In this study, we employed high-throughput phenotyping in the greenhouse and field conditions to explore salt stress responses of a S. pimpinellifolium diversity panel. Our study revealed extensive phenotypic variations in response to salt stress, with traits such as transpiration rate, shoot mass, and ion accumulation showing significant correlations with plant performance. We found that while transpiration was a key determinant of plant performance in the greenhouse, shoot mass strongly correlated with yield under field conditions. Conversely, ion accumulation was the least influential factor under greenhouse conditions. Through a Genome Wide Association Study, we identified candidate genes not previously associated with salt stress, highlighting the power of high-throughput phenotyping in uncovering novel aspects of plant stress responses. This study contributes to our understanding of salt stress tolerance in S. pimpinellifolium and lays the groundwork for further investigations into the genetic basis of these traits, ultimately informing breeding efforts for salinity tolerance in tomato and other crops.

Fertility is economically important but is hard to quantify and measure in breeding programs which has led extensive breeding programs to ignore fertility in their selection criteria. While female fertility traits have been extensively researched, male fertility traits have been largely ignored. It is estimated that 20% to 40% of bulls have sub-fertility, reducing the number of calves born and profits, highlighting the importance of investigating bull fertility. The most practical measure of male fertility is a bull breeding soundness evaluation (BBSE) which assesses structure as well as semen quality and quantity. Generally, traits recorded in a BBSE are neither genetically evaluated nor used for selection in breeding programs. All traits recorded during a BBSE were analyzed through a series of univariate and bivariate linear mixed models using a genomic relationship matrix to estimate genetic parameters. All genotype and phenotype data were obtained from a tropical composite commercial cattle population and imputed to 27,638 single-nucleotide polymorphisms (SNPs) with a total of 2,613 genotyped animals with BBSE records ranging from 616 to 826 animals depending on the trait. The heritabilities of the 27 traits recorded during a BBSE ranged from 0.02 to 0.49. Seven of the male fertility traits were recommended to be included in a breeding program based on their heritability and their phenotypic and genetic correlations. These traits are scrotal circumference, percent normal sperm, proximal droplets, distal midpiece reflex, knobbed acrosomes, vacuoles/teratoids, and sheath score. Using these seven traits in a breeding program would result in higher calving rates, increasing production and profitability.

Context Reproduction is an economically important trait in both males and females; however, the relationships between fertility and body composition traits are little researched, but essential to breeding programs, as they will help inform selection decisions and allow the greatest opportunity for genetic gain. Aims Estimate genetic and phenotypic correlations between male and female yearling fertility traits and investigate their relationship with yearling body composition traits, which have an effect on the attainment of puberty. Methods Genotype and phenotype data were obtained from a tropical composite commercial cattle population and imputed to 27 638 single nucleotide polymorphisms. A series of univariate and bivariate linear mixed models using a genomic relationship matrix were run to estimate genetic parameters, genetic and phenotypic correlations for a series of male and female fertility and body composition traits. These parameters were then compared to help understand the genetic relationships. Key results Scrotal circumference was favourably genetically correlated with weight (0.34), fat traits (0.06–0.24), muscle (0.24) and heifer days to calving (−0.32). Heifer days to calving was favourably correlated with muscle (−0.18) but not fat traits (0.11 to 0.21). The genetic correlations between heifer days to calving and sperm morphology traits were generally unfavourable (−0.32 to 0.25). Sperm morphology traits were favourably genetically correlated with fat traits (−0.84 to 0.31) and muscle (−0.61 to 0.31) but not weight (−0.15 to 0.09). Conclusions and implications Yearling sperm morphology traits were unfavourably correlated with heifer days to calving, indicating that they are not good candidates for indirect selection on improving female fertility in the herd. A different trend was found for yearling scrotal circumference and heifer days to calving, identifying it as a good candidate for indirect selection of heifer fertility as it is easy to measure and heritable. The genetic correlations estimated between composition traits with male and female fertility traits allow breeding programs to make an informed selection decision to optimise genetic gain across all traits.

Barley is a major cereal crop for temperate climates, and a diploid genetic model for polyploid wheat. Cereal straw biomass is an attractive source of feedstock for green technologies but lignin, a key determinant of feedstock recalcitrance, complicates bio-conversion processes. However, manipulating lignin content to improve the conversion process could negatively affect agronomic traits. An alternative approach is to manipulate lignin composition which influences the physical and chemical properties of straw. This study validates the function of a barley ferulate 5-hydroxylase gene and demonstrates that its downregulation using the RNA-interference approach substantially impacts lignin composition. We identified five barley genes having putative ferulate 5-hydroxylase activity. Downregulation of HvF5H1 substantially reduced the lignin syringyl/guaiacyl (S/G) ratio in straw while the lignin content, straw mechanical properties, plant growth habit, and grain characteristics all remained unaffected. Metabolic profiling revealed significant changes in the abundance of 173 features in the HvF5H1-RNAi lines. The drastic changes in the lignin polymer of transgenic lines highlight the plasticity of barley lignification processes and the associated potential for manipulating and improving lignocellulosic biomass as a feedstock for green technologies. On the other hand, our results highlight some differences between the lignin biosynthetic pathway in barley, a temperate climate grass, and the warm climate grass, rice, and underscore potential diversity in the lignin biosynthetic pathways in grasses.

Female fertility is essential to any beef breeding program. However, little genetic gain has been made due to long generation intervals and low levels of phenotyping. Days to calving (DC) is a fertility trait that may provide genetic gain and lead to an increased weaning rate. Genetic parameters and correlations were estimated and compared for DC across multiple joinings (first, second and third+) and lactation status (lactating and non-lactating) for a tropical composite cattle population where cattle were first mated as yearlings. The genetic correlation between first joining DC and mature joining DC (third+) was moderate–high (0.55–0.83). DC was uncorrelated between multiparous lactating and non-lactating cows (rG = −0.10). Mature joining DC was more strongly correlated with second joining lactating DC (0.41–0.69) than with second joining non-lactating DC (−0.14 to −0.16). Thus, first joining DC, second joining DC and mature joining DC should be treated as different traits to maximise genetic gain. Further, for multi-parous cows, lactating and non-lactating DC should be treated as different traits. Three traits were developed to report back to the breeding programs to maximise genetic gain: the first joining days to calving, the second joining days to calving lactating and mature days to calving lactating.

Abstract Background: 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. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D. Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case’s onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood. Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation. KEY MESSAGES The ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.

ABSTRACT 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. Materials and Methods Sera were collected 3 monthly from birth from children with a first‐degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosa‐associated cytokines IL‐21, IL‐22, IL‐25, and IL‐10, the Th17‐related cytokines IL‐17F and IL‐23, as well as IL‐33, IFN‐γ, and IL‐4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex‐ and age‐matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa‐associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity.

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. We also investigated whether engagement with Facebook content was associated with specific post themes.METHODS:Characteristics of Facebook versus conventional recruits were compared using linear, logistic, and multinomial logistic regression models. Logistic regression was used to determine the risk of study withdrawal. Data pertaining to 794 Facebook posts over 7.5 years were included in the analysis.RESULTS:Facebook was the third largest source of referral (300/1511; 19.9%). Facebook recruits were more frequently Australian-born (P < .001) enrolling postnatally (P = .01) and withdrew from the study at a significantly lower rate compared with conventional recruits (4.7% vs 12.3%; P < .001) after a median of follow-up of 3.3 years. Facebook content featuring stories and images of participants received the highest engagement even though <20% of the 2337 Facebook followers were enrolled in the study.CONCLUSIONS:Facebook was a valuable recruitment tool for ENDIA. Compared with conventional recruits, Facebook recruits were three times less likely to withdraw during long-term follow-up and had different sociodemographic characteristics. Facebook content featuring participants was the most engaging. These findings inform social media strategies for future cohort and type 1 diabetes studies.TRIAL REGISTRATION:Australia New Zealand Clinical Trials Registry: ACTRN1261300794707.

AbstractSoil salinity is a major environmental stressor affecting agricultural productivity worldwide. Understanding plant responses to salt stress is crucial for developing resilient crop varieties. Wild relatives of cultivated crops, such as wild tomato,Solanum pimpinellifolium, can serve as a useful resource to further expand the resilience potential of the cultivated germplasm,S. lycopersicum. In this study, we employed high-throughput phenotyping in the greenhouse and field conditions to explore salt stress responses of aS. pimpinellifoliumdiversity panel. Our study revealed extensive phenotypic variations in response to salt stress, with traits such as transpiration rate, shoot mass, and ion accumulation showing significant correlations with plant performance. We found that while transpiration was a key determinant of plant performance in the greenhouse, shoot mass strongly correlated with yield under field conditions. Conversely, ion accumulation was the least influential factor under greenhouse conditions. Through a Genome Wide Association Study, we identified candidate genes not previously associated with salt stress, highlighting the power of high-throughput phenotyping in uncovering novel aspects of plant stress responses. This study contributes to our understanding of salt stress tolerance inS. pimpinellifoliumand lays the groundwork for further investigations into the genetic basis of these traits, ultimately informing breeding efforts for salinity tolerance in tomato and other crops.

A comparison of lifestyle during pregnancy against Australian recommendations of women with and without type 1 diabetes from the Environmental Determinants of Islet Autoimmunity study - Volume 82 Issue OCE2

Background: We sought research experiences of caregivers and their children were enrolled in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Methods: ENDIA is a pregnancy–birth cohort investigating early-life causes of type 1 diabetes (T1D). Surveys were sent to 1090 families between June 2021 and March 2022 with a median participation of >5 years. Caregivers completed a 12-item survey. Children ≥ 3 years completed a four-item survey. Results: The surveys were completed by 550/1090 families (50.5%) and 324/847 children (38.3%). The research experience was rated as either “excellent” or “good” by 95% of caregivers, and 81% of children were either “ok”, “happy” or “very happy”. The caregivers were motivated by contributing to research and monitoring their children for T1D. Relationships with the research staff influenced the experience. The children most liked virtual reality headsets, toys, and “helping”. Blood tests were least liked by the children and were the foremost reason that 23.4% of the caregivers considered withdrawing. The children valued gifts more than their caregivers. Only 5.9% of responses indicated dissatisfaction with some aspects of the protocol. The self-collection of samples in regional areas, or during the COVID-19 pandemic restrictions, were accepted. Conclusions: This evaluation identified modifiable protocol elements and was conducted to further improve satisfaction. What was important to the children was distinct from their caregivers.

Imputation can be used to obtain a large number of high-density genotypes at the cost of procuring low-density panels. Accurate imputation requires a well-formed reference population of high-density genotypes to enable statistical inference. Five methods were compared using commercial Wagyu genotype data to identify individuals to produce a “well-formed” reference population. Two methods utilised a relationship matrix (MCG and MCA), two of which utilised a haplotype block library (AHAP2 and IWS), and the last selected high influential sires with greater than 10 progeny (PROG). The efficacy of the methods was assessed based on the total proportion of genetic variance accounted for and the number of haplotypes captured, as well as practical considerations in implementing these methods. Concordance was high between the MCG and MCA and between AHAP2 and IWS but was low between these groupings. PROG-selected animals were most similar to MCA. MCG accounted for the greatest proportion of genetic variance in the population (35%, while the other methods accounted for approximately 30%) and the greatest number of unique haplotypes when a frequency threshold was applied. MCG was also relatively simple to implement, although modifications need to be made to account for DNA availability when running over a whole population. Of the methods compared, MCG is the recommended starting point for an ongoing sequencing project.