578 research outputs found
Bodyspace at the pub: sexual orientations and organizational space
In this article we argue that sexuality is not only an undercurrent of service environments, but is integral to the way that these workspaces are experienced and negotiated. Through drawing on Sara Ahmed’s (2006a) ‘orientation’ thesis, we develop a concept of ‘bodyspace’ to suggest that individuals understand, shape and make meaning of work spaces through complex sexually-orientated negotiations. Presenting analysis from a study of UK pubs, we explore bodyspace in the lived experience of workplace sexuality through three elements of orientation: background; bodily dwelling; and lines of directionality. Our findings show how organizational spaces afford or mitigate possibilities for particular bodies, which simultaneously shape expectations and experiences of sexuality at work. Bodyspace therefore provides one way of exposing the connection between sexual ‘orientation’ and the lived experience of service sector work
Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11
The ATP-dependent degradation of polyubiquitylated proteins by the 26S proteasome is essential for the maintenance of proteome stability and the regulation of a plethora of cellular processes. Degradation of substrates is preceded by the removal of polyubiquitin moieties through the isopeptidase activity of the subunit Rpn11. Here we describe three crystal structures of the heterodimer of the Mpr1-Pad1-N-terminal domains of Rpn8 and Rpn11, crystallized as a fusion protein in complex with a nanobody. This fusion protein exhibits modest deubiquitylation activity toward a model substrate. Full activation requires incorporation of Rpn11 into the 26S proteasome and is dependent on ATP hydrolysis, suggesting that substrate processing and polyubiquitin removal are coupled. Based on our structures, we propose that premature activation is prevented by the combined effects of low intrinsic ubiquitin affinity, an insertion segment acting as a physical barrier across the substrate access channel, and a conformationally unstable catalytic loop in Rpn11. The docking of the structure into the proteasome EM density revealed contacts of Rpn11 with ATPase subunits, which likely stabilize the active conformation and boost the affinity for the proximal ubiquitin moiety. The narrow space around the Rpn11 active site at the entrance to the ATPase ring pore is likely to prevent erroneous deubiquitylation of folded proteins
Allosteric modulation of the GTPase activity of a bacterial LRRK2 homolog by conformation-specific Nanobodies
Mutations in the Parkinson's disease (PD)-associated protein leucine-rich repeat kinase 2 (LRRK2) commonly lead to a reduction of GTPase activity and increase in kinase activity. Therefore, strategies for drug development have mainly been focusing on the design of LRRK2 kinase inhibitors. We recently showed that the central RocCOR domains (Roc: Ras of complex proteins; COR: C-terminal of Roc) of a bacterial LRRK2 homolog cycle between a dimeric and monomeric form concomitant with GTP binding and hydrolysis. PD-associated mutations can slow down GTP hydrolysis by stabilizing the protein in its dimeric form. Here, we report the identification of two Nanobodies (NbRoco1 and NbRoco2) that bind the bacterial Roco protein (CtRoco) in a conformation-specific way, with a preference for the GTP-bound state. NbRoco1 considerably increases the GTP turnover rate of CtRoco and reverts the decrease in GTPase activity caused by a PD-analogous mutation. We show that NbRoco1 exerts its effect by allosterically interfering with the CtRoco dimer–monomer cycle through the destabilization of the dimeric form. Hence, we provide the first proof of principle that allosteric modulation of the RocCOR dimer–monomer cycle can alter its GTPase activity, which might present a potential novel strategy to overcome the effect of LRRK2 PD mutations
The structure and functional roles of tidal flat meiobenthos
Meiofauna comprise the smallest multicellular and largest unicellular metazoans in benthic food webs. They are highly abundant and species-rich, yet essential aspects of the factors driving their community structure and abundance remain poorly understood. Similarly, their functional roles in benthic carbon cycling remain poorly characterized and even more poorly quantified. In the frame of two projects, we addressed questions regarding both the biotic and abiotic factors that drive meiobenthic assemblage structure, and their roles in benthic carbon cycling. Our research involved an intricate combination of manipulative laboratory experiments and field work, the latter mostly focusing on the intertidal flats bordering the Paulina salt marsh in the Scheldt estuary. The results add considerably to our understanding of the factors that drive meiobenthic assemblage structure. They clearly demonstrate that biotic interactions among different meiofauna, and between meio- and macrofauna, are extremely important and moderate the impacts of prominent abiotic drivers of assemblage structure such as granulometry and oxygen availability. From a functional point of view, we demonstrated that tidal flat meiofauna rely predominantly on carbon derived from in situ primary production by microphytobenthos. Quantification of grazing rates of meiofauna on microphytobenthos and benthic bacteria does not, however, point at an important direct contribution of meiofauna to benthic carbon cycling. The role of meiobenthic species diversity remains to be established, but laboratory experiments into the role of nematodes in OM decomposition reveal that in addition to species identity, species diversity does have a significant, yet largely unpredictable effect on OM decomposition rates
Triple intussusception involving heterotopic pancreatic tissue: a case report
<p>Abstract</p> <p>Introduction</p> <p>Intussusception involving heterotopic pancreatic tissue is a rare condition where a portion of the bowel telescopes into an adjacent segment with intraluminal pancreatic tissue as the lead point. Cases of heterotopic pancreas are most often described in the upper intestinal tract, particularly the stomach.</p> <p>Case presentation</p> <p>We present the case of a five-month-old boy of Caucasian ethnicity suffering acute abdominal pain and vomiting with an abdominal mass in the upper right quadrant. Work-up including ultrasound scan confirmed the intussusception. Repeated attempts at radiological reduction and two laparoscopic procedures were performed within 24 hours, which eventually led to the diagnosis of a triple intussusception.</p> <p>Conclusion</p> <p>To our knowledge, such a case of triple intussusception involving isolated heterotopic pancreatic tissue is previously unreported.</p
Agglomeration economies in the neighbourhood? Evidence from German cities
In urban renewal policy, it has become a widespread goal to revitalise neighbourhood economies. The rationale for these measures derives, to a great extent, from the concept of regional economic clusters, and, not surprisingly, one of their key objectives is to activate local inter-firm cooperation. This article examines the neighbourhood-related requirements and commitment of small firms. It draws on the results of a case study incorporating five German cities in which the neighbourhood-oriented applicability of economic policy was put to the test. As expected, it is unlikely for most small enterprises in urban renewal areas to engage in inter-firm cooperation focusing on the transfer of highly specialised knowledge. However, many small firms in inner city quarters appreciate neighbourhood characteristics as important location factors, and willingness to support local improvement efforts is relatively high, particularly among firms which operate successfully. The study suggests that there is a case for public policy to encourage small firms to participate in neighbourhood-based initiatives.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively
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