Genetic variants of Y chromosome are associated with a protective lipid profile in black men

Objective— Gender and ethnicity modulate the phenotypic expression of cardiovascular risk factors. In particular, men are at higher risk of developing cardiovascular diseases compared to women, whereas black populations of African origin display reduced mortality from coronary heart disease (CHD) as compared to both whites and South Asians. Because the male-specific region (MSY) of the human Y chromosome is an obvious candidate for gender-related differences in the development of cardiovascular diseases, we aimed to identify genetic variants of MSY influencing cardiovascular risk profile in different ethnic groups. Methods and Results— We genotyped 4 polymorphisms of MSY (HindIII±, rs768983 of TBL1Y, rs3212292 of USP9Y, and rs9341273 of UTY genes) in 579 men of different ethnic groups (blacks, South Asians, and whites) from UK and in 301 whites in Italy. We found that the TBL1YA USP9YA haplotype, present only in blacks in whom it represents the most frequent allelic combinations (AA: n=125; all other combinations: n=45), was associated with lower levels of triglycerides (P=0.025) and higher levels of HDL-cholesterol (P=0.005) as compared to the other haplotypes. Conclusion— The TBL1YA USP9YA haplotype of the Y chromosome, present only in black people of African origin, attributes a favorable lipoprotein pattern, likely to contribute to their reduced susceptibility to coronary heart disease. The study evaluated the association of genetic variants of the male-specific region of the Y chromosome with cardiovascular risk factors in different ethnic groups. The most frequently observed haplotype in black people was associated with a favorable lipoprotein pattern, thus contributing to the lower rate of cardiovascular diseases in blacks

Comparing Crowdsourcing and Friendsourcing: A Social Media-Based Feasibility Study to Support Alzheimer Disease Caregivers

BACKGROUND: In the United States, over 15 million informal caregivers provide unpaid care to people with Alzheimer disease (AD). Compared with others in their age group, AD caregivers have higher rates of stress, and medical and psychiatric illnesses. Psychosocial interventions improve the health of caregivers. However, constraints of time, distance, and availability inhibit the use of these services. Newer online technologies, such as social media, online groups, friendsourcing, and crowdsourcing, present alternative methods of delivering support. However, limited work has been done in this area with caregivers. OBJECTIVE: The primary aims of this study were to determine (1) the feasibility of innovating peer support group work delivered through social media with friendsourcing, (2) whether the intervention provides an acceptable method for AD caregivers to obtain support, and (3) whether caregiver outcomes were affected by the intervention. A Facebook app provided support to AD caregivers through collecting friendsourced answers to caregiver questions from participants' social networks. The study's secondary aim was to descriptively compare friendsourced answers versus crowdsourced answers. METHODS: We recruited AD caregivers online to participate in a 6-week-long asynchronous, online, closed group on Facebook, where caregivers received support through moderator prompts, group member interactions, and friendsourced answers to caregiver questions. We surveyed and interviewed participants before and after the online group to assess their needs, views on technology, and experience with the intervention. Caregiver questions were pushed automatically to the participants' Facebook News Feed, allowing participants' Facebook friends to see and post answers to the caregiver questions (Friendsourced answers). Of these caregiver questions, 2 were pushed to crowdsource workers through the Amazon Mechanical Turk platform. We descriptively compared characteristics of these crowdsourced answers with the friendsourced answers. RESULTS: In total, 6 AD caregivers completed the initial online survey and semistructured telephone interview. Of these, 4 AD caregivers agreed to participate in the online Facebook closed group activity portion of the study. Friendsourcing and crowdsourcing answers to caregiver questions had similar rates of acceptability as rated by content experts: 90% (27/30) and 100% (45/45), respectively. Rates of emotional support and informational support for both groups of answers appeared to trend with the type of support emphasized in the caregiver question (emotional vs informational support question). Friendsourced answers included more shared experiences (20/30, 67%) than did crowdsourced answers (4/45, 9%). CONCLUSIONS: We found an asynchronous, online, closed group on Facebook to be generally acceptable as a means to deliver support to caregivers of people with AD. This pilot is too small to make judgments on effectiveness; however, results trended toward an improvement in caregivers' self-efficacy, sense of support, and perceived stress, but these results were not statistically significant. Both friendsourced and crowdsourced answers may be an acceptable way to provide informational and emotional support to caregivers of people with AD

Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression

Histone acetylation is a diagnostic feature of transcriptionally active genes. The proper recruitment and function of histone acetyltransferases (HATs) and deacetylases (HDACs) are key regulatory steps for gene expression and cell cycle. Functional defects of either of these enzymes may lead to several diseases, including cancer. HATs and HDACs thus are potential therapeutic targets. Here we report that garcinol, a polyisoprenylated benzophenone derivative from Garcinia indica fruit rind, is a potent inhibitor of histone acetyltransferases p300 (IC50≈7 μM) and PCAF (IC50≈5 μM) both in vitro and in vivo. The kinetic analysis shows that it is a mixed type of inhibitor with an increased affinity for PCAF compared with p300. HAT activity-dependent chromatin transcription was strongly inhibited by garcinol, whereas transcription from DNA template was not affected. Furthermore, it was found to be a potent inducer of apoptosis, and it alters (predominantly down-regulates) the global gene expression in HeLa cells

Reliability Analysis of PV Inverters Considering Locational Impact

The inverter system is an important piece of equipment for efficiently absorbing the electricity generated from renewable sources and ensuring reliable grid connections. As power electronics advance, inverter conversion efficiency is improving and photovoltaic (PV) energy is becoming a major contributor to the global supply of renewable energy. However, a key consideration is how reliable the PV inverters are. The dependability performance of PV inverters can be influenced by various environmental parameters, such as solar radiation and temperature (collectively referred to as Mission Profile). Given that these conditions vary by location, it is necessary to take them into account when evaluating the dependability performance of a PV inverter. The Mission Profile, including the local solar radiation and surrounding temperature, are important factors determining the lifespan of a PV inverter. This research examines how environmental variables and geographic position affect the dependability performance of PV converters and finds that these elements have a significant bearing on that performance

Performance Analysis for Control of A Unified Power Flow Controller (UPFC) Using MATLAB Simulink

The long transmission system is required to transfer generated power to distribution system. Hence, maximum power transfer devices with flexible operation are essential in transmission system. Thus, it is necessary to add Flexible AC Transmission System (FACTS) devices at the proper locations. Unified Power Flow Controller (UPFC) is the best FACTS transmission system device for ensuring adequate power flow between generating and distribution via transmission lines. The UPFC consists of two converters which likely to work as STATCOM and SSSC to make a proper power flow. In this paper modeling and analysis of UPFC is presented under platform of MATLAB/Simulink. Extensive responses are incorporated in results section with proper analysis under various operating conditions

Treatment of chronic or relapsing COVID-19 in immunodeficiency

BACKGROUND: Patients with some types of immunodeficiency can suffer chronic or relapsing infection with SARS-CoV-2. This leads to morbidity and mortality, infection control challenges and the risk of evolution of novel viral variants. Optimal treatment for chronic COVID-19 is unknown. OBJECTIVE: To characterise a cohort of patients with chronic or relapsing COVID-19 disease and to record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features and treatment response of immune deficient patients with chronic (at least 21 days) or relapsing (at least two episodes) of COVID-19. RESULTS: We identified 31 cases with a median age of 49 years. Underlying immune deficiency was characterised by antibody deficiency with absent or profoundly reduced peripheral B cells; prior anti-CD20 therapy and X-linked agammaglobulinemia were most common. Clinical features of COVID-19 were similar to the general population, but the median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to five episodes of illness. Remdesivir monotherapy (including when given for prolonged courses up to 20 days) was associated with sustained viral clearance in 7/23 (30.4%) clinical episodes whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 monoclonal antibodies resulted in viral clearance in 13/14 (92.8%) episodes. Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise

Cross-platform expression profiling demonstrates that SV40 small tumor antigen activates Notch, Hedgehog, and Wnt signaling in human cells

BACKGROUND: We previously analyzed human embryonic kidney (HEK) cell lines for the effects that simian virus 40 (SV40) small tumor antigen (ST) has on gene expression using Affymetrix U133 GeneChips. To cross-validate and extend our initial findings, we sought to compare the expression profiles of these cell lines using an alternative microarray platform. METHODS: We have analyzed matched cell lines with and without expression of SV40 ST using an Applied Biosystems (AB) microarray platform that uses single 60-mer oligonucleotides and single-color quantitative chemiluminescence for detection. RESULTS: While we were able to previously identify only 456 genes affected by ST with the Affymetrix platform, we identified 1927 individual genes with the AB platform. Additional technical replicates increased the number of identified genes to 3478 genes and confirmed the changes in 278 (61%) of our original set of 456 genes. Among the 3200 genes newly identified as affected by SV40 ST, we confirmed 20 by QRTPCR including several components of the Wnt, Notch, and Hedgehog signaling pathways, consistent with SV40 ST activation of these developmental pathways. While inhibitors of Notch activation had no effect on cell survival, cyclopamine had a potent killing effect on cells expressing SV40 ST. CONCLUSIONS: These data show that SV40 ST expression alters cell survival pathways to sensitize cells to the killing effect of Hedgehog pathway inhibitors

The transcriptional coactivator MAML1 regulates p300 autoacetylation and HAT activity

MAML1 is a transcriptional coregulator originally identified as a Notch coactivator. MAML1 is also reported to interact with other coregulator proteins, such as CDK8 and p300, to modulate the activity of Notch. We, and others, previously showed that MAML1 recruits p300 to Notch-regulated genes through direct interactions with the DNA–CSL–Notch complex and p300. MAML1 interacts with the C/H3 domain of p300, and the p300–MAML1 complex specifically acetylates lysines of histone H3 and H4 tails in chromatin in vitro. In this report, we show that MAML1 potentiates p300 autoacetylation and p300 transcriptional activation. MAML1 directly enhances p300 HAT activity, and this coincides with the translocation of MAML1, p300 and acetylated histones to nuclear bodies