These findings establish the importance of TMHS for normal sound transduction in humans.

Ezrin, radixin, and moesin are paralogous proteins that make up the ERM family and function as cross-linkers between integral membrane proteins and actin filaments of the cytoskeleton. In the mouse, a null allele of Rdx encoding radixin is associated with hearing loss as a result of the degeneration of inner ear hair cells as well as with hyperbilirubinemia due to hepatocyte dysfunction. Two mutant alleles of RDX [c.1732G>A (p.D578N) and c.1404_1405insG (p.A469fsX487)] segregating in two consanguineous Pakistani families are associated with neurosensory hearing loss. Both of these mutant alleles are predicted to affect the actin-binding motif of radixin. Sequence analysis of RDX in the DNA samples from the original DFNB24 family revealed a c.463C>T transition substitution that is predicted to truncate the protein in the FERM domain (F for 4.1, E for ezrin, R for radixin, and M for moesin) (p.Q155X). We also report a more complete gene and protein structure of RDX, including four additional exons and five new isoforms of RDX that are expressed in human retina and inner ear. Further, high-resolution confocal microscopy in mouse inner ear demonstrates that radixin is expressed along the length of stereocilia of hair cells from both the organ of Corti and the vestibular system.

A genome wide linkage analysis of nonsyndromic deafness segregating in a consanguineous Pakistani family (PKDF537) was used to identify DFNB63, a new locus for congenital profound sensorineural hearing loss. A maximum two-point lod score of 6.98 at theta = 0 was obtained for marker D11S1337 (68.55 cM). Genotyping of 550 families revealed three additional families (PKDF295, PKDF702 and PKDF817) segregating hearing loss linked to chromosome 11q13.2-q13.3. Meiotic recombination events in these four families define a critical interval of 4.81 cM bounded by markers D11S4113 (68.01 cM) and D11S4162 (72.82 cM), and SHANK2, FGF-3, TPCN2 and CTTN are among the candidate genes in this interval. Positional identification of this deafness gene should reveal a protein necessary for normal development and/or function of the auditory system.

No abstract

Proton particles comprise the most abundant ionizing radiation (IR) in outer space. These high energy particles are known to cause frequent double- and single-stranded DNA lesions that can lead to cancer and tumor formation. Understanding the mechanism of cellular response to proton-derived IR is vital for determining health risks to astronauts during space missions. Our understanding of the consequences of these high energy charged particles on microRNA (miRNA) regulation is still in infancy. miRNAs are non-coding, single-stranded RNAs of ~22 nucleotides that constitute a novel class of gene regulators. They regulate diverse biological processes, and each miRNA can control hundreds of gene targets. To investigate the effect of proton radiation on these master regulators, we examined the miRNA expression in selected mice organs that had been exposed to whole-body proton irradiation (2 Gy), and compared this to control mice (0 Gy exposure). RNA was isolated from three tissues (testis, brain, and liver) from treated and control mice and subjected to high-throughput small RNA sequencing. Bioinformatics analysis of small RNA sequencing data revealed dysregulation of (p < 0.05; 20 up- and 10 down-regulated) 14 mouse testis, 8 liver, and 8 brain miRNAs. The statistically significant and unique miRNA expression pattern found among three different proton-treated mouse tissues indicates a tissue-specific response to proton radiation. In addition to known miRNAs, sequencing revealed differential expression of 11 miRNAs in proton-irradiated mice that have not been previously reported in association with radiation exposure and cancer. The dysregulation of miRNAs on exposure to proton radiation suggest a possible mechanism of proton particles involvement in the onset of cell tumorgenesis. In summary, we have established that specific miRNAs are vulnerable to proton radiation, that such differential expression profile may depend upon the tissue, and that there are more miRNAs affected by proton radiation than have been previously observed.

AbstractLiver plays vital role in detoxification of exogenous and endogenous chemicals. These chemicals as well as oxidative stress may cause liver disorders. This study was aimed to evaluate the hepatoprotective effects of various fractions of Aconogonon alpinum methanolic extract against carbon tetrachloride (CCl4)-induced liver toxicity in mice. First, hepatoprotective potential of various fractions of A. alpinum was assessed and then antioxidant activity and profiling of polyphenolic compounds were assessed. A total of 78 male albino mice (BALB/c) were randomly divided into 13 groups (n = 6); Group I (normal control), Group II (CCl4 only), Group III (CCl4 + silymarin 100 mg/kg) and Groups IV–XIII (CCl4 + various fractions [200 and 400 mg/kg]). Hepatic biochemistry and liver injury were assessed by analysis of serum levels of hepatic enzymes and histopathological analysis, respectively. Results showed that polar fractions (ethyl acetate, n-butanol and aqueous fractions) exhibited highly significant (P < 0.01) reduction in increased level of liver biochemical parameters in a dose-dependent manner with consistent histopathological findings. Likewise, these fractions revealed strong antioxidant potential and polyphenolic compound contents. In conclusion, the present work has revealed promising antioxidant activity, polyphenolic profiling and potential hepatoprotective efficacy. Thus, the significant results unveil the study as a step forward towards evidence-based phytomedicine.

Livestock is an important commodity playing a major role in the global economy. Red meat plays an important role in human life, as it is a good source of animal protein and energy. The fatty acid content of beef has been shown to impact the eating experience and nutritional value of beef. Therefore, this study aimed to identify genomic regions which can account for genetic variation in meat fatty acid content. Genotypes imputed to the Illumina BovineHD 770K BeadChip were used in this study. Thirty-six 1-Mb genomic regions with a posterior probability of inclusion (PPI) greater than 0.90 were identified to be associated with variation in the content of at least one fatty acid. The genomic regions (1Mb) which were associated with more than one fatty acid trait with high genetic variance and harbored good candidate genes were on Chromosome (Chr) 6 (fatty acid binding protein 2), Chr 19 (thyroid hormone receptor alpha, fatty acid synthase), Chr 26 (stearoyl-CoA desaturase), and Chr 29 (thyroid hormone responsive, fatty acid desaturase 2, and fatty acid desaturase 3). Further studies are required to identify the causal variants within the identified genomic regions. Findings from the present study will help to increase understanding of the variation in fatty acid content of beef and help to enhance selection for beef with improved fatty acid composition.

A Single Tube Analysis system using LAMP, LED and ION-sensing (STALLION) for pathogen derived RNA/DNA.