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Ataxin-2 (human gene symbol ATXN2) acts during stress responses, modulating mRNA translation and nutrient metabolism. Ataxin-2 knockout mice exhibit progressive obesity, dyslipidemia, and insulin resistance. Conversely, the progressive ATXN2 gain of function due to the fact of polyglutamine (polyQ) expansions leads to a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2) with early adipose tissue loss and late muscle atrophy. We tried to understand lipid dysregulation in a SCA2 patient brain and in an authentic mouse model. Thin layer chromatography of a patient cerebellum was compared to the lipid metabolome of Atxn2-CAG100-Knockin (KIN) mouse spinocerebellar tissue. The human pathology caused deficits of sulfatide, galactosylceramide, cholesterol, C22/24-sphingomyelin, and gangliosides GM1a/GD1b despite quite normal levels of C18-sphingomyelin. Cerebellum and spinal cord from the KIN mouse showed a consistent decrease of various ceramides with a significant elevation of sphingosine in the more severely affected spinal cord. Deficiency of C24/26-sphingomyelins contrasted with excess C18/20-sphingomyelin. Spinocerebellar expression profiling revealed consistent reductions of CERS protein isoforms, Sptlc2 and Smpd3, but upregulation of Cers2 mRNA, as prominent anomalies in the ceramide–sphingosine metabolism. Reduction of Asah2 mRNA correlated to deficient S1P levels. In addition, downregulations for the elongase Elovl1, Elovl4, Elovl5 mRNAs and ELOVL4 protein explain the deficit of very long-chain sphingomyelin. Reduced ASMase protein levels correlated to the accumulation of long-chain sphingomyelin. Overall, a deficit of myelin lipids was prominent in SCA2 nervous tissue at prefinal stage and not compensated by transcriptional adaptation of several metabolic enzymes. Myelination is controlled by mTORC1 signals; thus, our human and murine observations are in agreement with the known role of ATXN2 yeast, nematode, and mouse orthologs as mTORC1 inhibitors and autophagy promoters.
The interdependence of selective cues during development of regulatory T cells (Treg cells) in the thymus and their suppressive function remains incompletely understood. Here, we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-181a-1 and miR-181b-1 (miR-181a/b-1) during late T-cell development with very high levels of expression during thymocyte selection, followed by massive down-regulation in the periphery. Loss of miR-181a/b-1 resulted in inefficient de novo generation of Treg cells in the thymus but simultaneously permitted homeostatic expansion in the periphery in the absence of competition. Modulation of T-cell receptor (TCR) signal strength in vivo indicated that miR-181a/b-1 controlled Treg-cell formation via establishing adequate signaling thresholds. Unexpectedly, miR-181a/b-1–deficient Treg cells displayed elevated suppressive capacity in vivo, in line with elevated levels of cytotoxic T-lymphocyte–associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral Treg cells. Therefore, we propose that intrathymic miR-181a/b-1 controls development of Treg cells and imposes a developmental legacy on their peripheral function.
B-cell development and function depend on stage-specific signaling through the B-cell antigen receptor (BCR). Signaling and intracellular trafficking of the BCR are connected, but the molecular mechanisms of this link are incompletely understood. Here, we investigated the role of the endosomal adaptor protein and member of the LAMTOR/Ragulator complex LAMTOR2 (p14) in B-cell development. Efficient conditional deletion of LAMTOR2 at the pre-B1 stage using mb1-Cre mice resulted in complete developmental arrest. Deletion of LAMTOR2 using Cd19-Cre mice permitted analysis of residual B cells at later developmental stages, revealing that LAMTOR2 was critical for the generation and activation of mature B lymphocytes. Loss of LAMTOR2 resulted in aberrant BCR signaling due to delayed receptor internalization and endosomal trafficking. In conclusion, we identify LAMTOR2 as critical regulator of BCR trafficking and signaling that is essential for early B-cell development in mice.
The dissertation studied reused Roman coins (AD 100 – 400) that were found in medieval cemeteries (AD 400 – 1400) in the territory of Serbia. The evaluation process was traced through three different periods and cultural contexts: (1) in the period of Roman domination in the central Balkans (AD 1 – 400), i.e. the “primary context” of their use and circulation; (2) in the time of transition from the late antiquity to early medieval period (AD 400 – 700); and (3) in the high and late Middle Ages (AD 900 – 1400), where the last two were considered to be a “secondary context” in which the Roman coins were no longer a valid currency.
It was observed that the reused Roman coins, as a distinctive category of archaeological finds, impose a necessity for reconsideration of the relationship between the disciplines of archaeology and numismatics; encouraging a greater cooperation and discussion between the two. Considering the use and evaluation of Roman coins in their “primary context”, it is possible to presume that the strength of the political Roman system was the crucial factor in the formation and maintaining the stability of the value of Roman coins. The act of reuse should not be automatically equalized with recycling; implying only to use value, but at the same time it was not possible to assume that the value was formed only on a purely symbolical level. The (re)use of Roman coins in the funeral practices from c. AD 400 to 700 was considered to be a part of wider and occasional practice of incorporating older Roman issues in the coin pool by the “barbarian” or Byzantine authorities. It could be then concluded that the value of Roman coins was understood more as a potential attribute than as a fixed category; enabling one to simultaneously “overvalue “ and “undervalue” these objects. In the period from c. AD 900 to 1400, the reuse of Roman coins was detected only within the cemeteries of the peasantry and in a context of gradual increase of general coin use in the central Balkan communities of the Middle Ages. This was understood as an indicator that the Roman coins were not perceived as particularly valuable per se, but since the were recognized as category of objects that became more important in defining social relationships they were then incorporated in the funeral rituals and reinterpreted by the medieval population.
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).
hallmark of ageing is the redistribution of body fat. Particularly, subcutaneous fat decreases paralleled by a decrease of skin collagen I are typical for age-related skin atrophy. In this paper, we hypothesize that collagen I may be a relevant molecule stimulating the differentiation of adipose-derived stem cells (ASCs) into adipocytes augmenting subcutaneous fat. In this context lipogenesis, adiponectin, and collagen I receptor expression were determined. Freshly isolated ASCs were characterized by stemness-associated surface markers by FACS analysis and then transdifferentiated into adipocytes by specific medium supplements. Lipogenesis was evaluated using Nile Red staining and documented by fluorescence microscopy or quantitatively measured by using a multiwell spectrofluorometer. Expression of adiponectin was measured by real-time RT-PCR and in cell-free supernatants by ELISA, and expression of collagen I receptors was observed by western blot analysis. It was found that supports coated with collagen I promote cell adhesion and lipogenesis of ASCs. Interestingly, a reverse correlation to adiponectin expression was observed. Moreover, we found upregulation of the collagen receptor, discoidin domain-containing receptor 2; receptors of the integrin family were absent or downregulated. These findings indicate that collagen I is able to modulate lipogenesis and adiponectin expression and therefore may contribute to metabolic dysfunctions associated with ageing.
The information and communication technology (ICT) sector within the Netherlands is a major driver of globalization, the country’s economic growth and innovation. The Dutch ICT sector’s performance is increasingly becoming dependent upon employee driven innovations in order to address the needs of the sectors they service. In other words, the ICT sector within the Netherlands is largely dependent upon the performance and innovative capacity of its employees; both of which are functions of employee engagement. Given the high demand, and low supply of talent within this sector, ICT organizations need to develop innovative ways to enhance the performance capacities of its people. Developing an engaged and highly innovative workforce seems to be an efficient way to activate employees’ performance. As such, the aim of this paper was to investigate the mediating function of employee driven innovative work behaviors in the relationship between work engagement and task performance within the a Dutch ICT consulting firm. A cross-sectional survey-based research design, employing a census-based sampling method, was employed to obtain data from a global ICT consulting firm within the Netherlands (n = 232). The Utrecht Work Engagement Scale, the Innovative Work Behavior Scale and the Task Performance Scale was used to assess the associative subjective experiences of ICT employees. The results showed that work engagement is a significant driver for innovative work behaviors, which in turn affects the task performance of employees. Further, innovative work behaviors are therefore important to translate the engaging energies of employees into performance. This paper discusses the theoretical and practical implications of these findings.
Problematisation: The credibility and transparency of industrial and organisational psychological (IOP) research within South Africa was recently challenged by Efendic and Van Zyl (2019). The authors briefly showed inconsistencies in statistical results reported by authors of the South African Journal of Industrial Psychology (SAJIP), that various studies were insufficiently powered, that best-practice guidelines for the reporting of results were mostly only partially followed and that no transparency exists with regard to the research process. They demonstrated that authors of the SAJIP may knowingly or unknowingly be engaging in questionable research practices, which directly affects the credibility of both the discipline and the journal. Furthermore, they suggested practical guidelines for both authors and the SAJIP on how this could be managed.
Implications: Based on these suggestions, the authors invited prominent members of the IOP scientific community to provide scholarly commentary on their paper in order to aid in the development of ‘a clear strategy on how [the confidence crisis in IOP] could be managed, what the role of SAJIP is in this process and how SAJIP and its contributors could proactively engage to address these issues’. Seven members of the editorial board and two international scholars provided commentaries in an attempt to further the debate about the nature, causes, consequences and management of the credibility crisis within the South African context.
Purpose: The purpose of this final rebuttal article was to summarise and critically reflect on the commentaries of the nine articles to advance the debate on the confidence crisis within the South African IOP discipline.
Recommendations: All SAJIP’s stakeholders (authors, editors, reviewers, the publication house, universities and the journal) can play an active role in enhancing the credibility of the discipline. It is suggested that SAJIP should develop a clear and structured strategy to promote credible, transparent and ethical research practices within South Africa.
Orientation: The purpose of this editorial was to provide an introduction and a general overview of the special issue on Open Science Practices: A Vision for the Future of SAJIP, as hosted in the 45th edition of the South African Journal of Industrial Psychology (SAJIP). Specifically, the aim was to provide a viable, practical and implementable strategy for enhancing the scientific credibility, transparency and international stature of SAJIP.
Rezension zu: Psychology of Retention:Theory, Research and Practice / Melinde Coetzee, Ingrid L. Potgieter and Nadia Ferreira (Eds.), ISBN:978-3-319-98919-8 Publisher:Springer Nature, 2018, R1600 (Preis SA)