Variants of OTOF and PJVK Genes in Chinese Patients with Auditory Neuropathy Spectrum Disorder

BACKGROUND: Mutations in OTOF and PJVK genes cause DFNB9 and DFNB59 types of hearing loss, respectively. The patients carrying pathogenic mutations in either of these genes may show the typical phenotype of auditory neuropathy spectrum disorder (ANSD). The aim of the present study was to identify OTOF and PJVK mutations in sporadic ANSD patients. METHODS AND FINDINGS: A total of 76 unrelated Chinese non-syndromic ANSD patients were sequenced on the gene OTOF and PJVK exon by exon. Variants were valued in 105 controls with normal hearing to verify the carrying rate. We identified one pathogenic mutation (c.1194T>A) and three novel, possibly pathogenic, variants (c.3570+2T>C, c.4023+1 G>A, and c.1102G>A) in the OTOF gene, and one novel, possibly pathogenic, variant (c.548G>A) in PJVK. Moreover, we found three novel missense mutations within the exons of OTOF. CONCLUSIONS: As we identified 4 and 1 possible pathogenic variants of the OTOF gene and the PJVK gene, respectively, we believe that screening in these genes are important in sporadic ANSD patients. The pathogenicity of these novel mutations needs further study because of their single heterozygous nature. Knowledge on the mutation spectra of these genes in Chinese would be beneficial in understanding the genetic character of this worldwide disease

Rosetta FlexPepDock ab-initio: Simultaneous Folding, Docking and Refinement of Peptides onto Their Receptors

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions

Impact of corn processing and weaning age on calf performance, blood metabolites, rumen fermentation, and behavior

Abstract This study examined the impact of two corn processing methods (steam-flaked (SFC) vs. ground) combined with two weaning ages (50 or 75 days) on calf performance, blood metabolites, rumen fermentation, nutrient digestion, and behavior. The study involved 48 three-day-old Holstein calves, with an average body weight of 41.4 ± 2.2 kg. The experimental design was a 2 × 2 factorial arrangement, resulting in four treatment groups: SFC50 (SFC and weaning at 50 days), SFC75 (SFC and weaning at 75 days), GC50 (ground corn and weaning at 50 days), and GC75 (ground corn and weaning at 75 days). Calves were given whole milk at 4 L/ day from day 3–15 and 7 L/ day from day 16 to either 43 or 68, depending on weaning age. Weaning occurred between days 44 and 50 for early-weaned calves and between days 69 and 75 for late-weaned calves. The study lasted until calves were 93 days old. The starter ration consisted of soybean meal, corn grain, 5% chopped wheat straw and premix. Results indicated that the SFC-based starter feed improved calf performance and nutrient digestion, as evidenced by increased weight gain, dry matter, crude protein, and neutral detergent fiber digestibility. Calves fed the SFC-based starter diet had lower blood albumin and urea N concentrations, while blood total protein and globulin concentrations were higher, especially in early-weaned calves. No significant changes in rumen pH and ammonia-N concentration were observed. In addition, the SFC starter feed resulted in higher volatile fatty acids concentration and longer feeding time in weaned calves compared to ground corn. Overall, these results suggest that an SFC-based starter feed may be beneficial for both early and late weaned calves

Dressing down: convergent reduction of the mental disc in Garra (Teleostei: Cyprinidae) in the Middle East

In the Middle East, species of Garra are believed to have invaded the area in two independent waves from the Indo-Malayan biogeographic region. This hypothesis is based on the structure of the mental disc, a unique specialization of the lower lip, which is believed to be an adaptation to fast-flowing waters. While several species have such a mental disc, others completely lack a mental disc, being adapted to slow-moving water or to subterranean life. In this study, the phylogenetic relationships of Middle Eastern Garra species, including 16 described and 4 undescribed species, were analysed using mitochondrial cytochrome c oxidase I sequences. The results are concordant with traditional hypotheses on two invasion events; however, these invasion events are independent from the presence, absence or shape of the mental disc. We postulate convergent reduction of the mental disc in 5-6 independent lineages of Garra in the Middle East