The Mre11 complex (Mre11 Rad50 Nbs1) is central to chromosomal maintenance and functions in homologous recombination, telomere maintenance and sister chromatid association. These functions all imply that the linked binding of two DNA substrates occurs, although the molecular basis for this process remains unknown. Here we present a 2.2 A crystal structure of the Rad50 coiled-coil region that reveals an unexpected dimer interface at the apex of the coiled coils in which pairs of conserved Cys-X-X-Cys motifs form interlocking hooks that bind one Zn(2+) ion. Biochemical, X-ray and electron microscopy data indicate that these hooks can join oppositely protruding Rad50 coiled-coil domains to form a flexible bridge of up to 1,200 A. This suggests a function for the long insertion in the Rad50 ABC-ATPase domain. The Rad50 hook is functional, because mutations in this motif confer radiation sensitivity in yeast and disrupt binding at the distant Mre11 nuclease interface. These data support an architectural role for the Rad50 coiled coils in forming metal-mediated bridging complexes between two DNA-binding heads. The resulting assemblies have appropriate lengths and conformational properties to link sister chromatids in homologous recombination and DNA ends in non-homologous end-joining.
BackgroundMany workplaces have implemented sit-stand workstations (SSW), which enable a worker to transition between sitting and standing as they perform their work activities. The factors which determine the initial adoption, sustainability or cessation of use for a SSW, remain largely unexamined. This study investigates the experiences of workers who had previously used or were currently using a SSW.MethodsThe study setting was within an Australian university. Participants who were current or past SSW users, as well as workplace key informants, were interviewed for the study. All interviews were recorded, transcribed and analysed. Transcripts were coded by two researchers for concepts and themes regarding uptake and sustainability of SSW. Discussion and validation of themes was undertaken by the team of three researchers.ResultsA total of 24 interviews were conducted. Twenty-two interviews were with ceased and current users (16 current and six ceased users) and two interviews were with workplace key informants. Analysis of the interviews with current and ceased users identified three main themes: Personal considerations for use/sustainability; Posture; and Usability. Analysis of the interviews with key informants identified two themes: Considerations and concerns and Policies and procedures. Little information was provided to workers when first using a SSW. Workers who were able to adopt their working style to the new workstations were able to sustain ongoing use of a SSW. Key informants were concerned that employees believed using a SSW would provide a health benefit in its own right without an understanding of the possible risks that might be associated with use.ConclusionsSustainable usage of this type of SSW is achievable, however, it requires some element of adaptation at the individual worker level. Participants spoke about how the use of the SSW in a standing position was typically associated with the time of day, specific task selection and musculoskeletal comfort or fatigue factors. The provision of education to new SSW users with relevant supporting information by a subject matter expert should enable the worker to obtain a more holistic understanding of the safety and health risks and benefits embedded in the use of a SSW.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-6296-6) contains supplementary material, which is available to authorized users.
The introduction of post-prevention control however proven to be effective with workers' fatigue and emotional exhaustion instead of working condition of this companies. This study contributes to aircraft ground handling safety by investigating the workers' fatigue factors, thus helping to improve the company and individual performance as well as reduce the risks related to fatigue.
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