Usher Syndrome in the Inner Ear: Etiologies and Advances in Gene Therapy

Hearing loss is the most common sensory disorder with ~466 million people worldwide affected, representing about 5% of the population. A substantial portion of hearing loss is genetic. Hearing loss can either be non-syndromic, if hearing loss is the only clinical manifestation, or syndromic, if the hearing loss is accompanied by a collage of other clinical manifestations. Usher syndrome is a syndromic form of genetic hearing loss that is accompanied by impaired vision associated with retinitis pigmentosa and, in many cases, vestibular dysfunction. It is the most common cause of deaf-blindness. Currently cochlear implantation or hearing aids are the only treatments for Usher-related hearing loss. However, gene therapy has shown promise in treating Usher-related retinitis pigmentosa. Here we review how the etiologies of Usher-related hearing loss make it a good candidate for gene therapy and discuss how various forms of gene therapy could be applied to Usher-related hearing loss.     

Intelligence and Leadership: A Quantitative Review and Test of Theoretical Propositions.

Meta-analysis was used to aggregate results from studies examining the relationship between intelligence and leadership. One hundred fifty-one independent samples in 96 sources met the criteria for inclusion in the meta-analysis. Results indicated that the corrected correlation between intelligence and leadership is .21 (uncorrected for range restriction) and .27 (corrected for range restriction). Perceptual measures of intelligence showed stronger correlations with leadership than did paper-and-pencil measures of intelligence. Intelligence correlated equally well with objective and perceptual measures of leadership. Additionally, the leader's stress level and the leader's directiveness moderated the intelligence-leadership relationship. Overall, results suggest that the relationship between intelligence and leadership is considerably lower than previously thought. The results also provide meta-analytic support for both implicit leadership theory and cognitive resource theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Architecture of protein and DNA contacts within the TFIIIB-DNA complex

The RNA polymerase III factor TFIIIB forms a stable complex with DNA and can promote multiple rounds of initiation by polymerase. TFIIIB is composed of three subunits, the TATA binding protein (TBP), TFIIB-related factor (BRF), and B". Chemical footprinting, as well as mutagenesis of TBP, BRF, and promoter DNA, was used to probe the architecture of TFIIIB subunits bound to DNA. BRF bound to TBP-DNA through the nonconserved C-terminal region and required 15 bp downstream of the TATA box and as little as 1 bp upstream of the TATA box for stable complex formation. In contrast, formation of complete TFIIIB complexes required 15 bp both upstream and downstream of the TATA box. Hydroxyl radical footprinting of TFIIIB complexes and modeling the results to the TBP-DNA structure suggest that BRF and B" surround TBP on both faces of the TBP-DNA complex and provide an explanation for the exceptional stability of this complex. Competition for binding to TBP by BRF and either TFIIB or TFIIA suggests that BRF binds on the opposite face of the TBP-DNA complex from TFIIB and that the binding sites for TFIIA and BRF overlap. The positions of TBP mutations which are defective in binding BRF suggest that BRF binds to the top and N-terminal leg of TBP. One mutation on the N-terminal leg of TBP specifically affects the binding of the B" subunit.     

OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans

Although cyclic nucleotide-gated channels mediate sensory transduction in olfaction and vision, other forms of sensory transduction are independent of these channels. Caenorhabditis elegans cyclic nucleotide-gated channel mutants respond normally to some olfactory stimuli and to osmotic stimuli, suggesting that these chemosensory responses use an alternative sensory transduction pathway. One gene that may act in this pathway is osm-9, which is required for each of these responses as well as a mechanosensory response to nose touch. osm-9 encodes a protein with ankyrin repeats and multiple predicted transmembrane domains that has limited similarity to the Drosophila phototransduction channels transient receptor potential (TRP) and TRP-like (TRPL). The sequence of OSM-9 and other TRP-like genes reveals a previously unsuspected diversity of mammalian and invertebrate genes in this family. osm-9 is required for the activity of the predicted G-protein-coupled odorant receptor ODR-10, which acts in the AWA olfactory neurons; its similarity to other G-protein-regulated transduction channels suggests that OSM-9 is involved in AWA signaling. osm-9:: GFP fusion genes are expressed in a subset of chemosensory, mechanosensory, and osmosensory neurons. osm-9 also affects olfactory adaptation within neurons that require the cyclic nucleotide-gated channel for olfaction; in these neurons, the gene has a regulatory function and not a primary role in sensory transduction.     

The biological function of Pavlovian conditioning: A mechanism for mating success in the blue gourami (Trichogaster trichopterus).

Reproductive behavior can be elicited by signals that animals learn to associate with mates during repeated sexual encounters. Although researchers frequently have speculated about the evolutionary function of this Pavlovian-conditioned behavior, experimental evidence has been sparse. An experiment with blue gourami fish (Trichogaster trichopterus) demonstrates that both males and females learn to anticipate mates and that signaling enables territorial males to inhibit their characteristic initial aggressive response to females. Pavlovian-conditioned males exhibited more courtship appeasement behavior and less aggression than males whose contact with females was unsignaled. These data suggest that in nature Pavlovian conditioning can play an important role in the reproductive behavior of territorial species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distribution of 7Be, 210Pb and 137Cs in watersheds of different scales in the Seine River basin: inventories and residence times

The activity of environmental radionuclides ((7)Be, (210)Pb and (137)Cs) was monitored in nested catchments, inside the Seine River basin. Suspended matter data was collected at 8 different watersheds, ranging from order 1 to order 7, and ranging in size over 4 orders of magnitude. Suspended matter was analyzed for (210)Pb, (137)Cs and (7)Be, and used to calculate the flux of sediments out of each watershed. Monthly atmospheric flux data of (210)Pb and (7)Be was analyzed to assess the input flux of each into the watersheds, taking into account the rainfall during sampling periods. Taking advantage of the different half-lives of (7)Be (53 days) and (210)Pb (22 years), a two-box model was built for each of the catchments following a methodology previously developed by Dominik et al. [Dominik J, Burrus D, Vernet JP. Transport of the environmental radionuclides in alpine watershed. Earth Planet Sci Letters 1987; 84: 165-180.]. The model divides the watershed into a soil box and a rapid reservoir and provides insight into the removal rate of suspended matter from the surrounding watershed. The model enables the assessment of the surface area and the residence time of slow and rapid reservoirs to describe the fate of contaminants of atmospheric origin inside the river basin. The model was improved by considering the dissolved fraction in the total flux and adding the (137)Cs inventory as an additional constraint. The effects of these changes are discussed. Residence times in the soil box, characterized by low transport velocity, range between 4800 years at Melarchez (order 1) to about 30000 years at Andresy and Poses (order 7). They remain constant in each watershed over a large range of variation of atmospheric fluxes of (7)Be and (210)Pb during the whole study, but are sensitive to SM variations. The residence time in the rapid box, which includes the surface of the river and immediate surroundings, is less than one year, while its surface area is in the range 0.6% to 2.2% of the total catchment area. They are sensitive to (7)Be atmospheric flux variations. The two-box model was used to estimate the amount of the radionuclides in each reservoir. Inventories appear to be constant from one watershed to the next. The (7)Be inventory ratio in the rapid and slow boxes expresses the rate of particle-reactive atmospheric pollutants that will be rapidly delivered to the river.