Stimulating the innovation potential of 'routine' workers through workplace learning

Governments worldwide seek to upgrade the ‘basic skills' of employees deemed to have low literacy and numeracy, in order to enable their greater productivity and participation in workplace practices. A longitudinal investigation of such interventions in the United Kingdom has examined the effects on employees and on organizations of engaging in basic skills programmes offered in and through the workplace. ‘Tracking’ of employees in selected organizational contexts has highlighted ways in which interplay between formal and informal workplace learning can help to create the environments for employees in lower grade jobs to use and expand their skills. This workplace learning is a precondition, a stimulus and an essential ingredient for participation in employee-driven innovation, as workers engage with others to vary, and eventually to change, work practices. © 2010, SAGE Publications. All rights reserved

Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions

Understanding the drivers of compartmentalized and sustained inflammation in the brain of progressive multiple sclerosis (PMS) remains elusive. To investigate the interplay between inter- and intra-cellular molecular mechanisms in white matter (WM) lesions, we integrated single-cell transcriptome and chromatin accessibility data from PMS lesions with spatial transcriptomics of chronic active lesion borders. We identified a PMS-specific oligodendrocyte genetic program governed by the Krüppel-like factor and specificity protein (KLF/SP) gene family, implicated in myelination and stress-induced iron uptake. Additionally, we found high expression of transferrin gene (TF) and its receptor megalin (LRP2) across lesion types, suggesting autocrine communication of iron uptake potential related to iron rim lesion in smoldering MS. Additionally, inflammatory phenotype of oligodendrocytes expressing osteopontin gene and complement were observed at chronic active lesion edges. Inside the chronic active lesion, the axonal damage biomarker, neurofilament light (NFL) gene expression was upregulated, and an astrocytic-neuronal axis through fibroblast growth factor (FGF) signaling (FGFR3-FGF13) was present. Additionally, a metabolic astrocyte phenotype at the lesion border potentially segregates inflammation areas. We also identified two distinct B cell co-expression networks with different locations and gene expressions, preferring different lesion types. Overall, singlecell multi-omics enabled the identification of specific cell types with unique molecular profiles, cell-cell communications, and spatial context, contributing to lesion fate.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202

Aquaporin-4 and brain edema.

Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. Experiments using AQP4-null mice provide strong evidence for AQP4 involvement in cerebral water balance. AQP4-null mice are protected from cellular (cytotoxic) brain edema produced by water intoxication, brain ischemia, or meningitis. However, AQP4 deletion aggravates vasogenic (fluid leak) brain edema produced by tumor, cortical freeze, intraparenchymal fluid infusion, or brain abscess. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 deletion also worsens obstructive hydrocephalus. Recently, AQP4 was also found to play a major role in processes unrelated to brain edema, including astrocyte migration and neuronal excitability. These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury

Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes

OBJECTIVE: Here, we applied a multi-omics approach (i) to examine molecular pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and (ii) to translate these findings to the CSF proteome in order to identify molecules that are differentially expressed among MS subtypes. METHODS: To relate differentially expressed genes in MS lesions to de- and remyelination, we compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced de- and remyelination. Protein products of the overlapping orthologous genes were measured within the CSF by quantitative proteomics, parallel reaction monitoring (PRM). Differentially regulated proteins were correlated with molecular markers of inflammation by using MesoScale multiplex immunoassay. Expression kinetics of differentially regulated orthologous genes and proteins were examined in the CPZ model. RESULTS: In the demyelinated and remyelinated corpus callosum, we detected 1239 differentially expressed genes; 91 orthologues were also differentially expressed in MS lesions. Pathway analysis of these orthologues suggested that the TYROBP (DAP12)-TREM2 pathway, TNF-receptor 1, CYBA and the proteasome subunit PSMB9 were related to de- and remyelination. We designed 129 peptides representing 51 orthologous proteins, measured them by PRM in 97 individual CSF, and compared their levels between relapsing (n = 40) and progressive MS (n = 57). Four proteins were differentially regulated among relapsing and progressive MS: tyrosine protein kinase receptor UFO (UFO), TIMP-1, apolipoprotein C-II (APOC2), and beta-2-microglobulin (B2M). The orthologous genes/proteins in the mouse brain peaked during acute remyelination. UFO, TIMP-1 and B2M levels correlated inversely with inflammation in the CSF (IL-6, MCP-1/CCL2, TARC/CCL17). APOC2 showed positive correlation with IL-2, IL-16 and eotaxin-3/CCL26. CONCLUSIONS: Pathology-based multi-omics identified four CSF markers that were differentially expressed in MS subtypes. Upregulated TIMP-1, UFO and B2M orthologues in relapsing MS were associated with reduced inflammation and reflected reparatory processes, in contrast to the upregulated orthologue APOC2 in progressive MS that reflected changes in lipid metabolism associated with increased inflammation

A produção sobre aprendizagem informal nas organizações no Brasil: mapeando o terreno e rastreando possibilidades futuras

A aprendizagem informal é entendida como aquela baseada na experiência intencional, mas não formalmente estruturada; induzida por um processo de reflexão crítica, ação, pró-atividade e criatividade; incrustada no contexto organizacional e nas práticas cotidianas. Pode ser planejada ou não, embora envolva algum grau de consciência de quem aprende. Sua relevância para o ambiente de trabalho tem sido atestada por vários autores. Este trabalho tem como objetivo identificar, descrever e analisar a produção a respeito dessa temática no Brasil, no período de 2006 a 2012. O conjunto de 21 artigos selecionados para fazer parte desta revisão reúne estudos teóricos e empíricos publicados em periódicos nacionais da área de Administração e avaliados com conceito B2 ou superior pelo WebQualis da CAPES. O estudo envolveu duas etapas. Numa primeira etapa definiram-se as fontes de dados e amostra a ser trabalhada. Uma segunda etapa consistiu na análise dos artigos a partir das seguintes dimensões: foco dos estudos (origem, tema e objetivos), nível de aprendizagem, autores referenciados, perspectivas teóricas, posicionamentos epistemológicos, tipos de pesquisa, dados de contexto da produção e principais achados. Os resultados mostram uma produção dispersa que ainda precisa ser aprimorada em relação aos arcabouços teóricos tomados como referência para o aprofundamento do tema