Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease

An Arab perspective on social media : how banks in Kuwait use instagram for public relations

This study examines the public relations functions of eight Kuwaiti banks listed in the Kuwait Stock Exchange Market (KSEM) that post on their Instagram accounts. It also uses market-size, organization, and individual level predictors to model Instagram postings. A content analysis of 1502 posts revealed the banks use Instagram for promotion, information dissemination, community building, and interactive engagement, in that order of prominence. The findings suggest banks operate at the confluence of visual communication through Instagram and integration of religious sym- bolism to serve a public relations function predicated on image and influence. In doing so, the banks tap into the wellspring of social media use by target publics by navigating a balance between obedience to Allah and meeting bank business objectives. The resulting tension between sacred and secular highlights Arab cultural values and suggests Instagram fosters individualism, which challenges Arab emphasis on collectivism and fractures the notion online platforms can effectively build meaningful relationships that characterize Arab culture. The study posits Instagram is more effective in an Arab context at image building than relationship building, threading the importance of visual communication through social media across Arab culture and global public relations practices

Effect of Low Skeletal Muscle Mass on Post-operative Survival of Patients With Abdominal Aortic Aneurysm: A Prognostic Factor Review and Meta-Analysis of Time-to-Event Data.

OBJECTIVE/BACKGROUND Low psoas muscle mass is associated with increased mortality and morbidity after surgery. Recent evidence has linked low psoas muscle mass with survival after abdominal aortic aneurysm (AAA) repair. The aim of this study was to investigate the prognostic role of low skeletal muscle mass in survival of patients with AAA undergoing open or endovascular aneurysm repair (EVAR). METHODS A review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42018107793). The prognostic factor of interest was degenerative loss of skeletal muscle. A time-to-event data meta-analysis was performed for all cause mortality using the inverse variance method and the results were reported as summary hazard ratio (HR) and 95% confidence interval (CI). Pooled estimates of peri-operative outcome data were calculated using the odds ratio (OR) or risk difference (RD) and 95% CI. Random-effects models of meta-analysis were applied. RESULTS Seven observational cohort studies reporting a total of 1,440 patients were eligible for quantitative synthesis. Patients with low skeletal muscle mass had a significantly higher hazard of mortality than those without low skeletal muscle mass (HR 1.66, 95% CI 1.15-2.40; p = .007). Subgroup analysis including only patients who underwent EVAR showed a marginal survival benefit for patients without low skeletal muscle mass (HR 1.86, 95% CI 1.00-3.43; p = .05). Meta-analysis of two studies found no significant difference in peri-operative mortality (RD 0.04, 95% CI -0.13 to 0.21) and morbidity (OR 1.58, 95% CI 0.90-2.76; p = .11) between patients with and without low skeletal muscle mass. CONCLUSION There is a significant link between low skeletal muscle mass and mortality in patients undergoing AAA repair. Prospective studies validating the use of body composition for risk prediction after aortic surgery are required before this tool can be used to support decision making and patient selection

Nrf2-Mediated System xc- Activation in Astroglial Cells Is Involved in HIV-1 Tat-Induced Neurotoxicity

HIV-associated neurocognitive disorders (HANDs) affect a large part of HIV-infected patients, despite highly active antiretroviral therapy. HANDs occur in the absence of a direct infection of neurons. Nevertheless, viral proteins (e.g., Tat) are capable to cause neuronal dysfunction via oxidative stress, but the cellular pathways leading to HANDs are not yet fully defined. Here, we investigated the effects of Tat on Nrf2-mediated antioxidant response and system xc- expression in U373 human astroglial cells. Moreover, the effect of Tat-producing astrocytes on neuronal cell viability was assessed using SH-SY5Y cells as a culture model. We demonstrated that Tat produced by astrocytes was able to induce Nrf2 activation and system xc- expression in astrocytes, thus reducing cell viability of co-cultured neuronal cells. Furthermore, sulfasalazine, a specific system xc- inhibitor, was able to reduce extracellular glutamate and to prevent the reduction of neuronal viability, thus demonstrating that the neurotoxic effect was dependent on an increased glutamate release through the transporter. Our findings provide evidence of the involvement of astroglial Nrf2/system xc- pathway in the neurotoxicity induced by HIV-1 Tat protein, thereby suggesting how astrocytes may exacerbate neurodegeneration through the conversion of an antioxidant response to excitotoxicity