The Fourth Industrial Revolution and Changes to Working Life : What Supports Adult Employees in Adapting to New Technology at Work?

This chapter aims to increase current understanding of adults' individual learning pathways and needs when adapting to new technology. We review adults' overall technology skills and depict, through chosen examples, how adults have adapted to technological change in their working lives. We present prior research on the challenges that the Fourth Industrial Revolution poses to adults' further education, and based on the Programme for the International Assessment of Adult Competencies (PIAAC), we review adults' problem-solving skills in technology-rich environments. Overall, the findings emphasize the importance of design-based education and the need for companies to flexibly address adults with skill-shortages, who need to develop their problem-solving abilities in technology-rich environments.peerReviewe

Structures of APC/C-CDH1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor

The ubiquitylation of cell-cycle regulatory proteins by the large multimeric anaphase-promoting complex (APC/C) controls sister chromatid segregation and the exit from mitosis. Selection of APC/C targets is achieved through recognition of destruction motifs, predominantly the destruction (D)-box and KEN (Lys-Glu-Asn)-box. Although this process is known to involve a co-activator protein (either Cdc20 or Cdh1) together with core APC/C subunits the structural basis for substrate recognition and ubiquitylation is not understood. Here we investigate budding yeast APC/C using single-particle electron microscopy and determine a cryo-electron microscopy map of APC/C in complex with the Cdh1 co-activator protein (APC/CCdh1) bound to a D-box peptide at ~10 Å resolution. We find that a combined catalytic and substrate-recognition module is located within the central cavity of the APC/C assembled from Cdh1, Apc10—a core APC/C subunit previously implicated in substrate recognition and the cullin domain of Apc2. Cdh1 and Apc10, identified from difference maps, create a co-receptor for the D-box following repositioning of Cdh1 towards Apc10. Using NMR spectroscopy we demonstrate specific D-box–Apc10 interactions, consistent with a role for Apc10 in directly contributing towards D-box recognition by the APC/CCdh1 complex. Our results rationalize the contribution of both co-activator and core APC/C subunits to D-box recognition and provide a structural framework for understanding mechanisms of substrate recognition and catalysis by the APC/C

Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia

Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1b and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1b expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in 40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain