RGG-boxes of the EWS oncoprotein repress a range of transcriptional activation domains

The Ewings Sarcoma Oncoprotein (EWS) interacts with several components of the mammalian transcriptional and pre-mRNA splicing machinery and is also found in the cytoplasm and even on the cell surface. The apparently diverse cellular functions of EWS are, however, not well characterized. EWS harbours a potent N-terminal transcriptional activation domain (the EAD) that is revealed in the context of oncogenic EWS-fusion proteins (EFPs) and a C-terminal RNA-binding domain (RBD) that recruits pre-mRNA splicing factors and may couple transcription and splicing. In contrast to EFPs, the presumed transcriptional role of normal EWS remains enigmatic. Here, we report that multiple RGG-boxes within the RBD are necessary and sufficient for cis-repression of the EAD and that RGG-boxes can also repress in-trans, within dimeric partners. Lys can functionally substitute for Arg, indicating that the basic nature of the Arg side chain is the critical determinant of RGG-box-mediated repression. In addition to the EAD, RGG-boxes can repress a broad range of activation domains (including those of VP16, E1a and CREB), but repression can be alleviated by the simultaneous presence of more than one activation domain. We therefore propose that a key function of RGG boxes within native EWS is to restrict promiscuous activation by the EAD while still allowing EWS to enter functional transcription complexes and participate in other transactions involving pre-mRNAs

Oral Health Literacy among Caregivers in Bangalore City, India

Purpose: To assess caregiver’s oral health literacy of children aged 3-6 years in Bangalore city. Methods: A cross-sectional study was conducted on 635 child/caregiver dyads from a sample of children aged 3-6 years who were selected from anganwadis and preschools in Bangalore city. Demographic details were collected using structured questionnaire. Caregiver literacy was measured using the Rapid Estimate of Adult Literacy in Dentistry (REALD-30). Results: Among 635 child/caregiver dyads, caregiver’s and children’s mean ages were 33.45 years(SD = 3.36) and 5.28 years (SD =0.67), respectively. The mean literacy score was 14.25 (SD= 7.67). The results also indicated that there was an association between socio-demographic variables such as age, education, income, occupation, socioeconomic status and caregivers’ oral health literacy. Conclusion: Caregiver’s oral health literacy is influenced by sociodemographic factors. Oral health literacy is potential determinant and as impact on oral health outcomes in young children

A Rapid Protocol for Somatic Embryogenesis Mediated Regeneration in Banana (Musa Spp.) Cv. Nendran

A simple and rapid protocol for somatic embryogenesis in banana cv. Nendran (AAB) using immature male flowers (IMF) has been developed. The IMF produced palewhite to yellow, globular embryogenic callus on MS medium supplemented with BA (0.05 - 0.50mgL-1) and picloram (0.50 - 2.00mgL-1) with explant response of to 30 per cent. Addition of ascorbic acid (20mgL-1) and Gelrite© (0.45 per cent) to callus induction medium reduced interference from phenolic exudation. Embryogenesis was induced (33.3 to 60 per cent) on semisolid (0.30 per cent Gelrite©) MS medium supplemented with BA 2mgL-1 + IAA 0.5mgL-1. The somatic embryos showed 60-80 per cent germination on half- strength semisolid MS medium with BA 2mgL-1 + IAA 0.5mgL-1. Transfer of germinated embryos to semisolid MS medium supplemented with BA 2mgL-1 + NAA 1mgL-1under 14 h light /8h dark photoperiod resulted in hundred percent conversion to plantlets. This protocol takes merely 6 months for producing plantlets from immature flower buds through somatic embryogenesis, without any intermediate liquid cultures

Metformin Corrects Abnormal Circadian Rhythm and Kir4.1 Channels in Diabetes

Purpose Diabetic retinopathy (DR) is a leading cause of visual impairment. Müller cells in DR are dysfunctional due to downregulation of the inwardly rectifying potassium channel Kir4.1. Metformin, a commonly used oral antidiabetic drug, is known to elicit its action through 5′ adenosine monophosphate-activated protein kinase (AMPK), a cellular metabolic regulator; however, its effect on Kir4.1 channels is unknown. For this study, we hypothesized that metformin treatment would correct circadian rhythm disruption and Kir4.1 channel dysfunction in db/db mice. Methods Metformin was given orally to db/db mice. Wheel-running activity, retinal levels of Kir4.1, and AMPK phosphorylation were determined at study termination. In parallel, rat retinal Müller cell line (rMC-1) cells were treated using metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to assess the effect of AMPK activation on the Kir4.1 channel. Results The wheel-running activity of the db/db mice was improved following the metformin treatment. The Kir4.1 level in Müller cells was corrected after metformin treatment. Metformin treatment led to an upregulation of clock regulatory genes such as melanopsin (Opn4) and aralkylamine N-acetyltransferase (Aanat). In rMC-1 cells, AMPK activation via AICAR and metformin resulted in increased Kir4.1 and intermediate core clock component Bmal-1 protein expression. The silencing of Prkaa1 (gene for AMPKα1) led to decreased Kir4.1 and Bmal-1 protein expression. Conclusions Our findings demonstrate that metformin corrects abnormal circadian rhythm and Kir4.1 channels in db/db mouse a model of type 2 diabetes. Metformin could represent a critical pharmacological agent for preventing Müller cell dysfunction observed in human DR

Enhancement of bioethanol production from lignocellulosic biomass of banana by single batch fermentation using Saccharomyces cerevisiae and native microorganism

Bioethanol production using the lignocellulosic biomass of banana viz., banana raw peel, ripe peel and pseudostem were attempted. Among the three feed stocks, maximum total reducing sugar content of 21.98% was observed in the banana ripe peel.  Pretreatments of the feed stocks with acid resulted in higher lignin removal and increased total reducing sugar content compared to the alkali treatment. Separate Hydrolysis and Fermentation (SHF), Simultaneous Saccharification and Fermentation (SSF) and Single Batch Bioconversion (SBB) were carried out for the fermentation process using Saccharomyces cerevisiae. By SSF fermentation processs, 6.63% of ethanol was produced by Saccharomyces cerevisiae from the untreated samples of banana raw peel. Enhancement of bioethanol production was done using a native cellulolytic microorganism isolated from the degraded banana samples. Using the native microorganism along with Saccharomyces cerevisiae in SBB resulted in 6.88% of bioethanol conversion. This is the first report of using native microorganism for enhanced degradation of cellulose in banana biomass for higher bioethanol production

Algicidal Effects of Green Synthesized Silver Nanoparticles using Tinospora cordifolia on Chlamydomonas reinhardtii

Eco-friendly anti-algal agents are in demand for preventing the growth of unwanted algae. Green synthesized nanoparticles exhibit antimicrobial properties and have been used as a better alternative against chemical and physical processes. In the present study, treatment of silver nitrate with leaf extracts (5% w/v) of Tinospora cordifolia, a plant with proven antimicrobial effects, exhibited UV-visible absorption maxima between 440-460 nm after 1h indicating bioreduction of silver to nanoparticles. The green synthesised silver nanoparticles (5 mgl-1) exhibited inhibition zones against Chlamydomonas reinhardtii in in vitro agar assays. Treatment with green synthesised silver nanoparticles during exponential phase of algal growth resulted in significant reduction in algal population, carbohydrate, protein and chlorophyll contents confirming the anti-algal potential. This is the first report on the growth inhibitory potential of green synthesised silver nanoparticles against green algae

Aging and Urban Mobility in Bandar Sunway: A Holistic Approach

Human longevity is constantly changing the demographic outlook of the world’s population and older people are projected to double in the next 30 years from 11% to 22% of the world’s population. Malaysia is no exception and, like most western and developing nations, the number of Malaysians aged 60 years and above has been gradually rising from the 1970s onwards and is currently estimated to represent 10% of its population. This has created an urgent need to develop age-friendly cities, so that older individuals living in urban areas can have an improved life. It is important that the aging population continues to lead healthy and productive lives as far as possible. In this project, which is a work in progress, we surveyed a suburban community, aged 50 years and above, residing in Bandar Sunway and its vicinity in the state of Selangor Darul Ehsan, Malaysia. The aim was to assess their health and perceptions on mobility through targeted questionnaires, in-depth interviews and focus groups and identify the factors associated with healthy aging in a holistic manner. The overall goal is to promote a healthy mind in a healthy body despite the advancing years. In the preliminary phase we surveyed 73 participants aged between 52 – 85 years and compared responses and clinical parameters for individuals below (N = 36) and ≥ 65 years (N = 37) in age. Based on their Body Mass Index (BMI), the participants were generally healthy with a normal BMI (45%) or slightly overweight (41%) with a higher BMI and blood lipid levels. There were no significant differences in the cognitive assessments between the two age groups (p = 0.945). A majority (70%) of the participants were satisfied with their lives in Bandar Sunway, but some reported several health related issues and chronic diseases. However, this was not a factor that hindered their quality of life. Older adults in Bandar Sunway still preferred driving their own vehicles instead of taking public transports. This was due to several shortfalls in the transportation systems: pricing, schedules of transport, safety, and cleanliness. Preliminary results have identified several aspects of public transportation in urban areas that can be improved to better serve the aging community. In doing so, we anticipate the findings and recommendations will be applicable to a much wider community in Malaysia and other parts of the world. The project is aligned with the theme of improving health and well-being and will provide a model for understanding and dealing with aging in the local community

Medication use problems and factors affecting older adults in primary healthcare

Background: As the largest demographic group utilizing primary healthcare facilities, older adults often face the challenge of managing multiple chronic illnesses, leading to numerous medications. Objective: The present study aims to assess medication use problems among older adults and explore the factors affecting them in primary healthcare settings. Methods: A mixed-method study was conducted to establish a baseline understanding of the perspectives and challenges faced by older adults, with regards to medication use. Translated Medication Use Questionnaire (MedUseQ), a patient-centered tool, was distributed to older adults above 60 in primary healthcare settings to assess their frequency of problems related to medication use. Fifteen semi-structured interviews were conducted to explore this topic in depth. Descriptive and inferential analyses were conducted with quantitative data. Interviews were transcribed verbatim, and thematic analysis was conducted. Quantitative and qualitative findings data were triangulated. Results: The study involved 393 participants. The most common problems with regards to medication use were polypharmacy (55.4%), administration difficulties (48.4%), limited awareness about adverse drug events (47.3%), issues with adherence (46.5%), and accessibility to primary healthcare (42.7%). Approximately 55% were satisfied with the older adult-centered medication use services by pharmacist and doctors. The qualitative findings showed that major factors affecting medication use were forgetfulness, language barriers, lack of awareness, transportation problems, long waiting times, and multiple visits to healthcare facilities. Conclusion: The findings of this study reveal that a significant proportion, around 50%, of the older adult population face challenges with medication use in Penang. These difficulties mainly stem from medication administration, adherence, accessibility, polypharmacy, and inadequate medication knowledge. The qualitative analysis further highlighted several factors that contribute to such medication-related problems. Given the rapidly aging Association of Southeast Asian Nations (ASEAN) population, it is essential to devise effective solutions and strategies to tackle medication use-related issues among older adults.We would like to thank all the participants who have contributed to this study.Scopu

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy