BVVL/ FL: features caused by SLC52A3 mutations; WDFY4 and TNFSF13B may be novel causative genes

Brown-Vialetto-Van Laere (BVVL) and Fazio-Londe are disorders with amyotrophic lateral sclerosis-like features, usually with recessive inheritance. We aimed to identify causative mutations in 10 probands. Neurological examinations, genetic analysis, audiometry, magnetic resonance imaging, biochemical and immunological testings, and/or muscle histopathology were performed. Mutations in known causative gene SLC52A3 were found in 7 probands. More importantly, only 1 mutated allele was observed in several patients, and variable expressivity and incomplete penetrance were clearly noted. Environmental insults may contribute to variable presentations. Putative causative mutations in other genes were identified in 3 probands. Two of the genes, WDFY4 and TNFSF13B, have immune-related functions. Inflammatory responses were implicated in the patient with the WDFY4 mutation. Malfunction of the immune system and mitochondrial anomalies were shown in the patient with the TNFSF13B mutation. Prevalence of heterozygous SLC52A3 BVVL causative mutations and notable variability in expressivity of homozygous and heterozygous genotypes are being reported for the first time. Identification of WDFY4 and TNFSF13B as candidate causative genes supports conjectures on involvement of the immune system in BVVL and amyotrophic lateral sclerosis

Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability

An Integrated Framework to Study Ecological Tipping Points in Social-Ecological Systems

Sudden regime shifts or tipping points pose a major threat to various ecosystems and people\u27s livelihoods worldwide. However, tipping points are still hard to predict and often occur without warning. To avoid dramatic social-ecological consequences, it is crucial to understand tipping point behaviour and to identify early warning indicators. Previous studies have hardly implemented an integrated social-ecological approach, which has led to a fragmented understanding and oversimplification of tipping point phenomena. Against this background, we present a systemic research framework that harmonizes ecological and social perspectives to gain a mechanistic understanding of tipping point behaviour. We utilize a social-ecological systems (SES) approach to identify drivers, consequences, and feasible preventive strategies. Our proposed framework consists of a retrospective, a comparative and a prospective perspective; each of them utilizes interdisciplinary studies in both sub systems at multiple scales. The research framework was developed by the members of NamTip, an inter- and transdisciplinary research project aiming to understand and manage desertification tipping points in Namibia’s semi-arid rangelands. The NamTip project represents a practical implementation of the research framework, that uses an integrated, social-ecological study design combining the threefold approach with dynamic modelling. This includes analyses of time-series and archival data, experimental and observational studies, as well as scenario development and exploration of decision-making with local farmers. After the initial practical implementation and with our ongoing evaluation, we are convinced that such an ambitious and complex framework will guide the way to a profound understanding of tipping point phenomena and feasible management options

Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis

Background: Omega-3 fatty acids (FAs) have been suggested as a beneficial supplement in chronic kidney disease (CKD) patients, but the results of randomized clinical trials (RCTs) are controversial. We conducted a systematic review and meta-analysis to evaluate all the RCTs about the impact of omega-3 FAs supplementation on cardiometabolic outcomes and oxidative stress parameters in patients with CKD. Methods: We performed a systematic database search in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Central, up to May 2020. We included all placebo-controlled randomized trials that assessed the effect of omega-3 FAs supplementation on any cardiometabolic outcomes: blood pressure, total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) or triglycerides (TG) and oxidative stress parameters. Data were pooled using DerSimonian�Laird�s random-effects model. Results: Finally, thirteen articles met the inclusion criteria for this review omega-3 FAs supplementation significantly decrease TC (SMD: -0.26; 95 CI: � 0.51, � 0.02; I2 = 52.7), TG (SMD: -0.22; 95 CI: � 0.43, � 0.02; I2 = 36.0) and Malondialdehyde (MDA) levels (SMD: -0.91; 95 CI: � 1.29, � 0.54; I2 = 00.0) and also significantly increase superoxide dismutase (SOD) (SMD: 0.58; 95 CI: 0.27, 0.90; I2 = 00.0) and Glutathione peroxidase (GPx) (SMD: 0.50; 95 CI: 0.14, 0.86; I2 = 00.0) activities. However our results show that omega-3 FAs supplementation have no significant effects on HDL, LDL and blood pressure. Conclusion This systematic review and meta-analysis supports current evidence for the clinical benefit of omega-3 FAs intake to improve cardiometabolic parameters in CKD patients. However, well-designed RCTs still needed to provide a conclusive picture in this field. © 2021, The Author(s)

A family presenting with multiple endocrine neoplasia type 2B: A case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple endocrine neoplasia 2B, a rare autosomal dominant syndrome, is characterized by early onset of medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus and mucosal neuromas of the tongue, lips, inner cheeks and inner eyelids. Gangliomatosis of the gastrointestinal tract and its complications may also occur in patients with this disease.</p> <p>Case presentation</p> <p>We present the case of a 16-year-old Persian man diagnosed as having a non-invasive form of multiple endocrine neoplasia 2B (medullary thyroid cancer, mucosal neuroma of the tongue, lips and inner eyelids). Our patient, who had a positive family history of medullary thyroid cancer, was of normal height with no signs of marfanoid habitus.</p> <p>Conclusions</p> <p>Ophthalmological and oral manifestations of multiple endocrine neoplasia 2B, as in the case of our patient, are rare presentations of the disease; unfortunately in the case of our patient his condition had not been noted and acted upon until he presented to our department. The diagnosis in our patient's case was made only after his mother presented with the same condition. As a result, we emphasize that physicians should pay more attention to the oral and ocular signs of multiple endocrine neoplasia 2B in order to diagnose this fatal syndrome at an earlier phase.</p

Worker remittances and the global preconditions of ‘smart development’

With the growing environmental crisis affecting our globe, ideas to weigh economic or social progress by the ‘energy input’ necessary to achieve it are increasingly gaining acceptance. This question is intriguing and is being dealt with by a growing number of studies, focusing on the environmental price of human progress. Even more intriguing, however, is the question of which factors of social organization contribute to a responsible use of the resources of our planet to achieve a given social result (‘smart development’). In this essay, we present the first systematic study on how migration – or rather, more concretely, received worker remittances per GDP – helps the nations of our globe to enjoy social and economic progress at a relatively small environmental price. We look at the effects of migration on the balance sheets of societal accounting, based on the ‘ecological price’ of the combined performance of democracy, economic growth, gender equality, human development, research and development, and social cohesion. Feminism in power, economic freedom, population density, the UNDP education index as well as the receipt of worker remittances all significantly contribute towards a ‘smart overall development’, while high military expenditures and a high world economic openness are a bottleneck for ‘smart overall development’

Steroid-free medium discloses oestrogenic effects of the bisphosphonate clodronate on breast cancer cells

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

IT Outsourcing in Finnish Business

This paper reviews the characteristics and magnitude of information technology (IT) outsourcing as well as studies its labor productivity effects with a representative sample of Finnish businesses. Depending on the IT task in question, on average from one-third to two-thirds of IT has been outsourced; of the ten categories considered, the development of non-Internet business-to-business applications (e.g., EDI) is the leading activity in this respect. The various dimensions of IT outsourcing are all highly positively correlated. After controlling for industry and regional effects as well as characteristics of firms and their employees, it is found that an externally-supported computer user is about 20% more productive than an otherwise similar worker without a computer, which corresponds to about 5% output elasticity of outsourced IT; the effect of internally-supported computer use is not statistically significantly different for zero, and it is also several times smaller in magnitude. While the issues of causality, timing, self-selection, and unobserved firm heterogeneity are not fully addressed, the findings nevertheless suggest that IT outsourcing may have significant economic consequences