A Myo6 Mutation Destroys Coordination between the Myosin Heads, Revealing New Functions of Myosin VI in the Stereocilia of Mammalian Inner Ear Hair Cells

Myosin VI, found in organisms from Caenorhabditis elegans to humans, is essential for auditory and vestibular function in mammals, since genetic mutations lead to hearing impairment and vestibular dysfunction in both humans and mice. Here, we show that a missense mutation in this molecular motor in an ENU-generated mouse model, Tailchaser, disrupts myosin VI function. Structural changes in the Tailchaser hair bundles include mislocalization of the kinocilia and branching of stereocilia. Transfection of GFP-labeled myosin VI into epithelial cells and delivery of endocytic vesicles to the early endosome revealed that the mutant phenotype displays disrupted motor function. The actin-activated ATPase rates measured for the D179Y mutation are decreased, and indicate loss of coordination of the myosin VI heads or ‘gating’ in the dimer form. Proper coordination is required for walking processively along, or anchoring to, actin filaments, and is apparently destroyed by the proximity of the mutation to the nucleotide-binding pocket. This loss of myosin VI function may not allow myosin VI to transport its cargoes appropriately at the base and within the stereocilia, or to anchor the membrane of stereocilia to actin filaments via its cargos, both of which lead to structural changes in the stereocilia of myosin VI–impaired hair cells, and ultimately leading to deafness

Sex- and Diet-Specific Changes of Imprinted Gene Expression and DNA Methylation in Mouse Placenta under a High-Fat Diet

Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable

How should laboratories communicate with primary care? Obtaining general practitioners' views.

AIMS: Recognising the importance of communication with our primary care colleagues, focus groups were held with GPs to determine how they perceived the current lines of communication with their local microbiology laboratory and the PHLS, and how they could be improved. METHODS: Focus groups were held in Plymouth, Gloucester, Bristol and Hereford. Between four and 10 GPs and/or PCG Board members attended each workshop. The modes of communication i.e. websites, face-to-face contact, laboratory reporting, telephone advice, newsletters, guidance and surveillance were discussed. RESULTS: Microbiology websites should be user friendly, with clear labelling as to whom the page is directed. They should contain locally relevant data, antibiotic guidance and information leaflets. Despite great variation in laboratory reporting protocols GPs were mostly happy with reports received. Results, especially serology, should contain a clear conclusion and could refer to a website for further information. Electronic reporting was enthusiastically awaited. All GPs felt they had excellent access to telephone advice. GPs would value data and guidance on their use of diagnostic tests. CONCLUSION: These workshops highlight the variation in laboratory reporting protocols that should be addressed. Website development for GPs should include locally relevant data. GPs would value details of their laboratory use and costs

Photochemistry of Transition Metal Complexes Induced by Outer-Sphere Charge Transfer Excitation

The intermolecular (outer sphere, OS) interaction of a reducing and an oxidizing metal complex generates a new optical transition involving charge transfer (CT) from the electron donor to the acceptor. OS CT transitions are classified according to the redox site (metal or ligand). Generally, the interaction between donor and acceptor is facilitated by ion pairs consisting of an oxidizing complex cation and a reducing complex anion. There are also ion pairs which are composed of a metal complex and an organic counter ion as electron donor or acceptor. In addition, the review includes examples of OS CT interaction which do not involve ion pairs at all. — A short introduction into the theory is followed by the discussion of the spectroscopy of OS CT of transition metal complexes. Finally, photoreactions induced by OS CT transitions are reviewed. The optical transfer is frequently followed by a rapid back electron transfer which regenerates the starting complexes. In many cases the primary products are kinetically labile and substitution reactions compete successfully with back electron transfer. As a result stable redox products may be formed. As an alternative, the substitution can be followed by back electron transfer. Product formation appears then as a substitution of the starting complexes. The various possibilities are illustrated by appropriate examples

Ciência & Saúde Coletiva: análise da produção científica e redes colaborativas de pesquisa

The purpose of this metric and descriptive study was to identify the most productive authors and their collaborative research networks from articles published in Ciência & Saúde Coletiva between, 2005, and 2014. Authors meeting the cutoff criteria of at least 10 articles were considered the most productive authors. VOSviewer and Network Workbench technologies were applied for visual representations of collaborative research networks involving the most productive authors in the period. Initial analysis recovered 2511 distinct articles, with 8920 total authors with an average of 3.55 authors per article. Author analysis revealed 6288 distinct authors, 24 of these authors were identified as the most productive. These 24 authors generated 287 articles with an average of 4.31 authors per article, and represented 8 separate collaborative partnerships, the largest of which had 14 authors, indicating a significant degree of collaboration among these authors. This analysis provides a visual representation of networks of knowledge development in public health and demonstrates the usefulness of VOSviewer and Network Workbench technologies in future research