133 research outputs found

    Gene regulatory factors of the sea urchin embryo. II. Two dissimilar proteins, P3A1 and P3A2, bind to the same target sites that are required for early territorial gene expression

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    Previous work demonstrated that a negative regulatory interaction mediated by factor(s) termed 'P3A' is required for correct territory-specific gene expression in the sea urchin embryo. A probe derived from a P3A target site in the skeletogenic SM50 gene of Strongylocentrotus purpuratus was used to isolate a cDNA clone coding for a factor that binds specifically to this site. This factor, called P3A1, contains two sequence elements that belong to the Zn finger class of DNA-binding motifs, and in these regions is most closely similar to the Drosophila hunchback factor. The P3A1 factor also binds to a similar target sequence in a second gene, CyIIIa, expressed in embryonic aboral ectoderm. Another sea urchin embryo protein factor, P3A2, has been isolated by affinity chromatography and cloned, as described in Calzone et al. Development 112, 335-350 (1991). P3A2 footprints the same target sites in the SM50 and CyIIIa genes as does P3A1, but lacks the Zn finger sequence motifs and in amino acid sequence is almost entirely dissimilar to P3A1. A deletion analysis of P3A2 delimited the DNA-binding region, revealing that five specific amino acids in the first P3A1 finger region and four in the second P3A1 finger region are also present in equivalent positions in P3A2. The P3A1 and P3A2 factors could function as regulatory antagonists, having evolved similar target specificities from dissimilar DNA-binding domains

    Synaptonemal Complex Components Persist at Centromeres and Are Required for Homologous Centromere Pairing in Mouse Spermatocytes

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    Recent studies in simple model organisms have shown that centromere pairing is important for ensuring high-fidelity meiotic chromosome segregation. However, this process and the mechanisms regulating it in higher eukaryotes are unknown. Here we present the first detailed study of meiotic centromere pairing in mouse spermatogenesis and link it with key events of the G2/metaphase I transition. In mouse we observed no evidence of the persistent coupling of centromeres that has been observed in several model organisms. We do however find that telomeres associate in non-homologous pairs or small groups in B type spermatogonia and pre-leptotene spermatocytes, and this association is disrupted by deletion of the synaptonemal complex component SYCP3. Intriguingly, we found that, in mid prophase, chromosome synapsis is not initiated at centromeres, and centromeric regions are the last to pair in the zygotene-pachytene transition. In late prophase, we first identified the proteins that reside at paired centromeres. We found that components of the central and lateral element and transverse filaments of the synaptonemal complex are retained at paired centromeres after disassembly of the synaptonemal complex along diplotene chromosome arms. The absence of SYCP1 prevents centromere pairing in knockout mouse spermatocytes. The localization dynamics of SYCP1 and SYCP3 suggest that they play different roles in promoting homologous centromere pairing. SYCP1 remains only at paired centromeres coincident with the time at which some kinetochore proteins begin loading at centromeres, consistent with a role in assembly of meiosis-specific kinetochores. After removal of SYCP1 from centromeres, SYCP3 then accumulates at paired centromeres where it may promote bi-orientation of homologous centromeres. We propose that, in addition to their roles as synaptonemal complex components, SYCP1 and SYCP3 act at the centromeres to promote the establishment and/or maintenance of centromere pairing and, by doing so, improve the segregation fidelity of mammalian meiotic chromosomes

    Burnout, working conditions and gender— results from the northern SwedenMONICAStudy,”BMCPublic Health,

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    Abstract Background: Sick-leave because of mental and behavioural disorders has increased considerably in Sweden since the late nineties, and especially in women. The aim of this study was to assess the level of burnout in the general working population in northern Sweden and analyse it's relation to working conditions and gender. Methods: In this cross-sectional study the survey from the MONICA-study (Monitoring of Trends and Determinants in Cardiovascular Disease) in northern Sweden 2004 was used. A burnout instrument, the Shirom Melamed Burnout Questionnaire (SMBQ), was incorporated in the original survey which was sent to a random sample of 2500 individuals with a response rate of 76%. After including only actively working people, aged 25-64 years, our study population consisted of 1000 participants (497 women and 503 men). ANOVA and multiple linear regression models were used. Results: The prevalence of a high level of burnout (SMBQ >4.0) was 13%. Women had a higher level of burnout than men with the most pronounced difference in the age group 35-44 years. In both sexes the level of burnout decreased with age. Demand and control at work, and job insecurity were related to burnout. In women the level of education, socioeconomic position, work object, and working varying hours were of importance. Interaction effects were found between sex and work object, and sex and working hours. In a multiple regression analysis almost half of the gender difference could be explained by work related and life situational factors. Conclusions: Working life conditions contributed to the level of burnout in this actively working sample from the general population in northern Sweden. Especially in women, socioeconomic position was associated with burnout. The high level of burnout in women compared to men was partly explained by more unfavourable working conditions and life situational factors. Efforts to level out gender differences in burnout should probably focus on improving both working and socioeconomic conditions for women

    Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens

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    NMR structures of the glutaredoxin (GLXR) domains from Br. melitensis and Ba. henselae have been determined as part of the SSGCID initiative. Comparison of the domains with known structures reveals overall structural similarity between these proteins and previously determined E. coli GLXR structures, with minor changes associated with the position of helix 1 and with regions that diverge from similar structures found in the closest related human homolog

    Ignicoccus hospitalis and Nanoarchaeum equitans: ultrastructure, cell–cell interaction, and 3D reconstruction from serial sections of freeze-substituted cells and by electron cryotomography

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    Ultrastructure and intercellular interaction of Ignicoccus hospitalis and Nanoarchaeum equitans were investigated using two different electron microscopy approaches, by three-dimensional reconstructions from serial sections, and by electron cryotomography. Serial sections were assembled into 3D reconstructions, for visualizing the unusual complexity of I. hospitalis, its huge periplasmic space, the vesiculating cytoplasmic membrane, and the outer membrane. The cytoplasm contains fibres which are reminiscent to a cytoskeleton. Cell division in I. hospitalis is complex, and different to that in Euryarchaeota or Bacteria. An irregular invagination of the cytoplasmic membrane is followed by separation of the two cytoplasms. Simultaneous constriction of cytoplasmic plus outer membrane is not observed. Cells of N. equitans show a classical mode of cell division, by constriction in the mid-plane. Their cytoplasm exhibits two types of fibres, elongated and ring-shaped. Electron micrographs of contact sites between I. hospitalis and N. equitans exhibit two modes of interaction. One is indirect and mediated by thin fibres; in other cells the two cell surfaces are in direct contact. The two membranes of I. hospitalis cells are frequently seen in direct contact, possibly a prerequisite for transporting metabolites or substrates from the cytoplasm of one cell to the other. Rarely, a transport based on cargo vesicles is observed between I. hospitalis and N. equitans
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