67 research outputs found
Author Correction: Conformational dynamics linked to domain closure and substrate binding explain the ERAP1 allosteric regulation mechanism (Nature Communications, (2021), 12, 1, (5302), 10.1038/s41467-021-25564-w)
The original version of this Article omitted the following from the Acknowledgements: “This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.” This has now been corrected in both the PDF and HTML versions of the Article. © The Author(s) 2023
Rebon Shrimp Powder Addition Influence to Nutritional Values, Organoleptic Properties and Acceptance of Supplementary Food by Children Aged 4-5 Years Old
Malnutrition and stunting prevalence in under-five children in Cirebon City are still high that reach 13.9% and 15.7%. Rebon shrimp (Acetes erythraeus) contains high protein and calcium. Influence of adding rebon shrimp in supplementary food (lemu porridge and steamed sponge) towards nutrition quality was investigated. This study aimed to determine effects of rebon shrimp powder on nutritional values, organoleptic properties and food acceptance. Laboratory test and Nutriservey software were used to measure nutritional value of rebon shrimp powder and nutrition of supplementary food. Organoleptic test used completely randomized design with four treatments (0%, 5%, 10%, 15% shrimp powder) and two repetitions. Respondents were 30 students of Nutrition Studies Program in Cirebon with 7 hedonic scale (organoleptic test) and 50 children aged 4-5 years in integrated health care (acceptance test). As the result, the level of ash, protein and calcium of rebon shrimp powder met the Indonesian National Standard. Energy, protein and calcium significantly increased (p value < 0.05). Nutrient content of steamed sponge per 100 gram with 5% rebon shrimp powder supplied 21.6% energy, 18.9% protein and 25.9% calcium on recommended dietary allowances. Preference level of color, flavor, taste, texture and overall were significantly different. Lemu porridge with 5% rebon shrimp powder was accepted by 80% of the children and the steamed sponge acceptance reached 88%
Biogeochemical networks in the abandoned historical gold mines affecting mobilization and transport of arsenic in Kolar
Enormous water-logging in ancient abandoned mining shafts of Kolar Gold Fields (KGFs), has largely induced the leaching of sulfide-rich gold minerals contaminating the aquifer system with hazardous elements. Transport of these contaminant has posed threat to the health of the urban population of Kolar township. A detailed survey of borewells, covering radius of 10 km of the KGF was carried out during pre and post-monsoon seasons and various parameters were assessed. Almost 80% of the water samples exceeded the regulatory limits of potable water criteria with excess arsenic (As; 12–127 μg/L), fluoride (F; <0.005 μg/L), dissolved salts (>500 mg/L). Water Quality Index (WQI) was used to understand the overall urban groundwater quality. At the centre of sampling circle core, mineral dissolution was found to be the function of pH, induced by acidophilic sulfur oxidizing bacteria. Modelling of predicted microbial metabolic pathways in metagenomics libraries using PICRUSt, indicated complex functional networks. High expression of siderophore proteins (> 2 cm halo in the chrome azurol test) caused Fe-sequestration, secondary Fe-mineral formation and subsequent release of As. Sulfide bearing Au-rich minerals (Arsenopyrite, Scorodite, Jarosite) were bio-weathered leading to release of H3AsO3+ at low pH, resulted in groundwater composition of Ca–HCO3 type and Ca–Na–HCO3 or Ca–Mg–Cl type.Sanitary Engineerin
Current directions in videoconferencing tele-mental health research
The provision of mental health services via videoconferencing tele-mental health has become an increasingly routine component of mental health service delivery throughout the world. Emphasizing the research literature since 2003, we examine (a) the extent to which the field of tele-mental health has advanced the research agenda previously suggested and (b) implications for tele-mental healthcare delivery for special clinical populations. Previous findings have demonstrated that tele-mental health services are satisfactory to patients, improve outcomes, and are probably cost effective. In the very small number of randomized controlled studies that have been conducted to date, tele-mental health has demonstrated equivalent efficacy compared to face-to-face care in a variety of clinical settings and with specific patient populations. However, methodologically flawed or limited research studies are the norm, and thus the research agenda for tele-mental health has not been fully maximized. Implications for future research and practice are discussed
Conformational dynamics linked to domain closure and substrate binding explain the ERAP1 allosteric regulation mechanism
The endoplasmic-reticulum aminopeptidase ERAP1 processes antigenic peptides for loading on MHC-I proteins and recognition by CD8 T cells as they survey the body for infection and malignancy. Crystal structures have revealed ERAP1 in either open or closed conformations, but whether these occur in solution and are involved in catalysis is not clear. Here, we assess ERAP1 conformational states in solution in the presence of substrates, allosteric activators, and inhibitors by small-angle X-ray scattering. We also characterize changes in protein conformation by X-ray crystallography, and we localize alternate C-terminal binding sites by chemical crosslinking. Structural and enzymatic data suggest that the structural reconfigurations of ERAP1 active site are physically linked to domain closure and are promoted by binding of long peptide substrates. These results clarify steps required for ERAP1 catalysis, demonstrate the importance of conformational dynamics within the catalytic cycle, and provide a mechanism for the observed allosteric regulation and Lys/Arg528 polymorphism disease association. © 2021, The Author(s)
Transcriptomic Identification of ADH1B as a Novel Candidate Gene for Obesity and Insulin Resistance in Human Adipose Tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES)
abstract: Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10[superscript -4]) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10[superscript -60]) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10[superscript -9]), BMI (5.4 x 10[superscript -6]), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.011994
A system dynamics model of the community-based rural drinking water supply program (Pamsimas) in Indonesia
The sustainability of the water supply program in developing countries is influenced by many inter-linked and dynamic factors, suggesting the need to analyse the system behaviour of the water supply program. However, no study analyses factors influencing the sustainability of rural drinking water supply programs holistically, and this study aims to fill that gap. This study utilized a system dynamics approach based on a case study of a community-based rural drinking water supply program (PAMSIMAS in Bahasa) in Magelang Regency, Indonesia. Five sustainability aspects were considered in the model development and simulation: Financial, institutional, environmental, technical, and social aspects. Eight scenario analyses related to those five aspects were conducted. The causal loop diagrams suggest that the overall loop in the system is reinforcing, meaning that the improvement in one aspect will improve the overall condition of the system and deterioration in one aspect will reduce the overall condition of the system. Scenario analysis shows that external fund is critical to support the program financially, especially at the beginning of the project when the piped system is being built and water revenue is still low. Scenario and sensitivity analyses revealed that human factors, i.e., the performance of the water board and response and support from the community, positively influence the sustainability of the water supply program. Additionally, the water board plays a key role in accelerating the pipe network growth. Finally, this paper argues that visualising and simulating the causal relationship and dynamic behaviour of the rural water supply program are critical for water stakeholders to better design and implement the water supply program.Sanitary Engineerin
Global vitamin D status and determinants of hypovitaminosis D
This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. Introduction: Vitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. Methods: Six regions of the world were reviewed-Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania-through a survey of published literature. Results: The definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75 nmol-L are prevalent in every region studied whilst levels below 25 nmol-L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. 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EEPD1 promotes repair of oxidatively-stressed replication forks
Unrepaired oxidatively-stressed replication forks can lead to chromosomal instability and neoplastic transformation or cell death. To meet these challenges cells have evolved a robust mechanism to repair oxidative genomic DNA damage through the base excision repair (BER) pathway, but less is known about repair of oxidative damage at replication forks. We found that depletion or genetic deletion of EEPD1 decreases clonogenic cell survival after oxidative DNA damage. We demonstrate that EEPD1 is recruited to replication forks stressed by oxidative damage induced by H2O2 and that EEPD1 promotes replication fork repair and restart and decreases chromosomal abnormalities after such damage. EEPD1 binds to abasic DNA structures and promotes resolution of genomic abasic sites after oxidative stress. We further observed that restoration of expression of EEPD1 via expression vector transfection restores cell survival and suppresses chromosomal abnormalities induced by oxidative stress in EEPD1-depleted cells. Consistent with this, we found that EEPD1 preserves replication fork integrity by preventing oxidatively-stressed unrepaired fork fusion, thereby decreasing chromosome instability and mitotic abnormalities. Our results indicate a novel role for EEPD1 in replication fork preservation and maintenance of chromosomal stability during oxidative stress. © 2023 The Author(s).11Yscopu
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