Structural organization of gap junction channels

AbstractGap junctions were initially described morphologically, and identified as semi-crystalline arrays of channels linking two cells. This suggested that they may represent an amenable target for electron and X-ray crystallographic studies in much the same way that bacteriorhodopsin has. Over 30 years later, however, an atomic resolution structural solution of these unique intercellular pores is still lacking due to many challenges faced in obtaining high expression levels and purification of these structures. A variety of microscopic techniques, as well as NMR structure determination of fragments of the protein, have now provided clearer and correlated views of how these structures are assembled and function as intercellular conduits. As a complement to these structural approaches, a variety of mutagenic studies linking structure and function have now allowed molecular details to be superimposed on these lower resolution structures, so that a clearer image of pore architecture and its modes of regulation are beginning to emerge

The Mr 28,000 gap junction proteins from rat heart and liver are different but related

The sequence of the amino-terminal 32 residues of the rat heart Mr 28,000 gap junction protein presented here allows, for the first time, a sequence comparison of gap junctional proteins from different tissues (heart and liver). Comparison of the rat heart gap junction protein sequence and that available from rat liver reveals 43% sequence identity and conservative changes at an additional 25% of the positions. Both proteins exhibit a hydrophobic domain which could represent a transmembrane span of the junction. This result unequivocally demonstrates the existence of at least two forms of the gap junction protein. As yet, no homology is evident between the gap junctional proteins of either heart or liver and main intrinsic protein from rat eye lens

Interactions between innexins UNC-7 and UNC-9 mediate electrical synapse specificity in the Caenorhabditis elegans locomotory nervous system

<p>Abstract</p> <p>Background</p> <p>Approximately 10% of <it>Caenorhabditis elegans </it>nervous system synapses are electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes <it>unc-7 </it>and <it>unc-9 </it>result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to electrical synapse connectivity.</p> <p>Results</p> <p><it>unc-7 </it>encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In <it>Xenopus </it>oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. <it>Xenopus </it>oocyte studies and co-localization studies in <it>C. elegans </it>suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic.</p> <p>Conclusion</p> <p>UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for electrical synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in <it>C. elegans</it>, and other factors must influence the determination of synaptic partners.</p

Some reactions of azides with diynyl-bis(phosphine)ruthenium-cyclopentadienyl complexes

Abstract not availableMichael I. Bruce, Alexandre Burgun, Jonathan George, Brian K. Nicholson, Christian R. Parker, Brian W. Skelton, Nancy Scoleri, Christopher J. Sumby, Natasha N. Zaitsev

Occupational therapy consensus recommendations for functional neurological disorder

BACKGROUND: People with functional neurological disorder (FND) are commonly seen by occupational therapists; however, there are limited descriptions in the literature about the type of interventions that are likely to be helpful. This document aims to address this issue by providing consensus recommendations for occupational therapy assessment and intervention. METHODS: The recommendations were developed in four stages. Stage 1: an invitation was sent to occupational therapists with expertise in FND in different countries to complete two surveys exploring their opinions regarding best practice for assessment and interventions for FND. Stage 2: a face-to-face meeting of multidisciplinary clinical experts in FND discussed and debated the data from stage 1, aiming to achieve consensus on each issue. Stage 3: recommendations based on the meeting were drafted. Stage 4: successive drafts of recommendations were circulated among the multidisciplinary group until consensus was achieved. RESULTS: We recommend that occupational therapy treatment for FND is based on a biopsychosocial aetiological framework. Education, rehabilitation within functional activity and the use of taught self-management strategies are central to occupational therapy intervention for FND. Several aspects of occupational therapy for FND are distinct from therapy for other neurological conditions. Examples to illustrate the recommendations are included within this document. CONCLUSIONS: Occupational therapists have an integral role in the multidisciplinary management of people with FND. This document forms a starting point for research aiming to develop evidence-based occupational therapy interventions for people with FND

Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12–15 Months

Background: M-M-RTMII (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (PriorixTM, GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States. Methods: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12–15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis Avaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed. Results: Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3–99.2% (measles), 89.7–90.7% (mumps), and 97.5–98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3MMR-RITlotsorMMRII.T here were no apparent differences in solicited or serious adverse events among the 4 groups. Conclusions: Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7. Clinical Trials Registration. NCT00861744; etrack; 11187

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

Interstellar Turbulence II: Implications and Effects

Interstellar turbulence has implications for the dispersal and mixing of the elements, cloud chemistry, cosmic ray scattering, and radio wave propagation through the ionized medium. This review discusses the observations and theory of these effects. Metallicity fluctuations are summarized, and the theory of turbulent transport of passive tracers is reviewed. Modeling methods, turbulent concentration of dust grains, and the turbulent washout of radial abundance gradients are discussed. Interstellar chemistry is affected by turbulent transport of various species between environments with different physical properties and by turbulent heating in shocks, vortical dissipation regions, and local regions of enhanced ambipolar diffusion. Cosmic rays are scattered and accelerated in turbulent magnetic waves and shocks, and they generate turbulence on the scale of their gyroradii. Radio wave scintillation is an important diagnostic for small scale turbulence in the ionized medium, giving information about the power spectrum and amplitude of fluctuations. The theory of diffraction and refraction is reviewed, as are the main observations and scintillation regions.Comment: 46 pages, 2 figures, submitted to Annual Reviews of Astronomy and Astrophysic