A2ML1 and otitis media: novel variants, differential expression, and relevant pathways

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media

Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton

Índice de seleção para escolha de populações segregantes de feijoeiro-comum Selection index for choosing segregating populations in common bean

Os objetivos deste trabalho foram determinar a viabilidade de uso de um índice de seleção baseado em somatório de variáveis padronizadas no melhoramento genético do feijoeiro-comum e identificar as populações segregantes mais promissoras em produtividade de grãos, porte da planta e resistência ao acamamento, simultaneamente. Foram avaliadas populações segregantes obtidas por cruzamentos em esquema de dialelo parcial (6x6). Os genitores utilizados foram divididos em dois grupos. No grupo I, foram utilizados genitores com grãos do tipo carioca, de porte semiereto a prostrado. No grupo II, foram utilizados genitores com porte ereto, porém com grãos fora do padrão comercial carioca. As gerações F2 e F3 das combinações híbridas foram avaliadas em experimentos com delineamento de blocos ao acaso, com três repetições e semeadura em novembro de 2007 e fevereiro de 2008, respectivamente. Os dados relativos à produtividade de grãos, à nota de porte e à nota de acamamento foram padronizados (Zij) por parcela. A partir do somatório de Zij, obteve-se o índice de seleção para as três características conjuntamente. Constatou-se que o índice de seleção possibilita selecionar populações segregantes superiores, considerando simultaneamente a produtividade de grãos e as notas de porte e de acamamento. As populações segregantes CV III 8511 x BRS 7762 Supremo, CV III 8511 x RP 166 e CV III 8511 x RP 26 são indicadas para programas de melhoramento a fim de obter linhagens produtivas com plantas eretas e menor acamamento.<br>The objectives of this work were to determine the viability of using a selection index based on the sum of standardized variables in common bean breeding programs, and to identify the most promising segregating populations for grain productivity, plant growth habit and resistance to lodging simultaneously. Segregant populations obtained by crosses in partial diallel scheme (6x6) were evaluated. Parental genotypes were divided in two groups. Group I comprised parents of the carioca grain type, with semierect to prostate growth habit. Group II comprised parental lines with erect architecture, but with grains not classified as the standard carioca type. The F2 and F3 generations of the obtained hybrid combinations were evaluated in randomized block design, with three replicates and sowing in November 2007 and February 2008, respectively. Data of grain yield, score for plant growth habit and score for lodging were standardized per plot (Zij). The selection index for the three characters together was obtained from the Zij sum. This selection index makes it possible to choose superior segregating populations considering grain yield, scores for plant growth habit, and for lodging simultaneously. Segregating populations CV III 8511 x BRS 7762 Supremo, CV III 8511 x RP 166 and CV III 8511 x RP 26 are identified as promising for breeding programs for grain productivity, plant architecture, and resistance to lodging, simultaneously