Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss

Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSight^TM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.     

Divergent Toll-like receptors in catfish (Ictalurus punctatus): TLR5S, TLR20, TLR21

Toll-like receptors (TLR) mediate pathogen recognition in vertebrate species through detection of conserved microbial ligands. Families of TLR molecules have been described from the genomes of the teleost fish model species zebrafish and Takifugu, but much research remains to characterize the full length sequences and pathogen specificities of individual TLR members in fish. While the majority of these pathogen receptors are conserved among vertebrate species with clear orthologues present in fish for most mammalian TLRs, several interesting differences are present in the TLR repertoire of teleost fish when compared to that of mammals. A soluble form of TLR5 has been reported from salmonid fish and Takifugu rubripes which is not present in mammals, and a large group of TLRs (arbitrarily numbered 19-23) was identified from teleost genomes with no easily discernible orthologues in mammals. To better understand these teleost adaptations to the TLR family, we have isolated, sequenced, and characterized the full-length cDNA and gene sequences of TLR5S, TLR20, and TLR21 from catfish as well as studied their expression pattern in tissues. We also mapped these genes to bacterial artificial chromosome (BAC) clones for genome analysis. While TLR5S appeared to be common in teleost fish, and TLR21 is common to birds, amphibians and fish, TLR20 has only been identified in zebrafish and catfish. Phylogenetic analysis of catfish TLR20 indicated that it is closely related to murine TLR11 and TLR12, two divergent TLRs about which little is known. All three genes appear to exist in catfish as single copy genes.     

A BAC-based physical map of the channel catfish genome

Catfish is the major aquaculture species in the United States. To enhance its genome studies involving genetic linkage and comparative mapping, a bacterial artificial chromosome (BAC) contig-based physical map of the channel catfish (Ictalurus punctatus) genome was generated using four-color fluorescence-based fingerprints. Fingerprints of 34,580 BAC clones (5.6x genome coverage) were generated for the FPC assembly of the BAC contigs. A total of 3307 contigs were assembled using a cutoff value of 1x10(-20). Each contig contains an average of 9.25 clones with an average size of 292 kb. The combined contig size for all contigs was 0.965 Gb, approximately the genome size of the channel catfish. The reliability of the contig assembly was assessed by both hybridization of gene probes to BAC clones contained in the fingerprinted assembly and validation of randomly selected contigs using overgo probes designed from BAC end sequences. The presented physical map should greatly enhance genome research in the catfish, particularly aiding in the identification of genomic regions containing genes underlying important performance traits.     

Attention-dependent representation of a size illusion in human V1

One of the most fundamental properties of human primary visual cortex (V1) is its retinotopic organization, which makes it an ideal candidate for encoding spatial properties, such as size, of objects. However, three-dimensional (3D) contextual information can lead to size illusions that are reflected in the spatial pattern of activity in V1 [1]. A critical question is how complex 3D contextual information can influence spatial activity patterns in V1. Here, we assessed whether changes in the spatial distribution of activity in V1 depend on the focus of attention, which would be suggestive of feedback of 3D contextual information from higher visual areas. We presented two 3D rings at close and far apparent depths in a 3D scene. When subjects fixated its center, the far ring appeared to be larger and occupy a more eccentric portion of the visual field, relative to the close ring. Using functional magnetic resonance imaging, we found that the spatial distribution of V1 activity induced by the far ring was also shifted toward a more eccentric representation of the visual field, whereas that induced by the close ring was shifted toward the foveal representation, consistent with their perceptual appearances. This effect was significantly reduced when the focus of spatial attention was narrowed with a demanding central fixation task. We reason that focusing attention on the fixation task resulted in reduced activity in--and therefore reduced feedback from--higher visual areas that process the 3D depth cues.     

Achene anatomy and stomatal characteristics of eighteen Crepis L. (Asteraceae) taxa from Turkey with notes on their systematic significance

Achene anatomy and stomatal characteristics of eighteen Crepis taxa from Turkey are here described for the first time. In all taxa examined the pericarp is composed of several layers of sclerenchymatous and parenchymatous cells. As for the achene, differences among taxa mainly concern the pericarp structure and its thickness and width. Stomata are present on both surface of the leaf in all studied taxa and all taxa have anomocytic type stomata. However, the dimensions (length and width) and density of the stomata differ significantly among the studied taxa. In addition, the dimensions of stomata are negatively correlated with stomata density. It is concluded that achene anatomy and stomatal characteristics are useful for delimitation of Crepis taxa and a key to taxa based on these characters is provided. However, based on achene anatomy and stomatal characteristics, we found no argument for an exclusion of the Lagoseris group from Crepis as has previously been proposed.     

An Assessment of the Methodological Quality of Published Network Meta-Analyses: A Systematic Review

ObjectiveTo assess the methodological quality of published network meta-analysis.DesignSystematic review.MethodsWe searched the medical literature for network meta-analyses of pharmaceuticals. We assessed general study characteristics, study transparency and reproducibility, methodological approach, and reporting of findings. We compared studies published in journals with lower impact factors with those published in journals with higher impact factors, studies published prior to January 1^st, 2013 with those published after that date, and studies supported financially by industry with those supported by non-profit institutions or that received no support.ResultsThe systematic literature search identified 854 citations. Three hundred and eighteen studies met our inclusion criteria. The number of network meta-analyses has grown rapidly, with 48% of studies published since January 2013. The majority of network meta-analyses were supported by a non-profit institution or received no support (68%). We found considerable inconsistencies among reviewed studies. Eighty percent reported search terms, 61% a network diagram, 65% sufficient data to replicate the analysis, and 90% the characteristics of included trials. Seventy percent performed a risk of bias assessment of included trials, 40% an assessment of model fit, and 56% a sensitivity analysis. Among studies with a closed loop, 69% examined the consistency of direct and indirect evidence. Sixty-four percent of studies presented the full matrix of head-to-head treatment comparisons. For Bayesian studies, 41% reported the probability that each treatment was best, 31% reported treatment ranking, and 16% included the model code or referenced publicly-available code. Network meta-analyses published in higher impact factors journals and those that did not receive industry support performed better across the assessment criteria. We found few differences between older and newer studies.ConclusionsThere is substantial variation in the network meta-analysis literature. Consensus among guidelines is needed improve the methodological quality, transparency, and consistency of study conduct and reporting.     

Are synthetic biology standards applicable in everyday research practice?

The issue of standardization in synthetic biology is a recurring one. As a discipline that incorporates engineering principles into biological designs, synthetic biology needs effective ways to communicate results and allow different researchers (both academic and industrial) to build upon previous results and improve on existing designs. An aspect that is left out of the discussions, especially when they happen at the level of academic and industrial consortia or policymaking, is whether or not standards are applicable or even useful in everyday research practice. In this caucus article, we examine this particular issue with the hope of including it in the standardization discussions agenda and provide insights into a topic that synthetic biology researchers experience daily.