Affects and emotions are used increasingly as (management) tools – also within education and educational policy. The article raises the following questions: What characterises pedagogy and pedagogic ...work? How can we describe affects, moods and feelings? What emotional states occurs when social workers makes professional judgements? It is intended to contribute to the development of concepts and theories, not to recommend specific practical methods.
Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic ...lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.
Using large ALS whole-genome sequencing and post-mortem RNA sequencing datasets (5,987 and 365 tissue samples, respectively), and iPSC-derived motor neurons from 55 individuals, we investigated the role of CAV1/2 expression and enhancer variants in the ALS phenotype.
We report a differential expression analysis between ALS cases and controls for CAV1 and CAV2 genes across various post-mortem brain tissues and three independent datasets. CAV1 and CAV2 expression was consistently higher in ALS patients compared to controls, with significant results across the primary motor cortex, lateral motor cortex, and cerebellum. We also identify increased survival among carriers of CAV1/2 enhancer mutations compared to non-carriers within Project MinE and slower progression as measured by the ALSFRS. Carriers showed a median increase in survival of 345 days.
These results add to an increasing body of evidence linking CAV1 and CAV2 genes to ALS. We propose that carriers of CAV1/2 enhancer mutations may be conceptualised as an ALS subtype who present a less severe ALS phenotype with a longer survival duration and slower progression. Upregulation of CAV1/2 genes in ALS cases may indicate a causal pathway or a compensatory mechanism. Given prior research supporting the beneficial role of CAV1/2 expression in ALS patients, we consider a compensatory mechanism to better fit the available evidence, although further investigation into the biological pathways associated with CAV1/2 is needed to support this conclusion.
Burnout among Danish prison personnel ANDERSEN, DORTE RAABY; ANDERSEN, LARS PETER; ANN GADEGAARD, CHARLOTTE ...
Scandinavian journal of public health,
12/2017, Letnik:
45, Številka:
8
Journal Article
Recenzirano
Objectives The objective of this follow-up study was to investigate associations between individual, occupational and work environment factors and burnout among both uniformed and non-uniformed ...personnel working in the Danish Prison and Probation Service. Methods The participants (N = 4808) with client contact received a questionnaire in 2010 and again in 2011. In 2010, 2843 participants responded to the questionnaire (59.1%), and in 2011, 1741 responded to the questionnaire, yielding a response rate of 61.2% of the baseline population, and 36.2% of the invited population. Burnout and work characteristics were measured with validated scales from the Copenhagen Psychosocial Questionnaire, and data was analysed by logistic regression. Results Risk factors with the highest impact on burnout were work environmental factors: quantitative demands, emotional demands, involvement in and meaning of work. Role conflict, role clarity, social support and demands for hiding emotions had borderline significance. Besides cohabitation, there was no association between individual factors and burnout or between occupational characteristics and burnout. Moreover, there was no association between exposure to threats and violence and burnout. Conclusions: Efforts for preventing burnout ought to be concentrated on reducing the quantitative job-demands, on easing and improving staff–inmate relationships, but also on involvement in and meaning of work. Most work in prison is invisible and the overall goals are in conflict with each other. Management must provide solutions to problems of role conflict and support groups for social support. There is a risk of burnout among both uniformed personnel and non-uniformed personnel working in both open and closed facilities.
Three Na
sites are defined in the Na
-bound crystal structure of Na
, K
-ATPase. Sites I and II overlap with two K
sites in the K
-bound structure, whereas site III is unique and Na
specific. A ...glutamine in transmembrane helix M8 (Q925) appears from the crystal structures to coordinate Na
at site III, but does not contribute to K
coordination at sites I and II. Here we address the functional role of Q925 in the various conformational states of Na
, K
-ATPase by examining the mutants Q925A/G/E/N/L/I/Y. We characterized these mutants both enzymatically and electrophysiologically, thereby revealing their Na
and K
binding properties. Remarkably, Q925 substitutions had minor effects on Na
binding from the intracellular side of the membrane - in fact, mutations Q925A and Q925G increased the apparent Na
affinity - but caused dramatic reductions of the binding of K
as well as Na
from the extracellular side of the membrane. These results provide insight into the changes taking place in the Na
-binding sites, when they are transformed from intracellular- to extracellular-facing orientation in relation to the ion translocation process, and demonstrate the interaction between sites III and I and a possible gating function of Q925 in the release of Na
at the extracellular side.
Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains one of the leading causes of mortality worldwide. The current "gold standard" vaccine Mycobacterium bovis ...BCG has a limited efficacy that wanes over time. The development of a vaccine to boost BCG-induced immunity is therefore a highly active area of research. Mucosal administration of vaccines is believed to provide better protection against pathogens, such as M. tuberculosis, that invade the host via mucosal surfaces. In this study we demonstrate that an intranasal vaccine, comprising the antigenic fusion protein Ag85B-ESAT-6 and the mucosal combined adjuvant vector CTA1-DD/ISCOMs, strongly promotes a Th1-specific immune response, dominated by gamma interferon-secreting CD4-positive T cells. Mucosal administration of Ag85B-ESAT-6 mixed with CTA1-DD/ISCOMs strongly boosted prior BCG immunity, leading to a highly increased recruitment of antigen-specific cells to the site of infection. Most importantly, we observed a significantly (P < 0.001) reduced bacterial burden in the lung compared to nonboosted control animals. Thus, the results demonstrate the effectiveness of mucosal vaccination with Ag85B-ESAT-6 mixed with CTA1-DD/ISCOMs as adjuvant for stimulating TB-specific protective immunity in the lung.
The ectodomain of the matrix 2 protein (M2e) of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst ...human variants of this virus. With the aim of targeting conformational epitopes presumably shared by diverse influenza A viruses, a vaccine (M2e-NSP4) was constructed linking M2e (in its consensus sequence) to the rotavirus fragment NSP4(98-135); due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2e as presented in membranes. M2e-NSP4 was then evaluated side-by-side with synthetic M2e peptide for its immunogenicity and protective efficacy in a murine influenza challenge model. Here we demonstrate that M2e fused to the tetramerizing protein induces an accelerated, augmented and more broadly reactive antibody response than does M2e peptide as measured in two different assays. Most importantly, vaccination with M2e-NSP4 caused a significant decrease in lung virus load early after challenge with influenza A virus and maintained its efficacy against a lethal challenge even at very low vaccine doses. Based on the results presented in this study M2e-NSP4 merits further investigation as a candidate for or as a component of a universal influenza A vaccine.
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