55 research outputs found

    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

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    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

    Self-perceived stress reactivity is an indicator of psychosocial impairment at the workplace

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    BACKGROUND: Work related stress is associated with a range of debilitating health outcomes. However, no unanimously accepted assessment tool exists for the early identification of individuals suffering from chronic job stress. The psychological concept of self-perceived stress reactivity refers to the individual disposition of a person to answer stressors with immediate as well as long lasting stress reactions, and it could be a valid indicator of current as well as prospective adverse health outcomes. The aim of this study was to determine the extent to which perceived stress reactivity correlates with various parameters of psychosocial health, cardiovascular risk factors, and parameters of chronic stress and job stress in a sample of middle-aged industrial employees in a so-called "sandwich-position". METHODS: In this cross-sectional study, a total of 174 industrial employees were assessed for psychosocial and biological stress parameters. Differences between groups with high and low stress reactivity were analysed. Logistic regression models were applied to identify which parameters allow to predict perceived high versus low stress reactivity. RESULTS: In our sample various parameters of psychosocial stress like chronic stress and effort-reward imbalance were significantly increased in comparison to the normal population. Compared to employees with perceived low stress reactivity, those with perceived high stress reactivity showed poorer results in health-related complaints, depression, anxiety, sports behaviour, chronic stress, and effort-reward imbalance. The educational status of employees with perceived low stress reactivity is higher. Education, cardiovascular complaints, chronic stress, and effort-reward imbalance were moderate predictors for perceived stress reactivity. However, no relationship was found between stress reactivity and cardiovascular risk factors in our sample. CONCLUSIONS: Job stress is a major burden in a relevant subgroup of industrial employees in a middle management position. Self-perceived stress reactivity seems to be an appropriate concept to identify employees who experience psychosocial stress and associated psychological problems at the workplace

    The genome of the sea urchin Strongylocentrotus purpuratus

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    We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes

    The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5

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    One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels

    Social Relationships and Mortality Risk: A Meta-analytic Review

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    In a meta-analysis, Julianne Holt-Lunstad and colleagues find that individuals' social relationships have as much influence on mortality risk as other well-established risk factors for mortality, such as smoking

    A review of a quarter century of International Workshops on Seismic Anisotropy in the crust (0IWSA–12IWSA)

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