FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs

Identification and characterization of an inhibitory fibroblast growth factor receptor 2 (FGFR2) molecule, up-regulated in an Apert Syndrome mouse model

AS (Apert syndrome) is a congenital disease composed of skeletal, visceral and neural abnormalities, caused by dominant-acting mutations in FGFR2 [FGF (fibroblast growth factor) receptor 2]. Multiple FGFR2 splice variants are generated through alternative splicing, including PTC (premature termination codon)-containing transcripts that are normally eliminated via the NMD (nonsense-mediated decay) pathway. We have discovered that a soluble truncated FGFR2 molecule encoded by a PTC-containing transcript is up-regulated and persists in tissues of an AS mouse model. We have termed this IIIa–TM as it arises from aberrant splicing of FGFR2 exon 7 (IIIa) into exon 10 [TM (transmembrane domain)]. IIIa–TM is glycosylated and can modulate the binding of FGF1 to FGFR2 molecules in BIAcore-binding assays. We also show that IIIa–TM can negatively regulate FGF signalling in vitro and in vivo. AS phenotypes are thought to result from gain-of-FGFR2 signalling, but our findings suggest that IIIa–TM can contribute to these through a loss-of-FGFR2 function mechanism. Moreover, our findings raise the interesting possibility that FGFR2 signalling may be a regulator of the NMD pathway

A role for Dicer in immune regulation

Micro RNAs (miRNAs) regulate gene expression at the posttranscriptional level. Here we show that regulatory T (T reg) cells have a miRNA profile distinct from conventional CD4 T cells. A partial T reg cell–like miRNA profile is conferred by the enforced expression of Foxp3 and, surprisingly, by the activation of conventional CD4 T cells. Depleting miRNAs by eliminating Dicer, the RNAse III enzyme that generates functional miRNAs, reduces T reg cell numbers and results in immune pathology. Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor β. These results suggest that T reg cell development involves Dicer-generated RNAs

Cross-Sectional Associations between Dietary Fat-Related Behaviors and Continuous Metabolic Syndrome Score among Young Australian Adults

Dietary guidelines recommend removing visible fat from meat, choosing low-fat options and cooking with oil instead of butter. This study examined cross-sectional associations between fat-related eating behaviors and a continuous metabolic syndrome (cMetSyn) score among young adults. During 2004-2006, 2071 participants aged 26-36 years reported how often they trimmed fat from meat, consumed low-fat dairy products and used different types of fat for cooking. A fasting blood sample was collected. Blood pressure, weight and height were measured. To create the cMetSyn score, sex-specific principal component analysis was applied to normalized risk factors of the harmonized definition of metabolic syndrome. Higher score indicates higher risk. For each behavior, differences in mean cMetSyn score were calculated using linear regression adjusted for confounders. Analyses were stratified by weight status (Body mass index (BMI) < 25 kg/m(2) or 25 kg/m(2)). Mean cMetSyn score was positively associated with consumption of low-fat oily dressing (P-Trend = 0.013) among participants who were healthy weight and frequency of using canola/sunflower oil for cooking (P-Trend = 0.008) among participants who were overweight/obese. Trimming fat from meat, cooking with olive oil, cooking with butter, and consuming low-fat dairy products were not associated with cMetSyn score. Among young adults, following fat-related dietary recommendations tended to not be associated with metabolic risk

The metabolomic signatures of alcohol consumption in young adults

BackgroundMetabolomic analysis may help us to understand the association between alcohol consumption and cardio-metabolic health. We aimed to: (i) replicate a previous study of alcohol consumption and metabolic profiles, (ii) examine associations between types of alcoholic beverages and metabolites and (iii) include potential confounders not examined in previous studies.MethodsCross-sectional data of 1785 participants (age 26–36 years, 52% women) from the 2004–2006 Childhood Determinants of Adult Health study were used. Consumption of beer, wine and spirits was assessed by questionnaires. Metabolites were measured by a high-throughput nuclear magnetic resonance platform and multivariable linear regression examined their association with alcohol consumption (combined total and types) adjusted for covariates including socio-demographics, health behaviours and mental health.ResultsAlcohol consumption was associated with 23 out of 37 lipids, 12 out of 16 fatty acids and six out of 20 low-molecular-weight metabolites independent of confounders with similar associations for combined total alcohol consumption and different types of alcohol. Many metabolites (lipoprotein lipids in high-density lipoprotein (HDL) subclasses, HDL cholesterol, apolipoprotein A-1, phosphotriglycerides, total fatty acids, monounsaturated fatty acids, omega-3 fatty acids) had positive linear associations with alcohol consumption but some showed negative linear (low-density lipoprotein particle size, omega-6 fatty acids ratio to total fatty acids, citrate) or U-shaped (lipoprotein lipids in very-low-density lipoprotein (VLDL) subclasses, VLDL triglycerides) associations.ConclusionsOur results were similar to those of the only previous study. Associations with metabolites were similar for total and types of alcohol. Alcohol consumption in young adults is related to a diverse range of metabolomic signatures associated with benefits and harms to health.</p

High-resolution Local Gravity Model of the South Pole of the Moon from GRAIL Extended Mission Data

We estimated a high-resolution local gravity field model over the south pole of the Moon using data from the Gravity Recovery and Interior Laboratory's extended mission. Our solution consists of adjustments with respect to a global model expressed in spherical harmonics. The adjustments are expressed as gridded gravity anomalies with a resolution of 1/6deg by 1/6deg (equivalent to that of a degree and order 1080 model in spherical harmonics), covering a cap over the south pole with a radius of 40deg. The gravity anomalies have been estimated from a short-arc analysis using only Ka-band range-rate (KBRR) data over the area of interest. We apply a neighbor-smoothing constraint to our solution. Our local model removes striping present in the global model; it reduces the misfit to the KBRR data and improves correlations with topography to higher degrees than current global models

The chicken talpid3 gene encodes a novel protein that is essential for hedgehog signaling

Talpid(3) is a classical chicken mutant with abnormal limb patterning and malformations in other regions of the embryo known to depend on Hedgehog signaling. We combined the ease of manipulating chicken embryos with emerging knowledge of the chicken genome to reveal directly the basis of defective Hedgehog signal transduction in talpid(3) embryos and to identify the talpid(3) gene. We show in several regions of the embryo that the talpid(3) phenotype is completely ligand independent and demonstrate for the first time that talpid(3) is absolutely required for the function of both Gli repressor and activator in the intracellular Hedgehog pathway. We map the talpid(3) locus to chromosome 5 and find a frameshift mutation in a KIAA0586 ortholog (ENSGALG00000012025), a gene not previously attributed with any known function. We show a direct causal link between KIAA0586 and the mutant phenotype by rescue experiments. KIAA0586 encodes a novel protein, apparently specific to vertebrates, that localizes to the cytoplasm. We show that Gli3 processing is abnormal in talpid(3) mutant cells but that Gli3 can still translocate to the nucleus. These results suggest that the talpid(3) protein operates in the cytoplasm to regulate the activity of both Gli repressor and activator proteins

Global and Local Gravity Field Models of the Moon Using GRAIL Primary and Extended Mission Data

The Gravity Recovery and Interior Laboratory (GRAIL) mission was designed to map the structure of the lunar interior from crust to core and to advance the understanding of the Moon's thermal evolution by producing a high-quality, high-resolution map of the gravitational field of the Moon. The mission consisted of two spacecraft, which were launched in September 2011 on a Discovery-class NASA mission. Ka-band tracking between the two satellites was the single science instrument, augmented by tracking from Earth using the Deep Space Network (DSN)

Multiple Sclerosis risk variants regulate gene expression in innate and adaptive immune cells

At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS

Retrospectively Estimating Energy Intake and Misreporting From a Qualitative Food Frequency Questionnaire: An Example Using Australian Cohort and National Survey Data

Qualitative food frequency questionnaires (Q-FFQ) omit portion size information from dietary assessment. This restricts researchers to consumption frequency data, limiting investigations of dietary composition (i.e., energy-adjusted intakes) and misreporting. To support such researchers, we provide an instructive example of Q-FFQ energy intake estimation that derives typical portion size information from a reference survey population and evaluates misreporting. A sample of 1,919 Childhood Determinants of Adult Health Study (CDAH) participants aged 26-36 years completed a 127-item Q-FFQ. We assumed sex-specific portion sizes for Q-FFQ items using 24-h dietary recall data from the 2011-2012 Australian National Nutrition and Physical Activity Survey (NNPAS) and compiled energy density values primarily using the Australian Food Composition Database. Total energy intake estimation was daily equivalent frequency x portion size (g) x energy density (kJ/g) for each Q-FFQ item, summed. We benchmarked energy intake estimates against a weighted sample of age-matched NNPAS respondents (n = 1,383). Median (interquartile range) energy intake was 9,400 (7,580-11,969) kJ/day in CDAH and 9,055 (6,916-11,825) kJ/day in weighted NNPAS. Median energy intake to basal metabolic rate ratios were 1.43 (1.15-1.78) in CDAH and 1.35 (1.03-1.74) in weighted NNPAS, indicating notable underreporting in both samples, with increased levels of underreporting among the overweight and obese. Using the Goldberg and predicted total energy expenditure methods for classifying misreporting, 65 and 41% of CDAH participants had acceptable/plausible energy intake estimates, respectively. Excluding suspected CDAH misreporters improved the plausibility of energy intake estimates, concordant with expected body weight associations. This process can assist researchers wanting an estimate of energy intake from a Q-FFQ and to evaluate misreporting, broadening the scope of diet-disease investigations that depend on consumption frequency data