University College Cork

About: University College Cork is a education organization based out in Cork, Ireland. It is known for research contribution in the topics: Population & Irish. The organization has 12056 authors who have published 28452 publications receiving 958414 citations. The organization is also known as: Coláiste na hOllscoile Corcaigh & National University of Ireland, Cork.

A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease.

Abstract: Central core disease is a rare, nonprogressive myopathy that is characterized by hypotonia and proximal muscle weakness. In a large Mexican kindred with an unusually severe and highly penetrant form of the disorder, DNA sequencing identified an I4898T mutation in the C-terminal transmembrane/luminal region of the RyR1 protein that constitutes the skeletal muscle ryanodine receptor. All previously reported RYR1 mutations are located either in the cytoplasmic N terminus or in a central cytoplasmic region of the 5,038-aa protein. The I4898T mutation was introduced into a rabbit RYR1 cDNA and expressed in HEK-293 cells. The response of the mutant RyR1 Ca2+ channel to the agonists halothane and caffeine in a Ca2+ photometry assay was completely abolished. Coexpression of normal and mutant RYR1 cDNAs in a 1:1 ratio, however, produced RyR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca2+ release were reduced by 67%. [3H]Ryanodine binding indicated that the heterozygous channel is activated by Ca2+ concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells showed a significantly increased resting cytoplasmic Ca2+ level and a significantly reduced luminal Ca2+ level. These data are indicative of a leaky channel, possibly caused by a reduction in the Ca2+ concentration required for channel activation. Comparison with two other coexpressed mutant/normal channels suggests that the I4898T mutation produces one of the most abnormal RyR1 channels yet investigated, and this level of abnormality is reflected in the severe and penetrant phenotype of affected central core disease individuals.

Comparative genomics highlights the unique biology of Methanomassiliicoccales, a Thermoplasmatales-related seventh order of methanogenic archaea that encodes pyrrolysine

Abstract: A seventh order of methanogens, the Methanomassiliicoccales, has been identified in diverse anaerobic environments including the gastrointestinal tracts (GIT) of humans and other animals and may contribute significantly to methane emission and global warming Methanomassiliicoccales are phylogenetically distant from all other orders of methanogens and belong to a large evolutionary branch composed by lineages of non-methanogenic archaea such as Thermoplasmatales, the Deep Hydrothermal Vent Euryarchaeota-2 (DHVE-2, Aciduliprofundum boonei) and the Marine Group-II (MG-II) To better understand this new order and its relationship to other archaea, we manually curated and extensively compared the genome sequences of three Methanomassiliicoccales representatives derived from human GIT microbiota, “Candidatus Methanomethylophilus alvus", “Candidatus Methanomassiliicoccus intestinalis” and Methanomassiliicoccus luminyensis Comparative analyses revealed atypical features, such as the scattering of the ribosomal RNA genes in the genome and the absence of eukaryotic-like histone gene otherwise present in most of Euryarchaeota genomes Previously identified in Thermoplasmatales genomes, these features are presently extended to several completely sequenced genomes of this large evolutionary branch, including MG-II and DHVE2 The three Methanomassiliicoccales genomes share a unique composition of genes involved in energy conservation suggesting an original combination of two main energy conservation processes previously described in other methanogens They also display substantial differences with each other, such as their codon usage, the nature and origin of their CRISPRs systems and the genes possibly involved in particular environmental adaptations The genome of M luminyensis encodes several features to thrive in soil and sediment conditions suggesting its larger environmental distribution than GIT Conversely, “Ca M alvus” and “Ca M intestinalis” do not present these features and could be more restricted and specialized on GIT Prediction of the amber codon usage, either as a termination signal of translation or coding for pyrrolysine revealed contrasted patterns among the three genomes and suggests a different handling of the Pyl-encoding capacity This study represents the first insights into the genomic organization and metabolic traits of the seventh order of methanogens It suggests contrasted evolutionary history among the three analyzed Methanomassiliicoccales representatives and provides information on conserved characteristics among the overall methanogens and among Thermoplasmata

Psychosocial interventions for self‐harm in adults

Abstract: Background: Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and associated with suicide. This is an update of a broader Cochrane review first published in 1998, previously updated in 1999, and now split into three separate reviews. This review focuses on psychosocial interventions in adults who engage in self-harm. Objectives: To assess the effects of specific psychosocial treatments versus treatment as usual, enhanced usual care or other forms of psychological therapy, in adults following SH. Search methods: The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) trials coordinator searched the CCDAN Clinical Trials Register (to 29 April 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). Selection criteria: We included RCTs comparing psychosocial treatments with treatment as usual (TAU), enhanced usual care (EUC) or alternative treatments in adults with a recent (within six months) episode of SH resulting in presentation to clinical services. Data collection and analysis: We used Cochrane's standard methodological procedures.