Study Of Protein-Rna Interactions Using Fluorescence Resonance Energy Transfer (fret) And Single-Molecule Fret

In the cell, RNA and protein, interact to form ribonucleoprotein complexes (RNPs) that have vital structural, catalytic and regulatory roles. Despite their functional importance, the mechanistic details and dynamics of RNPs are poorly understood. Single-molecule Fluorescence Resonance Energy Transfer (smFRET) techniques that provide information about heterogeneity and dynamic behaviors of molecules have been developed to investigate inter- and intra-molecular interactions. Here we have used FRET in combination with smFRET to study three very different RNP systems. Alternative splicing is a highly regulated biological process that plays a crucial role in proteomic diversity in eukaryotes. One splicing regulator, PTB, has been proposed to repress splicing by looping RNA between two binding sites. Here, we examined the looping activity of a minimal PTB construct (PTB34) on various RNA oligonucleotides and found that PTB34 requires at least a 15 nucleotide linker between binding sites for efficient looping. A PTB antagonist, Fox-1, has been hypothesized to compete with PTB to reduce looping and promote exon inclusion. Our data suggest that Fox-1 indeed disrupts PTB binding and looping, supporting the hypothesis that Fox-1 breaks RNA looping to enhance splicing of alternative exons. Interactions between ribosomal proteins and ribosomal RNA facilitate the formation of functional ribosomes. Studies of a central junction in 16S rRNA and the primary binding protein that triggers a conformational change, S15, show that mutations that alter the junction dynamics affect 30S assembly. Although partially functional mutants are complemented by over-expression of S15, nonfunctional mutants are not. Comparison of the structural dynamics of these mutants and WT sequence in the presence and absence of S15 revealed specific sequence and structural motifs in the junction that are important for ribosome function. Small non-coding RNAs regulate gene expression in response to biological stimuli through a mechanism that relies on changes in RNA-RNA interactions, for instance switching between two hairpins and an extended duplex. In the cell, proteins, such as Hfq, facilitate the formation of functional RNA structures. Here we show that Hfq acts as a chaperone to overcome high-energy barriers and promote the progression of kissing hairpins through strand displacement to an extended duplex formation

Modelling Locally Changing Variance Structured Time Series Data By Using Breakpoints Bootstrap Filtering

Stochastic processes have applications in many areas such as oceanography and engineering. Special classes of such processes deal with time series of sparse data. Studies in such cases focus in the analysis, construction and prediction in parametric models. Here, we assume several non-linear time series with additive noise components, and the model fitting is proposed in two stages. The first stage identifies the density using all the clusters information, without specifying any prior knowledge of the underlying distribution function of the time series. The effect of covariates is controlled by fitting the linear regression model with serially correlated errors. In the second stage, we partition the time series into consecutive non-overlapping intervals of quasi stationary increments where the coefficients shift from one stable regression relationship to a different one using a breakpoints detection algorithm. These breakpoints are estimated by minimizing the likelihood from the residuals. We approach time series prediction through the mixture distribution of combined error components. Parameter estimation of mixture distribution is done by using the EM algorithm. We apply the method to fish otolith data influenced by various environmental conditions and get estimation of parameters for the model

A Bivariate Distribution with Conditional Gamma and its Multivariate Form

A bivariate distribution whose marginal are gamma and beta prime distribution is introduced. The distribution is derived and the generation of such bivariate sample is shown. Extension of the results are given in the multivariate case under a joint independent component analysis method. Simulated applications are given and they show consistency of our approach. Estimation procedures for the bivariate case are provided

Prenatal Perception of WIC Breastfeeding Recommendation Predicts Breastfeeding Outcomes in Infant\u27s First Year

Objectives Promoting breastfeeding (BF) is a priority of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Prior research found that pregnant mothers who believed WIC recommends BF only (versus BF and formula equally OK) were more likely to initiate BF and continue through 1 month postpartum. We examine whether such mothers are more likely to continue to exclusively BF through 5 months and BF at all through the infant\u27s first year. Methods Data are from the WIC Infant and Toddler Feeding Practices Study-2 (ITFPS-2), a longitudinal study that includes 2,649 mothers who completed prenatal interviews. Four BF outcomes were examined: (a) exclusive BF through 5 months, (b) any BF through 11 months, (c) age of the infant (in days up to 7 months) when formula is initiated, and (d) age of the infant (days up to 13 months) when mother stopped BF. We examined the associations of prenatal belief that WIC recommended BF only (yes/no) with each BF outcome using the Cox regression model to estimate the likelihood of breastfeeding outcomes over time while controlling for prenatal infant feeding intention (IFI) and socio-demographic factors. All analyses accounted for complex survey design effects. Results Of the pregnant mothers, 41% perceived that WIC recommends BF only; 59% perceived that WIC recommends BF and formula equally. Mothers who perceived WIC to recommend BF only were less likely to initiate formula by 7 months than those who perceived WIC recommended BF and formula equally [Hazard Ratio (HR) = 0.84; P \u3c 0.05], after controlling for IFI.WIC perception was a significant predictor only when IFI was not controlled for the other three BF outcomes: stopped exclusive BF through 5 months (HR = 0.83; P \u3c 0.05), stopped any BF through 11 months (HR = 0.80; P \u3c 0.01), and stopped any BF by 13 months (HR = 0.82; P \u3c 0.01). Conclusions Perception of WIC BF recommendation can be a significant predictor of BF outcomes in the infant\u27s first year, possibly by affecting BF intention. Funding Sources ITFPS-2 is funded by the Food and Nutrition Service, U.S. Department of Agriculture (USDA). Support for the study analysis was provided by the Economic Research Service, USDA CRA 58–4000-8–0038-R. Findings and conclusions are those of the authors and should not be construed to represent any official USDA or US Government determination or policy

Adolescent Crash Rates and School Start Times in Two Central Virginia Counties, 2009-2011: A Follow-Up Study to a Southeastern Virginia Study, 2007-2008

Background and Objective: Early high school start times (EHSST) may lead to sleep loss in adolescents ( teens ), thus resulting in higher crash rates. (Vorona et al., 2011). In this study, we examined two other adjacent Virginia counties for the two years subsequent to the above-mentioned study. We again hypothesized that teens from jurisdictions with EHSST (versus later) experience higher crash rates. Methods: Virginia Department of Motor Vehicles supplied de-identified aggregate data on weekday crashes and time-of- day for 16-18 year old (teen) and adult drivers for school years 2009-2010 and 2010-2011 in Henrico and Chesterfield Counties (HC and CC, respectively). Teen crash rates for counties with early (CC) versus later (HC) school start-times were compared using two-sample Z-tests and these compared to adult crash rates using pair-wise tests. Results: Chesterfield teens manifested a statistically higher crash rate of 48.8/1,000 licensed drivers versus Henrico\u27s 37.9/1,000 (p = 0.04) for 2009-2010. For 2010-2011, CC 16-17 year old teens demonstrated a statistically significant higher crash rate (53.2/1,000 versus 42.0/1,000), while for 16-18 teens a similar trend was found, albeit nonsignificant (p = 0.09). Crash peaks occurred 1 hour earlier in the morning and 2 hours earlier in the afternoon in Chesterfield, consistent with commute times. Post hoc analyses found significantly more run-off road crashes to the right (potentially sleep-related) in Chesterfield teens. Adult crash rates and traffic congestion did not differ between counties. Conclusions: Higher teen crash rates occurred in jurisdictions with EHSST, as in our prior study. This study contributes to and extends existing data on preventable teen crashes and high school start times

Factors Influencing Dietary Diversity of Pregnant Women Attending Antenatal Care in Western Regional Hospital, Nepal: A Cross-sectional Study

Introduction: Diet during pregnancy is important to fulfill the nutritional demand of physiological changes as well as to create an environment for fetal development. In Nepal, meal diversity scores of mothers and children are low. The situation of dietary diversity among pregnant women was unknown in the Western Region of Nepal. Thus, this study was conducted to generate evidence regarding the status and determinants of dietary diversity among pregnant women. Methods: It was a cross-sectional study. Systematic random sampling was done to select 282 pregnant women of third trimester attending antenatal care in Western Regional Hospital, Nepal. The semi-structured questionnaires, 24-hour recall tool, and Household Food Insecurity Access Scale were used to collect information from participants. Univariate, bivariate and multivariate analysis was done to assess the status, association as well as strength of association between study variables respectively.   Results: The mean (±SD) Women's Dietary Diversity Score was 4.96 (±1.42). Pregnant women having education level < SLC compared to ≥ SLC were 74.7% less likely to have high dietary diversity to lowest dietary diversity (AOR: 0.253, CI: 0.103 – 0.620, p=0.003). Similarly, pregnant women having an unpaid occupation of husbands compared to paid were 74.5% less likely to have high dietary diversity to lowest dietary diversity (AOR: 0.255, CI: 0.074 – 0.876, p=0.030). Conclusions: Consumption of medium dietary diversity was predominant among pregnant women. The education of pregnant women and the occupation of her husband were the two significantly associated factors with dietary diversity. Keywords: ANC; Dietary diversity; Household Food Security; Nepal; Pregnant women DOI: https://doi.org/10.3126/jkahs.v2i3.2665

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic