Formation of an SIR-Nucleosome Filament in vitro and Its Modulation by O-Acetyl-ADP-Ribose

It is not possible to clearly visualize how chromatin condenses to heterochromatin in vivo. However, in an in vitro system for Saccharomyces cerevisiae, the requirements for heterochromatin filament formation mirror those found in vivo. Here we report that the nucleosomes and the Sir2, Sir3 and Sir4 proteins, which are required for in vitro filament assembly, are also components of these filaments, confirming that the filaments are SIR-nucleosome filaments. We show the individual localization patterns of the Sir proteins on this SIR-nucleosome filament, and demonstrate that the metabolite, AAR, plays a specific and essential role in promoting the formation of this SIR-nucleosome filament

Anti-malarial and anti-inflammatory effects of Gynura procumbens are mediated by kaempferol via inhibition of glycogen synthase kinase-3ß (GSK3ß)

Gynura procumbens is a medicinal plant, traditionally used to treat inflammation and fever. A yeast-based assay detected GSK3â-inhibitory activity in the aqueous extract of G. procumbens. GSK3â is now known to have a central role in the modulation of host inflammatory response during bacterial infections. In this study, we investigated the involvement of GSK3â in the anti-malarial and anti-inflammatory effects of an aqueous extract of G. procumbens. Our results showed that G. procumbens inhibited growth of P. falciparum 3D7. Consecutive four-day administration of 250 mg/kg body weight (b.w.) G. procumbens resulted in strong chemosuppression and improved survivability in P. berghei-infected mice. B. pseudomallei-infected mice treated with G. procumbens (50 mg/kg b.w.) showed increased survivability. TNF-á and IFN-ã levels in liver and serum of B. pseudomallei-infected mice were lowered by G. procumbens treatment. IL-10 level was higher in serum of G. procumbens-administered infected mice. G. procumbens treatment of P. berghei-and B. pseudomallei-infected animals each resulted in increased hepatic GSK3â (Ser9) phosphorylation. It is noteworthy that kaempferol (one of the compounds in G. procumbens) also inhibited the growth of P. falciparum 3D7; showed strong chemosuppression and improved survivability in P. berghei-infected mice at 5 mg/kg b.w. B. pseudomallei-infected mice treated with kaempferol (10 mg/kg b.w.) showed improved survivability. Concomitantly, the described effects due to kaempferol also involved enhanced GSK3â (Ser9) phosphorylation as observed with G. procumbens. In summary, the observed anti-malarial and anti-inflammatory effects of G. procumbens involved inhibition of GSK3â and kaempferol may in part be responsible for the pharmacological effects

Serving an Indigenous community: Exploring the cultural competence of medical students in a rural setting

Since 2013, medical students from the International Medical University (IMU) in Malaysia have been providing primary healthcare services, under the supervision of faculty members, to the indigenous people living in Kampung Sebir. The project has allowed the students to learn experientially within a rural setting. This study aims to examine the cultural competence of IMU medical students through an examination of their perspective of the indigenous people who they serve and the role of this community service in their personal and professional development. Students who participated in the project were required to complete a questionnaire after each community engagement activity to help them reflect on the above areas. We analysed the responses of students from January to December 2015 using a thematic analysis approach to identify overarching themes in the students’ responses. Students had differing perceptions of culture and worldviews when compared to the indigenous people. However, they lacked the self-reflection skills necessary to understand how such differences can affect their relationship with the indigenous people. Because of this, the basis of their engagement with the indigenous community (as demonstrated by their views of community service) is focused on their agenda of promoting health from a student’s perspective rather than connecting and building relationships first. Students also lacked the appreciation that building cultural competency is a continuous process. The results show that the medical students have a developing cultural competence. The project in Kampung Sebir is an experiential learning platform of great value to provide insights into and develop the cultural competency of participating students. This study also reflects on the project itself, and how the relationship with stakeholders, the competence and diversity of academic staff, and the support of the university can contribute toward training in cultural competence

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions.

Summary Background Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01)

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI