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MITF is a known gene underlying autosomal dominant hearing loss, Waardenburg syndrome (WS). Biallelic MITF mutations have been found associated with a rare hearing loss syndrome consisting eye abnormalities and albinism; and a more severe type of WS whose heterozygous parents were affected with classic WS in both cases. The aims of this study were to identify a new candidate gene causing autosomal recessive nonsyndromic hearing loss (ARNSHL) and confirm its causation by finding additional families affected with the candidate gene and supporting evidences from functional analyses. By using whole exome sequencing, we identified a homozygous c.1022G>A p.Arg341His variant of MITF, which co-segregated with the hearing loss in five affected children of a consanguineous hearing couple. Targeted exome sequencing in a cohort of 130 NSHL individuals, using our in-house gene panel revealed a second family with c.1021C>T p.Arg341Cys MITF variant. Functional studies confirmed that the Arg341His and Arg341Cys alleles yielded a normal sized MITF protein, with aberrant cytosolic localization as supported by the molecular model and the reporter assay. In conclusion, we demonstrate MITF as a new cause of ARNSHL, with heterozygous individuals free of symptoms. MITF should be included in clinical testing for NSHL, though it is rare.Brain organoids are promising tools for disease modeling and drug development. For proper neuronal network formation excitatory and inhibitory neurons as well as glia need to co-develop. Here, we report the directed self-organization of human induced pluripotent stem cells in a collagen hydrogel towards a highly interconnected neuronal network at a macroscale tissue format. Bioengineered Neuronal Organoids (BENOs) comprise interconnected excitatory and inhibitory neurons with supportive astrocytes and oligodendrocytes. Giant depolarizing potential (GDP)-like events observed in early BENO cultures mimic early network activity of the fetal brain. The observed GABA polarity switch and reduced GDPs in >40 day BENO indicate progressive neuronal network maturation. BENOs demonstrate expedited complex network burst development after two months and evidence for long-term potentiation. The similarity of structural and functional properties to the fetal brain may allow for the application of BENOs in studies of neuronal plasticity and modeling of disease.This study aimed to analyse the effect of playing surface temperature on muscular and thermal response to a repeated-sprint ability (RSA) test in football players. Thirty-two male football players (23 ± 5 years; 1.77 ± 0.06 m; 71.2 ± 6.7 kg) from two squads of a third-division football club participated in the study. An RSA test was carried out at a high surface temperature (45.34 ± 2.53 °C) and low surface temperature (27.21 ± 2.17 °C). Before and after this test, the muscular response of the players was assessed through tensiomyography and thermograms. The results revealed that performance in the RSA test particularly increased at a higher surface temperature, especially in the first 5 m of the 30 m sprint test. While a reduction in maximal radial displacement (Dm) in the biceps femoris post-RSA was observed at lower surface temperatures, a higher temperature on the thigh, hamstring and calf was found in the higher surface temperature group. In conclusion, higher surface temperatures had an influence on players' thermal and tensiomyographic profile and improved performance in their repeated-sprint ability. These results suggest a need for coaches and players to be aware of these parameters to ensure adequate functionality and safety of the playing surface.Endogenous antimicrobial peptides (AMPs) are evolutionarily ancient factors of innate immunity, which are produced by all multicellular organisms and play a key role in their protection against infection. Red king crab (Paralithodes camtschaticus), also called Kamchatka crab, is widely distributed and the best known species of all king crabs belonging to the family Lithodidae. Selleck 17-OH PREG Despite their economic importance, the genetic resources of king crabs are scarcely known and no full-genome sequences are available to date. Therefore, analysis of the red king crab transcriptome and identification and characterization of its AMPs could potentially contribute to the development of novel antimicrobial drug candidates when antibiotic resistance has become a global health threat. In this study, we sequenced the P. camtschaticus transcriptomes from carapace, tail flap and leg tissues using an Illumina NGS platform. Libraries were systematically analyzed for gene expression profiles along with AMP prediction. By an in silico approach using public databases we defined 49 cDNAs encoding for AMP candidates belonging to diverse families and functional classes, including buforins, crustins, paralithocins, and ALFs (anti-lipopolysaccharide factors). We analyzed expression patterns of 27 AMP genes. The highest expression was found for Paralithocin 1 and Crustin 3, with more than 8,000 reads. Other paralithocins, ALFs, crustins and ubiquicidins were among medium expressed genes. This transcriptome data set and AMPs provide a solid baseline for further functional analysis in P. camtschaticus. Results from the current study contribute also to the future application of red king crab as a bio-resource in addition to its being a known seafood delicacy.This study evidenced the presence of parasites in a cesspit of an aristocratic palace of nineteenth century in Sardinia (Italy) by the use of classical paleoparasitological techniques coupled with next-generation sequencing. Parasite eggs identified by microscopy included helminth genera pathogenic for humans and animals the whipworm Trichuris sp., the roundworm Ascaris sp., the flatworm Dicrocoelium sp. and the fish tapeworm Diphyllobothrium sp. In addition, 18S rRNA metabarcoding and metagenomic sequencing analysis allowed the first description in Sardinia of aDNA of the human specific T. trichiura species and Ascaris genus. Their presence is important for understanding the health conditions, hygiene habits, agricultural practices and the diet of the local inhabitants in the period under study.
Website: https://www.selleckchem.com/products/17-oh-preg.html
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