Socioeconomic and cultural differentials in age at marriage and the effect on fertility in Nepal

Age at marriage is one of the factors that influence the fertility behaviour of women, particularly in a society like Nepal where contraceptive use is low. Socioeconomic and cultural factors, particularly religion and ethnicity, are important variables in determining age at marriage in Nepal. Fertility was negatively related with age at marriage. Marriage duration had a greater influence on fertility than age at marriage, although these were strongly correlated.     

Biodegradable and biocompatible multi-arm star amphiphilic block copolymer as a carrier for hydrophobic drug delivery

Multi-arm star amphiphilic block copolymers (SABCs) with approximately 32 arms were synthesized and characterized for drug delivery applications. A hyperbranched polyester, boltorn^® H40 (H40), was used as the macroinitiator for the ring-opening polymerization of ?-caprolactone (?-CL). The resulting multi-arm H40-poly(?-caprolactone) (H40-PCL-OH) was further reacted with carboxyl terminated methoxy poly(ethylene glycol) (MPEG-COOH) to form H40-PCL-b-MPEG copolymers. The resulting SABCs were characterized by ¹H NMR spectroscopy and gel permeation chromatography (GPC). The critical aggregation concentration (CAC) of H40-PCL-b-MPEG was 3.8 mg/L as determined by fluorescence spectrophotometry. Below the CAC, stable unimolecular micelles were formed with an average diameter of 18 nm as measured by TEM. Above the CAC, unimolecular micelles exhibited agglomeration with an average diameter of 98 nm. The hydrodynamic diameter of these agglomerates was found to be 122 nm, as measured by dynamic light scattering (DLS). The drug loading efficacy of the H40-PCL-b-MPEG micelles was 26 wt%. Drug release study showed an initial burst followed by a sustained release of the entrapped hydrophobic model drug, 5-fluorouracil, over a period of 9–140 h. These results indicate that the H40-PCL-b-MPEG micelles have great potential as hydrophobic drug delivery carriers.     

Identification of a Novel Protein Binding Motif within the T-synthase for the Molecular Chaperone Cosmc

Prior studies suggested that the core 1 β3-galactosyltransferase (T-synthase) is a specific client of the endoplasmic reticulum chaperone Cosmc, whose function is required for T-synthase folding, activity, and consequent synthesis of normal O-glycans in all vertebrate cells. To explore whether the T-synthase encodes a specific recognition motif for Cosmc, we used deletion mutagenesis to identify a cryptic linear and relatively hydrophobic peptide in the N-terminal stem region of the T-synthase that is essential for binding to Cosmc (Cosmc binding region within T-synthase, or CBRT). Using this sequence information, we synthesized a peptide containing CBRT and found that it directly interacts with Cosmc and also inhibits Cosmc-assisted in vitro refolding of denatured T-synthase. Moreover, engineered T-synthase carrying mutations within CBRT exhibited diminished binding to Cosmc that resulted in the formation of inactive T-synthase. To confirm the general recognition of CBRT by Cosmc, we performed a domain swap experiment in which we inserted the stem region of the T-synthase into the human β4GalT1 and found that the CBRT element can confer Cosmc binding onto the β4GalT1 chimera. Thus, CBRT is a unique recognition motif for Cosmc to promote its regulation and formation of active T-synthase and represents the first sequence-specific chaperone recognition system in the ER/Golgi required for normal protein O-glycosylation.     

Acceptor specificities and selective inhibition of recombinant human Gal- and GlcNAc-transferases that synthesize core structures 1, 2, 3 and 4 of O-glycans

Background

Modifications of proteins by O-glycosylation determine many of the properties and functions of proteins. We wish to understand the mechanisms of O-glycosylation and develop inhibitors that could affect glycoprotein functions and alter cellular behavior.

Methods

We expressed recombinant soluble human Gal- and GlcNAc-transferases that synthesize the O-glycan cores 1 to 4 and are critical for the overall structures of O-glycans. We determined the properties and substrate specificities of these enzymes using synthetic acceptor substrate analogs. Compounds that were inactive as substrates were tested as inhibitors.

Results

Enzymes significantly differed in their recognition of the sugar moieties and aglycone groups of substrates. Core 1 synthase was active with glycopeptide substrates but GlcNAc-transferases preferred substrates with hydrophobic aglycone groups. Chemical modifications of the acceptors shed light on enzyme–substrate interactions. Core 1 synthase was weakly inhibited by its substrate analog benzyl 2-butanamido-2-deoxy-α-d-galactoside while two of the three GlcNAc-transferases were selectively and potently inhibited by bis-imidazolium salts which are not substrate analogs.

Conclusions

This work delineates the distinct specificities and properties of the enzymes that synthesize the common O-glycan core structures 1 to 4. New inhibitors were found that could selectively inhibit the synthesis of cores 1, 2 and 3 but not core 4.

General significance

These studies help our understanding of the mechanisms of action of enzymes critical for O-glycosylation. The results may be useful for the re-engineering of O-glycosylation to determine the roles of O-glycans and the enzymes critical for O-glycosylation, and for biotechnology with potential therapeutic applications.     

Knowledge,Attitude and Practice Regarding Dengue Fever among the Healthy Population of Highland and Lowland Communities in Central Nepal

Background

Dengue fever (DF) is the most rapidly spreading mosquito-borne viral disease in the world. In this decade it has expanded to new countries and from urban to rural areas. Nepal was regarded DF free until 2004. Since then dengue virus (DENV) has rapidly expanded its range even in mountain regions of Nepal, and major outbreaks occurred in 2006 and 2010. However, no data on the local knowledge, attitude and practice (KAP) of DF in Nepal exist although such information is required for prevention and control measures.

Methods

We conducted a community based cross-sectional survey in five districts of central Nepal between September 2011 and February 2012. We collected information on the socio-demographic characteristics of the participants and their knowledge, attitude and practice regarding DF using a structured questionnaire. We then statistically compared highland and lowland communities to identify possible causes of observed differences.

Principal Findings

Out of 589 individuals interviewed, 77% had heard of DF. Only 12% of the sample had good knowledge of DF. Those living in the lowlands were five times more likely to possess good knowledge than highlanders (P<0.001). Despite low knowledge levels, 83% of the people had good attitude and 37% reported good practice. We found a significantly positive correlation among knowledge, attitude and practice (P<0.001). Among the socio-demographic variables, the education level of the participants was an independent predictor of practice level (P<0.05), and education level and interaction between the sex and age group of the participants were independent predictors of attitude level (P<0.05).

Conclusion

Despite the rapid expansion of DENV in Nepal, the knowledge of people about DF was very low. Therefore, massive awareness programmes are urgently required to protect the health of people from DF and to limit its further spread in this country.     

DIPOS: database of interacting proteins in Oryza sativa

Rice is an important crop throughout the world and is the staple food for about half the world's population. For better breeding and improved production, we need to know the function of rice molecules which facilitate their function through interactions with each other. The database of interacting proteins in Oryza sativa (DIPOS) provides comprehensive information of interacting proteins in rice, where the interactions are predicted using two computational methods, i.e., interologs and domain based methods. DIPOS contains 14?614?067 pairwise interactions among 27?746 proteins, covering about 41% of the whole Oryaza sativa proteome. Furthermore, each interaction is assigned a confidence score which further enables biologists to sort out the important proteins. Biological explanations of pathways and interactions are also provided based on the database. Public access to the DIPOS is available at and .     

Establishing a health demographic surveillance site in Bhaktapur district, Nepal: initial experiences and findings

ABSTRACT: BACKGROUND: A health demographic surveillance site (HDSS) provides longitudinal data regarding health and demography in countries with coverage error and poor quality data on vital registration systems due to lack of public awareness, inadequate legal basis and limited use of data in health planning. The health system in Nepal, a low-income country, does not focus primarily on health registration, and does not conduct regular health data collection. This study aimed to initiate and establish the first HDSS in Nepal. RESULTS: We conducted a baseline survey in Jhaukhel and Duwakot, two villages in Bhaktapur district. The study surveyed 2,712 households comprising a total population of 13,669. The sex ratio in the study area was 101 males per 100 females and the average household size was 5. The crude birth and death rates were 9.7 and 3.9/1,000 population/year, respectively. About 11% of births occurred at home, and we found no mortality in infants and children less than 5 years of age. Various health problems were found commonly and some of them include respiratory problems (41.9%); headache, vertigo and dizziness (16.7%); bone and joint pain (14.4%); gastrointestinal problems (13.9%); heart disease, including hypertension (8.8%); accidents and injuries (2.9%); and diabetes mellitus (2.6%). The prevalence of non-communicable disease (NCD) was 4.3% (95% CI: 3.83; 4.86) among individuals older than 30 years. Age-adjusted odds ratios showed that risk factors, such as sex, ethnic group, occupation and education, associated with NCD. CONCLUSION: Our baseline survey demonstrated that it is possible to collect accurate and reliable data in a village setting in Nepal, and this study successfully established an HDSS site. We determined that both maternal and child health are better in the surveillance site compared to the entire country. Risk factors associated with NCDs dominated morbidity and mortality patterns.     

A proteomic approach to identification of plutonium-binding proteins in mammalian cells

Plutonium can enter the body through different routes and remains there for decades; however its specific biochemical interactions are poorly defined. We, for the first time, have studied plutonium-binding proteins using a metalloproteomic approach with rat PC12 cells. A combination of immobilized metal ion chromatography, 2D gel electrophoresis, and mass spectrometry was employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu⁴⁺-NTA (plutonium bound to nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were identified. In contrast to the previously known plutonium-binding proteins transferrin and ferritin, which bind ferric ions, most identified proteins in our experiment are known to bind calcium, magnesium, or divalent transition metal ions. The identified plutonium interacting proteins also have functional roles in downregulation of apoptosis and other pro-proliferative processes. MetaCore™ analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.     

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal

Background

Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal.

Methods

We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls.

Results

We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42–8.61, p?<?0.001 and OR: 3.7, 95% CI 2.35–5.92, p?<?0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02–51.04, p?=?0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified.

Conclusions

HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu.

     

Isolation and molecular characterization of five entomopathogenic nematode species and their bacterial symbionts from eastern Australia

BioControl - Entomopathogenic nematodes (EPNs) are used in biological control of pest insects but their potential may be limited by strain availability from different bioregions and effectiveness...