How) do work placements work: scrutinising the quantitative evidence for a theory-driven future research agenda

While supervised work placements are increasingly popular in higher education, evidence regarding their effects on career outcomes remain somewhat sparse and atheoretical. The aim of this systematic literature review is to evaluate the effectiveness of placements for career outcomes and to identify any underpinning core psychological processes and to offer a theoretically grounded framework for future research. Drawing on transition theory (Schlossberg, 1981) and career construction theory (Savickas, 1997), we argue that supervised work experiences are central transition experiences that enable social learning processes and trigger changes in a person’s identity development as a professional, thereby increasing career resources and employability which in turn affect future career outcomes positively. We screened 2,394 systematically selected abstracts across several databases and disciplines. Only quantitative studies that either offered a control-group or a longitudinal design were included, resulting in an in-depth review of 40 studies, applying a rigorous evaluation protocol. Placement participation elicits an overall positive (but small) effect on career outcomes: Graduates who completed a work placement found employment more quickly. Work placements also changed students’ perceptions of self-efficacy, their knowledge, skills, and attitudes. We suggest that these changes could be seen as indicative of the proposed social learning processes and identity changes that positively affect career resources. Our review points to several gaps in the literature, and building on existing career theories, we develop a theoretical model and offer new avenues for future research to integrate the heterogenic field of placement research and inform career research in other areas

Megadalton-sized dityrosine aggregates of α-synuclein retain high degrees of structural disorder and internal dynamics

Heterogeneous aggregates of the human protein α-synuclein (αSyn) are abundantly found in Lewy body inclusions of Parkinson’s disease patients. While structural information on classical αSyn amyloid fibrils is available, little is known about the conformational properties of disease-relevant, non-canonical aggregates. Here, we analyze the structural and dynamic properties of megadalton-sized dityrosine adducts of αSyn that form in the presence of reactive oxygen species and cytochrome c, a proapoptotic peroxidase that is released from mitochondria during sustained oxidative stress. In contrast to canonical cross-β amyloids, these aggregates retain high degrees of internal dynamics, which enables their characterization by solution-state NMR spectroscopy. We find that intermolecular dityrosine crosslinks restrict αSyn motions only locally whereas large segments of concatenated molecules remain flexible and disordered. Indistinguishable aggregates form in crowded in vitro solutions and in complex environments of mammalian cell lysates, where relative amounts of free reactive oxygen species rather than cytochrome c are rate limiting. We further establish that dityrosine adducts inhibit classical amyloid formation by maintaining αSyn in its monomeric form and that they are non-cytotoxic despite retaining basic membrane-binding properties. Our results suggest that oxidative αSyn aggregation scavenges cytochrome c’s activity into the formation of amorphous, high molecular-weight structures that may contribute to aggregate diversity in Lewy body deposits

On the dynamics of work identity in atypical employment: setting out a research agenda

Starting from the notion that work is an important part of who we are, we extend existing theory making on the interplay of work and identity by applying them to (so called) atypical work situations. Without the contextual stability of a permanent organizational position, the question “who one is” will be more difficult to answer. At the same time, a stable occupational identity might provide an even more important orientation to one’s career attitudes and goals in atypical employment situations. So, although atypical employment might pose different challenges on identity, identity can still be a valid concept to assist the understanding of behaviour, attitudes, and well-being in these situations. Our analysis does not attempt to “reinvent” the concept of identity, but will elaborate how existing conceptualizations of identity as being a multiple (albeit perceived as singular), fluid (albeit perceived as stable), and actively forged (as well as passively influenced) construct that can be adapted to understand the effects of atypical employment contexts. Furthermore, we suggest three specific ways to understand the longitudinal dynamics of the interplay between atypical employment and identity over time: passive incremental, active incremental, and transformative change. We conclude with key learning points and outline a few practical recommendations for more research into identity as an explanatory mechanism for the effects of atypical employment situations

Understanding the Relationship Between Job Insecurity and Performance: Hindrance or Challenge Effect?

This study aims to propose a theoretical model that explains the psychological processes underlying the job insecurity-performance relationship. To accomplish this goal, we draw on a two-dimensional stressor framework. Job insecurity may undermine performance through a hindrance effect, because it causes strain reactions and withdrawal behaviours. In contrast, it can trigger productive behaviours as a form of job preservation strategy, when reacting actively. These competing predictions are integrated in the same structural equation modeling by testing the negative indirect effect of job insecurity on task and contextual performance, mediated by job satisfaction and affective commitment. The positive challenge effect is examined by testing the remaining direct path to performance. To provide convergence of evidence, two studies were conducted with the purpose to replicate patters and findings across different measures and samples. The results provide support only for negative and passive reactions to job insecurity, leading to lower performance

Bcl-2 expression in rituximab refractory cutaneous B-cell lymphoma

Rituximab has been established as an effective and safe therapy for cutaneous B-cell lymphoma (CBCL). Different survival pathways, that is the Raf/MEK/Erk- or the p38MAPK cascade, have been suggested as downstream mediators of rituximab and may be involved in treatment failure. Biopsies from four patients, suffering from different subtypes of CBCL, which were obtained at various time points of relapse during or after therapy with 375 mg rituximab per m2 of body surface area, were analysed for the expression of CD20, CD3, Ki-67, Raf-kinase inhibitory protein (RKIP) and bcl-2 by immunohistochemistry. No CD20-loss variants, that is the suggested main tumour escape mechanism to rituximab therapy, were observed in any specimen of relapsing CBCL. Notably, the expression of proapoptotic RKIP remained increased in these tumour samples. This was concomitated by a constant to slightly reduced proliferation status as demonstrated by Ki-67 staining. However, relapsing CBCL exhibited a strong upregulation of the antiapoptotic molecule bcl-2 in comparison to pretherapeutic levels. The immunohistochemical analyses of this case series of rituximab refractory CBCL suggest that upregulation of bcl-2 may play a major role in therapy resistance

In-Cell Biochemistry Using NMR Spectroscopy

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, mostly in vitro techniques have been used to study subtle and complex biological processes under conditions usually remote from those existing in the cell. We developed a novel in-cell methodology to post-translationally modify interactor proteins and identify the amino acids that comprise the interaction surface of a target protein when bound to the post-translationally modified interactors. Modifying the interactor proteins causes structural changes that manifest themselves on the interacting surface of the target protein and these changes are monitored using in-cell NMR. We show how Ubiquitin interacts with phosphorylated and non-phosphorylated components of the receptor tyrosine kinase (RTK) endocytic sorting machinery: STAM2 (Signal-transducing adaptor molecule), Hrs (Hepatocyte growth factor regulated substrate) and the STAM2-Hrs heterodimer. Ubiquitin binding mediates the processivity of a large network of interactions required for proper functioning of the RTK sorting machinery. The results are consistent with a weakening of the network of interactions when the interactor proteins are phosphorylated. The methodology can be applied to any stable target molecule and may be extended to include other post-translational modifications such as ubiquitination or sumoylation, thus providing a long-awaited leap to high resolution in cell biochemistry

High-Resolution, In Vivo Magnetic Resonance Imaging of Drosophila at 18.8 Tesla

High resolution MRI of live Drosophila was performed at 18.8 Tesla, with a field of view less than 5 mm, and administration of manganese or gadolinium-based contrast agents. This study demonstrates the feasibility of MR methods for imaging the fruit fly Drosophila with an NMR spectrometer, at a resolution relevant for undertaking future studies of the Drosophila brain and other organs. The fruit fly has long been a principal model organism for elucidating biology and disease, but without capabilities like those of MRI. This feasibility marks progress toward the development of new in vivo research approaches in Drosophila without the requirement for light transparency or destructive assays

A tudor domain protein SPINDLIN1 interacts with the mRNA-binding protein SERBP1 and is involved in mouse oocyte meiotic resumption

Mammalian oocytes are arrested at prophase I of meiosis, and resume meiosis prior to ovulation. Coordination of meiotic arrest and resumption is partly dependent on the post-transcriptional regulation of maternal transcripts. Here, we report that, SPINDLIN1 (SPIN1), a maternal protein containing Tudor-like domains, interacts with a known mRNA-binding protein SERBP1, and is involved in regulating maternal transcripts to control meiotic resumption. Mouse oocytes deficient for Spin1 undergo normal folliculogenesis, but are defective in resuming meiosis. SPIN1, via its Tudor-like domain, forms a ribonucleoprotein complex with SERBP1, and regulating mRNA stability and/or translation. The mRNA for the cAMP-degrading enzyme, PDE3A, is reduced in Spin1 mutant oocytes, possibly contributing to meiotic arrest. Our study demonstrates that Spin1 regulates maternal transcripts post-transcriptionally and is involved in meiotic resumption.Ting Gang Chew, Anne Peaston, Ai Khim Lim, Chanchao Lorthongpanich, Barbara B. Knowles, Davor Solte