Smedhyde3862

Maturity-onset diabetes of the young (MODY) 8 is a rare form of monogenic diabetes characterized by a mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed by β cell failure. Induced pluripotent stem cells can differentiate into functional β cells. Thus, β cells from MODY8 patients can be generated in vitro and used for disease modelling and cell replacement therapy.

A genetic study was performed in a patient suspected of monogenic diabetes.

A novel heterozygous pathogenic variant in CEL (c.1818delC) was identified in the proband, allowing diagnosis of MODY8. Three MODY8-iPSC (induced pluripotent stem cell) clones were reprogrammed from skin fibroblasts of the patient, and their pluripotency and genomic stability confirmed. All 3 MODY8-iPSC differentiated into β cells following developmental stages. MODY8-iPSC-derived β cells were able to secrete insulin upon glucose dynamic perifusion. The CEL gene was not expressed in iPSCs nor during any steps of endocrine differentiation.

iPSC lines from a MODY8 patient with a novel pathogenic variant in the CEL gene were generated; they are capable of differentiation into endocrine cells, and β cell function is preserved in mutated cells. These results set the basis for in vitro modelling of the disease and potentially for autologous β cell replacement.

iPSC lines from a MODY8 patient with a novel pathogenic variant in the CEL gene were generated; they are capable of differentiation into endocrine cells, and β cell function is preserved in mutated cells. These results set the basis for in vitro modelling of the disease and potentially for autologous β cell replacement.Genomic selection relies on single nucleotide polymorphisms (SNP), which are often collected using medium-density SNP arrays. In mink, no such array is available; instead, genotyping by sequencing (GBS) can be used to generate marker information. Here, we evaluated the effect of genomic selection for mink using GBS. We compared the estimated breeding values (EBV) from single-step genomic best linear unbiased prediction models (SSGBLUP) to the EBV from ordinary pedigree-based BLUP models. We analyzed seven size and quality traits from the live grading of brown mink. The phenotype data consisted of ~20,600 records for the seven traits from the mink born between 2013 and 2016. Genotype data included 2,103 mink born between 2010 and 2014, mostly breeding animals. In total, 28,336 SNP markers from 391 scaffolds were available for genomic prediction. The pedigree file included 29,212 mink. The predictive ability was assessed by the correlation (r) between progeny trait deviation (PTD) and EBV, and the regression ofiction in mink, demonstrating the potential of GBS for genomic selection in livestock species.

To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers.

We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE.

Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%-26%).

We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.

Chronic intermittent hypoxia (CIH) is a major determinant in OSA cardiovascular morbidity and this effect is influenced by age. The objective of the present study was to assess the differential molecular mechanisms at gene level expression involved in the cardiovascular remodeling induced by CIH according to chronological age.

Two-month and 18-month old mice (N=8 each) were subjected to CIH or normoxia for 8-weeks. Total mRNA was extracted from left ventricle myocardium and aortic arch, and gene expression of 46 intermediaries of aging, oxidative stress and inflammation was measured by quantitative real time PCR.

Cardiac gene expression of Nrf2 (2.05-fold increase, p<0.001), Sod2 (1.9-fold increase, p=0.035), Igf1r (1.4-fold increase, p=0.028), Mtor (1.8-fold increase, p=0.06), Foxo3 (1.5-fold increase, p=0.020), Sirt4, Sirt6, and Sirt7 (1.3-fold increase, p=0.012; 1.1-fold change, p=0.031; 1.3-fold change, p=0.029) was increased after CIH in young mice, but not in old mice. In aortic tissue, eNOS was reduced in young mice (p<0.001), Nrf2 was reduced in 80% (p<0.001) in young mice and in 45% (p=0.07) in old mice, as its downstream antioxidant target Sod2 (82% reduced, p<0.001). IL33.

CIH effect in gene expression is organ-dependent, and is modulated by age. PD-L1 inhibitor CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a pro-aging process.

CIH effect in gene expression is organ-dependent, and is modulated by age. CIH increased transcriptional expression of genes involved in cardioprotection and cell survival in young, but not in old mice. In aortic tissue, CIH reduced gene expression related to an antioxidant response in both young and old mice, suggesting vascular oxidative stress and a pro-aging process.