Plasmid optimization and the localization of the binding site of GPS2-UBC13

The GPS2 protein (G-protein pathway suppressor 2) is a product of the mammalian gps2 gene. It was originally identified and characterized in the context of G protein mitogen-activated protein kinase (MAPK) signaling pathways. Several studies have linked GPS2 with the inhibition of the ubiquitin conjugating enzyme UBC13. GPS2-mediated inhibition of UBC13 regulates several metabolic and inflammatory pathways. It has been shown that a lack of GPS2 is correlated with an increase in adiposity and inflammation due to the aberrant activity of UBC13 affected pathways. Therefore, understanding the relationship between UBC13 and GPS2 will provide further understanding of the molecular processes involved in adipose tissue levels, inflammation and downstream molecular responses. In this study, we attempt to determine the molecular determinants of GPS2 interaction with UBC13 by optimizing the protein expression protocol required to produce GPS2 protein expression in Escherichia coli in quantities viable for biochemical and structural assays. Our results indicate that optimization of the gps2 sequence is required for efficient GPS2 protein expression in E. coli cells. Thanks to this optimization we have been able to successfully express GPS2 full length and several fragments, however, further optimization will be required for assessing GPS2-UBC13 molecular binding via in vitro binding assays

A Novel Dynamic Appliance Clustering Scheme in a Community Home Energy Management System for Improved Stability and Resiliency of Microgrids

Power scheduling of domestic appliances is a vital preference for bridging the gap between demand and generation of electricity in a microgrid. For a stable microgrid, an acceptable mechanism must reduce the peak to average ratio (PAR) of power demand with supplementary benefits for consumers as reduced electricity charges. Recent studies have focused on PAR and cost reduction for a small consumer population. Furthermore, researchers have mainly considered homogeneous consumer loads. This study focuses on residential power scheduling for electricity cost reduction for consumers and load profile PAR curtailment for a relatively large consumer population with non-homogeneous loads. A sample population of 1000 consumers from various classes of society is considered. The proposed dynamic clustered community home energy management system (DCCHEMS) allows the clustering of appliances based on time overlap criteria. Comparatively flatter power demand is attained by utilizing the clustered appliances in conjunction with particle swarm optimization under the influence of user-defined constraints. Modified inclined block rates with real-time electricity pricing strategies are deployed to minimize the electricity costs. DCCHEMS achieved higher efficiency rates in contrast to the traditional non-clustering and static clustering optimization schemes. An improvement of 21% in peak to average ratio, 4% in cost reduction, and 19% in variance to mean ratio is obtained

The AGE-RAGE axis in an Arab population: The United Arab Emirates Healthy Futures (UAEHFS) pilot study

© 2017 The Authors Aims The transformation of the United Arab Emirates (UAE) from a semi-nomadic to a high income society has been accompanied by increasing rates of obesity and Type 2 diabetes mellitus. We examined if the AGE-RAGE (receptor for advanced glycation endproducts) axis is associated with obesity and diabetes mellitus in the pilot phase of the UAE Healthy Futures Study (UAEHFS). Methods 517 Emirati subjects were enrolled and plasma/serum levels of AGE, carboxy methyl lysine (CML)-AGE, soluble (s)RAGE and endogenous secretory (es)RAGE were measured along with weight, height, waist and hip circumference (WC/HC), blood pressure, HbA1c, Vitamin D levels and routine chemistries. The relationship between the AGE-RAGE axis and obesity and diabetes mellitus was tested using proportional odds models and linear regression. Results After covariate adjustment, AGE levels were significantly associated with diabetes status. Levels of sRAGE and esRAGE were associated with BMI and levels of sRAGE were associated with WC/HC. Conclusions The AGE-RAGE axis is associated with diabetes status and obesity in this Arab population. Prospective serial analysis of this axis may identify predictive biomarkers of obesity and cardiometabolic dysfunction in the UAEHFS

Seed Biology and Phytochemistry for Sustainable Future

The ranking of seeds represents remarkable transition phase for photosynthasis and sexual reproduction, this phase is complex & successful method for sexual reproduction in vascular plants. As we know that seed containe the genetic repository of past & potential for its perpetuation in the future. The dormancy in seeds induced by desciccation & the hormone abscisic acid (ABA) till the condition in growth become favorable. The well developed seeds eliminates requirement of water during sexual reproduction & allows fertilization events to occur over long distances. Germination of seeds in particular situation and season is determines the interaction between dormancy and relating factors like phytochemical development to give healthy bioactives, which strongly influence on the termination of dormancy or initiatin of germination and seedling in many plant species like photo-hormons, light, temperature, water, neutrients and mechanical cuse. Seeds of particular plants needs difreent pretreatment to give vigor seedlings even in production so far. The entiteled chapter represents amulgumation of agriculturists and life scientists. Recent significant progress has been endorsed in seed physiology to solve the practical issues constantly associated with the seeds. The aim & objective of this articale is to enlighten the reader, not only about the different aspects of the seed physiology it also includes the development of bioactive (secondary metabolites) in the healthy seeds. This resorce of pice will help researcher to sencitize about the type of healthy bioactive available in the shalls of seedlings. This could be the reason to isolate the biomolecules from a well evaluate seeds, seed evalution not only the sorce to get healthy crops in agricultural scince it also helps so for a phytochemist to get theuraputicaly active biomolecules, without destroying the nature, which could be the value added thought to combat with the burning issues associated with the existing situation (COVID Omicron, viral infection and all kinds of disorder associated with the immune system). Henceforth, endorsed personage to give real-time attention to plant propagation, particularly for indigenous tree species and seedling multiplication should be regarded as a primary need to make not only a sustainable environment but also become a treasure to fulfill the needs of industry application in the field of agriculture plus R & D

Tuberculosis suspicion and knowledge among private and public general practitioners: Questionnaire Based Study in Oman

<p>Abstract</p> <p>Background</p> <p>Early detection of smear positive TB cases by smear microscopy requires high level of suspicion of TB among primary care physicians. The objective of this study is to measure TB suspicion and knowledge among private and public sector general practitioners using clinical vignette-based survey and structured questionnaire.</p> <p>Methods</p> <p>Two questionnaires were distributed to both private and public GPs in Muscat Governorate. One questionnaire assessed demographic information of the respondent and had 10 short clinical vignettes of TB and non-TB cases. The second questionnaire had questions on knowledge of TB, its diagnosis, treatment, follow up and contact screening based on Ministry of Health policy. TB suspicion score and TB Knowledge score were computed and analyzed.</p> <p>Results</p> <p>A total of 257 GPs participated in the study of which 154 were private GPs. There was a significant difference between private and public GPs in terms of age, sex, duration of practice and nationality. Among all GPs, 37.7% considered TB as one of the three most likely diagnoses in all 5 TB clinical vignettes. Private GPs had statistically significantly lower TB suspicion and TB knowledge scores than public GPs.</p> <p>Conclusion</p> <p>In Oman, GPs appear to have low suspicion and poor knowledge of TB, particularly private GPs. To strengthen TB control program, there is a need to train GPs on TB identification and adopt a Private Public Mix (PPM) strategy for TB control.</p

Immigrants and health system challenges to TB control in Oman

<p>Abstract</p> <p>Background</p> <p>During the past three decades, Oman has made significant progress in controlling TB within it's borders. However, the national TB control program elimination target has yet to be reached. This study aims to explore the perceived roles played by the immigrant population and the private health sector in relation to TB control in Oman.</p> <p>Methods</p> <p>We conducted seventeen interviews with different health care providers. The verbatim transcripts were processed using content analysis.</p> <p>Results</p> <p>Three main themes emerged. Firstly the threat of repatriation faced by underprivileged expatriates, secondly the criticized and forgotten private health sector as a key player and thirdly the user and provider barriers faced by Omani patients in the Omani public health system.</p> <p>Conclusions</p> <p>The study has identified some of the challenges and barriers to TB control in Oman. These challenges are mainly related to unintended negative consequences arising from the current repatriation policy of immigrants and to and the lack of involvement of the private sector in TB control. TB control strategies designed to address these challenges are needed, for Oman to reach its TB elimination targets.</p

Estimates of Burden and Consequences of Infants Born Small for Gestational Age in Low and Middle Income Countries with INTERGROWTH-21(st) Standard: Analysis of CHERG Datasets.

Objectives To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21st birth weight standard. Design Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up. Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21st birth weight standard. Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level. With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. Setting CHERG birth cohorts from 14 population based sites in low and middle income countries. Main outcome measures In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. Results In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (\u3c2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). Conclusions In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countrie

Isolation and characterization of werneria chromene and dihydroxyacidissimol from burkillanthus malaccensis (Ridl.) swingle

The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthus malaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthus malaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacter baumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P. aeruginosa and P. putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of -8.1, -7.6, -7.0, and -7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthus malaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019