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Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg2+-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo. Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3' genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3'-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3'-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3' ends.

Aim: We investigated associations between body mass index (BMI) z‐scores for children aged 0–2 years and the BMI z‐scores, body fat percentage and metabolic risk factors at 3 years of age. Methods: This was a secondary analysis of the Lifestyle in Pregnancy and Offspring randomised controlled trial, carried out at two university hospitals in Denmark. It comprised 149 mothers with BMI ≥30 kg/m2 who did or did not receive a lifestyle intervention during pregnancy and a reference group of 97 mothers with normal‐weight, with follow‐up of their 3‐year‐old offspring. The children in these three groups were pooled for the data analyses, due to similar characteristics between groups. The BMI z‐scores were calculated at 5 weeks, 5 months and 1, 2 and 3 years, using Danish reference groups. Their anthropometrics and metabolic outcomes were examined at 3 years of age. Results: BMI z‐scores at 5 months to 2 years were associated with BMI z‐scores and body fat percentage at 3 years of age and BMI z‐scores were not associated with metabolic risk factors at 3 years. Conclusion: BMI z‐scores from 5 weeks of age were associated with adverse anthropometric outcomes but not with metabolic risk factors at 3 years of age. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between cord 25-hydroxyvitamin D2+3 (25(OH)D) and attention deficit hyperactivity disorder symptoms in toddlers, using Child Behaviour Checklist for ages 1.5-5. Method: In a population-based birth cohort, a Child Behaviour Checklist for ages 1.5-5 questionnaire was returned from parents of 1233 infants with mean age 2.7 (standard deviation 0.6) years. Adjusted associations between cord 25(OH)D and Child Behaviour Checklist-based attention deficit hyperactivity disorder problems were analysed by multiple regression. Results: The median cord 25(OH)D was 44.1 (range: 1.5-127.1) nmol/L. Mean attention deficit hyperactivity disorder problem score was 2.7 (standard deviation 2.1). In adjusted analyses, cord 25(OH)D levels >25 nmol/L and >30 nmol/L were associated with lower attention deficit hyperactivity disorder scores compared to levels ≤25 nmol/L (ρ = 0.035) and ≤30 nmol/L (ρ = 0.043), respectively. The adjusted odds of scoring above the 90th percentile on the Child Behaviour Checklist-based attention deficit hyperactivity disorder problem scale decreased by 11% per 10 nmol/L increase in cord 25(OH)D. Conclusion: An inverse association between cord 25(OH)D and attention deficit hyperactivity disorder symptoms in toddlers was found, suggesting a protective effect of prenatal vitamin D. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. Several studies have shown that vitamin D levels can affect levels of circulating FoxP3-positive regulatory T-lymphocytes. Previously, our group has demonstrated that adoptive transfer of FoxP3-positive T-lymphocytes ameliorated the phenotype in a mouse model of angiotensin-II induced cardiac damage.Objective: To investigate the impact of vitamin D depletion in a transgenic rat model of angiotensin II-mediated hypertensive organ failure, and to investigate the possible association with levels of FoxP3 regulatory T-lymphocytes.Methods: In 4-week old age-matched rats overexpressing the human renin and angiotensinogen genes, group 1 (n=18) received vitamin D depleted chow, and group 2, (n=15) received chow with standard contents of vitamin D. Blood pressure (tail cuff) and 24-hour albuminuria were determined once weekly. After three weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. Lymphocytes from spleens were isolated, and the percentage of CD4+ cells, which were CD4+CD25+FoxP3-positive, was measured by flow cytometry. Mesenteric arteries were removed and stimulated with nitroprusside and acetylcholine to investigate the relaxation potential of the epithelium.Results: The vitamin D depleted group had higher blood pressure at all times (mean differences were 23.40 mmHg, 14.31 mmHg and 15.71 mmHg respectively, p<0.05), higher heart-to-body weight ratio, and higher ANP and BNP levels. No differences were found between groups in mortality or proteinuria. Neither the levels of CD4+CD25+FoxP3-positive cells in spleen, nor the relaxation potential measured in mesenteric arteries differed between groups.Conclusion: Short-term vitamin D depletion aggravated hypertension and end-organ damage in a rat model of angiotensin II-induced hypertension. However, the aggravated phenotype was not due to different levels of splenic FoxP3-positive activated T-lymphocytes or to higher endothelial resistance in arteries. [ABSTRACT FROM AUTHOR]

This is a description of two cases of subcutaneous fat necrosis due to asphyxia in two newborns, and associated hypercalcaemia. Treatment with intravenous pamidronate 0.5 mg/kg for three days was very successful and well-tolerated. In conclusion, the treatment of hypercalcaemia was effective, but requires continuous control for a longer period of time due to the risk of fluctuating serum calcium levels.