DNMT3A (DNA (cytosine-5-)-methyltransferase 3 alpha)

Review on DNMT3A (DNA (cytosine-5-)-methyltransferase 3 alpha), with data on DNA, on the protein encoded, and where the gene is implicated

Community-based model for the delivery of antiretroviral therapy in Cambodia: a quasi-experimental study protocol.

BACKGROUND: Multi-month dispensing (MMD) is the mainstay mechanism for clinically stable people living with HIV in Cambodia to refill antiretroviral therapy (ART) every 3-6 months. However, less frequent ART dispensing through the community-based ART delivery (CAD) model could further reduce the clients' and health facilities' burden. While community-based services have been recognized as an integral component of HIV response in Cambodia, their role and effectiveness in ART delivery have yet to be systematically assessed. This study aims to evaluate the CAD model's effectiveness on the continuum of care and treatment outcomes for stable people living with HIV in Cambodia. METHODS: We will conduct this quasi-experimental study in 20 ART clinics across the capital city and nine provinces between May 2021 and April 2023. Study sites were purposively selected based on the availability of implementing partners, the number of people living with HIV each clinic serves, and the accessibility of the clinics. In the intervention arm, approximately 2000 stable people living with HIV will receive ART and services from the CAD model. Another 2000 stable people living with HIV in the control arm will receive MMD-a standard care model for stable people living with HIV. The primary outcomes will be retention in care, viral load suppression, and adherence to ART. The secondary endpoints will include health providers' work burden, the model's cost-effectiveness, quality of life, mental health, social support, stigma, and discrimination. We will compare the outcome indicators within each arm at baseline, midline, and endline using descriptive and inferential statistics. We will evaluate the differences between the intervention and control arms using the difference-in-differences method. We will perform economic evaluations to determine if the intervention is cost-effective. DISCUSSION: This study will build the evidence base for future implementation and scale-up of CAD model in Cambodia and other similar settings. Furthermore, it will strengthen engagements with community stakeholders and further improve community mobilization, a vital pillar of the Cambodian HIV response. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04766710 . Registered 23 February 2021, Version 1

Development of a Surface Plasmon Resonance Biosensor for Real-Time Detection of Osteogenic Differentiation in Live Mesenchymal Stem Cells

Surface plasmon resonance (SPR) biosensors have been recognized as a useful tool and widely used for real-time dynamic analysis of molecular binding affinity because of its high sensitivity to the change of the refractive index of tested objects. The conventional methods in molecular biology to evaluate cell differentiation require cell lysis or fixation, which make investigation in live cells difficult. In addition, a certain amount of cells are needed in order to obtain adequate protein or messenger ribonucleic acid for various assays. To overcome this limitation, we developed a unique SPR-based biosensing apparatus for real-time detection of cell differentiation in live cells according to the differences of optical properties of the cell surface caused by specific antigen-antibody binding. In this study, we reported the application of this SPR-based system to evaluate the osteogenic differentiation of mesenchymal stem cells (MSCs). OB-cadherin expression, which is up-regulated during osteogenic differentiation, was targeted under our SPR system by conjugating antibodies against OB-cadherin on the surface of the object. A linear relationship between the duration of osteogenic induction and the difference in refractive angle shift with very high correlation coefficient was observed. To sum up, the SPR system and the protocol reported in this study can rapidly and accurately define osteogenic maturation of MSCs in a live cell and label-free manner with no need of cell breakage. This SPR biosensor will facilitate future advances in a vast array of fields in biomedical research and medical diagnosis

Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

Paget’s disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease

Search for CP violation in the decay B0->D*+-D-+

We report a search for CP-violating asymmetry in B0 -> D*+- D-+ decays. The analysis employs two methods of B0 reconstruction: full and partial. In the full reconstruction method all daughter particles of the B0 are required to be detected; the partial reconstruction technique requires a fully reconstructed D- and only a slow pion from the D*+ -> D0 pi_slow+ decay. From a fit to the distribution of the time interval corresponding to the distance between two B meson decay points we calculate the CP-violating parameters and find the significance of nonzero CP asymmetry to be 2.7 standard deviations.Comment: 4 pages, 3 figure

Elastogenic Protein Expression of a Highly Elastic Murine Spinal Ligament: The Ligamentum Flavum

Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues

Knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Avian influenza is a considerable threat to global public health. Prevention and control depend on awareness and protective behaviours of the general population as well as high risk-groups. This study aims to explore the knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal.</p> <p>Methods</p> <p>The study was based on a cross-sectional study design, using a structured questionnaire administered in face-to-face interviews with 96 poultry workers age 15 and above from the Rupandehi district in Nepal.</p> <p>Results</p> <p>The majority of respondents were male (80%), mean age was 35 (SD = 11.6). Nearly everybody was aware that AI cases had been detected in Nepal and that poultry workers were at risk for infection. The major sources of AI information were radio, TV and newspapers. Knowledge about preventive measures was high with regard to some behaviours (hand washing), but medium to low with regard to others (using cleaning and disinfecting procedures or protective clothing). Poultry workers who got their information from TV and newspapers and those who were more afraid of contracting AI had higher knowledge than those who did not. Being employed as compared to being an owner of a poultry farm as well as having a high level of knowledge was associated with practising more preventive behaviours. While on one hand many specific government control measures found a high degree of acceptance, a majority of study participants also thought that government control and compensation measures as a whole were insufficient.</p> <p>Conclusions</p> <p>The study provides information about knowledge and practices regarding avian influenza among poultry workers in Nepal. It highlights the importance of targeting lack of knowledge as well as structural-material barriers to successfully build preparedness for a major outbreak situation.</p

Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression

<p>Abstract</p> <p>Background</p> <p>We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA).</p> <p>Methods</p> <p>To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for.</p> <p>Results</p> <p>As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan.</p> <p>Conclusions</p> <p>We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation.</p

Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein

The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy