The mycotoxin Citrinin was obtained from the fungus Penicillium citrinum. It was tested for it's Minimum Inhibitory Concentration (MIC) against some gram positive strains viz. Staphylococcus aureus, Bacillus pumilus, Bacillus subtillis, Bacillus cereus, Klebsiella pneumoniae, Streptococcus pneumoniae, Lactobacillus arabinosus and gram negative strains E.Coli, Shigella dysenteriae, shigella sonnei, shigella boydii, Salmonella typhimurium, Proteus mirabilis and Vibrio cholerae. Further the zones of inhibition produced by the fungal extract against the bacterial strains were assayed and compared with those produced by the standard antibiotic ciprofloxacin.

Various pharmacognostic parameters including macroscopy, microscopy, chemomicroscopy and behaviour of powdered drug on treatment with different chemical reagents were studied on the leaves of Bauhinia purpurea Linn. (Family Caesalpinaceae). Phytochemical screening of the plant part with various solvents revealed the presence of phenolic compounds, tannins, flavonoids, phytosterols, saponins and glycosides in it.

Background:

The global health impact and disease burden due to chronic arsenic toxicity has not been well studied in West Bengal.

Objective:

To ascertain these, a scientific epidemiological study was carried out in a district of the state.

Materials and Methods:

Epidemiological study was carried out by house-to-house survey of arsenic affected villages in the district of Nadia. A stratified multi-stage design has been adopted for this survey for the selection of the participants. A total number of 2297 households of 37 arsenic affected villages in all the 17 blocks were surveyed in the district.

Result:

Out of 10469 participants examined, prevalence rate of arsenicosis was found to be 15.43%. Out of 0.84 million people suspected to be exposed to arsenic, 0.14 million people are estimated to be suffering from arsenicosis in the district. Highest level of arsenic in drinking water sources was found to be 1362 μg/l, and in 23% cases it was above 100 μg/l. Majority of the population living in the arsenic affected villages were of low socio-economic condition, inadequate education and were farmers or doing physical labour. Chronic lung disease was found in 207 (12.81%) subjects among cases and 69 (0.78%) in controls. Peripheral neuropathy was found in 257 (15.9%) cases and 136 (1.5%) controls.

Conclusion:

Large number of people in the district of Nadia are showing arsenical skin lesion. However, insufficient education, poverty, lack of awareness and ineffective health care support are major factors causing immense plight to severely arsenic affected people.

The anthelmintic activity of the Imethanolic extract of the root bark of Carissa carandas was evaluated on adult Indian earthworm (Pheretima posthuma) using albendazole as a reference standard. The extract caused paralysis followed by the death of worm at the tested dose level. The extract at the highest tested concentration has anthelmintic activity comparable with that of standard drug albendazole.

The microscopic and macroscopic characters of the rhizome of Curcuma domestica Val. were studied. The behavior of the powdered drug in the presence of various chemicals was also studied. Preliminary phytochemical screening on the various extracts of the rhizome was done in order to ascertain the various chemical constituents present. These studies were carried out to identify this plant for future research work.

The leaves and seeds of Cassia tora (Family Caesalpinaceae) are used in the treatment of leprosy, ring worm, flatulence, colic, dyspepsia, constipation, cough, bronchitis and cardiac disorders in the Ayurvedic systems of medicine. The present study deals with the study of macroscopic characters of the leaves, ash values, extractive values, behavior on treatment with different chemical reagents and fluorescence characters under ultraviolet light. Preliminary phytochemical studies on different extractives of the leaves were also performed. These studies will help in the identification of the plant for further research.

The methanolic extract of leaves of Mesua ferrea Linn. were tested for its antibacterial potentiality against 103 various strains of bacteria including Staphylococcus aureus, Bacillus spps. Klebsiella spps., Streptococus pneumoniae, Sarcina lutea, Lactobacilus arabinosus, Escherichia coli, shigellae, salmonellae, Proteus spps., Pseudomonas spps. and the vibrios. Significant antibacterial effects were produced by the extract against Staphylococcus aureus, Bacillus sppa., lactobacilli, Escherichia coli, shigellae and salmonellae and the results were compared with standard antibiotic ciprofloxacin. Further the extract was proved to be bacterial in its action.

The benzene extract of the leaves of Lagerstroemia paviflora Roxb was tested for its Minimum Inhibitory Concentration (MIC) against Gram Positive Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Klebsiella pneumoniae, Streptococcus pneumoniae, Lactobacillus arabinosus and gram negative strains E.Coli, Shigella dysenteriae, shigella sonnei, shigella boydii, Salmonella typhimurium, Proteus mirabilis and Vibrio cholerae. Further the zones of inhibition Produced by the crude extract against four selected bacterial strains were measured and compared with those produced by the standard antibiotic Ciprofloxacin against the same bacterial strains.

The methanolic extract of the leaf-stalk of curcuma longa LINN, was tested for its minimum Inhibitor concentration (MIC) against Gram positive-staphylococcus aureus, Bacillus pumilus, Bacillus subtilis, klebsiella pnemoniae, bacillus cereus, streptococcus pneumoniae, Lactobacillus arabinosus and gram negative E.coli, shigella dysenteriae, shigella sonnei, shigella boydii, salmonella typhimurium, proteus mirabilis, and Vibrio cholerae strains, further, the ones of inhibition produced by the crude extract against four selected bacterial strains were measured and compared with those produced by the standard antibiotic ciprofloxacin against the same bacterial strains.

The cysteine biosynthetic pathway is essential for survival of the protist pathogen Entamoeba histolytica, and functions by producing cysteine for countering oxidative attack during infection in human hosts. Serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS) are involved in cysteine biosynthesis and are present in three isoforms each. While EhSAT1 and EhSAT2 are feedback inhibited by end product cysteine, EhSAT3 is nearly insensitive to such inhibition. The active site residues of EhSAT1 and of EhSAT3 are identical except for position 208, which is a histidine residue in EhSAT1 and a serine residue in EhSAT3. A combination of comparative modeling, multiple molecular dynamics simulations and free energy calculation studies showed a difference in binding energies of native EhSAT3 and of a S208H-EhSAT3 mutant for cysteine. Mutants have also been generated in vitro, replacing serine with histidine at position 208 in EhSAT3 and replacing histidine 208 with serine in EhSAT1. These mutants showed decreased affinity for substrate serine, as indicated by Km, compared to the native enzymes. Inhibition kinetics in the presence of physiological concentrations of serine show that IC50 of EhSAT1 increases by about 18 folds from 9.59 µM for native to 169.88 µM for H208S-EhSAT1 mutant. Similar measurements with EhSAT3 confirm it to be insensitive to cysteine inhibition while its mutant (S208H-EhSAT3) shows a gain of cysteine inhibition by 36% and the IC50 of 3.5 mM. Histidine 208 appears to be one of the important residues that distinguish the serine substrate from the cysteine inhibitor.

This paper presents new estimates of sibling correlations in health and socioeconomic outcomes over the life course in the U.S. Sibling correlations provide an omnibus measure of the importance of all family and community influences. I find that sibling correlations in a range of health and socioeconomic outcomes start quite high at birth and remain high over the life course. The sibling correlation in birth weight is estimated to be 0.5. Sibling correlations in test scores during childhood are as high as 0.6. Sibling correlations in adult men’s wages are also around 0.5. Decompositions provide suggestive evidence on which pathways may account for the gradients in health and SES by family background. For example, sibling correlations in cognitive skills and non-cognitive skills during childhood are lower controlling for family income. Similarly, parent education levels can account for a sizable portion of the correlation in adult health status among brothers.

The attitudes of medical students toward the current United States healthcare system are not well described in the literature. A graded survey was developed to assess awareness and motivation toward the care of the uninsured and underinsured as well as the impact of a video intervention on these attitudes. The survey, which showed good internal consistency (Cronbach’s alpha = 0.85), was administered before and after viewing a collection of videotaped patient stories. Although a spectrum of beliefs emerged from the analysis of survey responses, some common attitudes were identified. Eighty-five percent of respondents either agreed or strongly agreed that medical care should be provided to everyone, regardless of their ability to pay. In addition, 66% indicated they would be willing to forgo a portion of their income to provide care to those who do not have access to healthcare services. These values were strongly correlated with increasing respondent age and primary care specialty choice (p<0.01). The video intervention did not heavily influence student responses, perhaps due to a ceiling effect created by the large number of students who were already sympathetic toward the underserved. Overall, this data reflects that United States medical students recognize a need to provide care to the underserved and are willing to make personal sacrifices to meet that need.

Prosthesis loosening, associated with wear-particle–induced inflammation and osteoclast-mediated bone destruction, is a common cause for joint implant failure, leading to revision surgery. Adenosine A2A receptors (A2AR) mediate potent anti-inflammatory effects in many tissues and prevent osteoclast differentiation. We tested the hypothesis that an A2AR agonist could reduce osteoclast-mediated bone resorption in a murine calvaria model of wear-particle–induced bone resorption. C57Bl/6 and A2A knockout (A2ARKO) mice received ultrahigh-molecular weight polyethylene particles (UHMWPE) and were treated daily with either saline or the A2AR agonist CGS21680. After 2 weeks, micro-computed tomography of calvaria demonstrated that CGS21680 reduced particle-induced bone pitting and porosity in a dose-dependent manner, increasing cortical bone and bone volume compared to control mice. Histological examination demonstrated diminished inflammation after treatment with CGS21680. In A2AKO mice, CGS21680 did not affect osteoclast-mediated bone resorption or inflammation. Levels of bone-resorption markers receptor activator of nuclear factor-kB (RANK), RANK ligand (RANKL), cathepsin K, CD163, and osteopontin were reduced following CGS21680 treatment, together with a reduction in osteoclasts. Secretion of interleukin 1β (IL-1β) and TNFα was significantly decreased, whereas IL-10 was markedly increased in bone by CGS21680. These results in mice suggest that site-specific delivery of an adenosine A2AR agonist could enhance implant survival, delaying or eliminating the need for revision arthroplastic surgery.

The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration’s (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org), as well as related events of interest.

The aim of this study was to prepare nanostructured lipid carriers (NLC)-based topical gel of aceclofenac for the treatment of inflammation and allied conditions. Stearic acid as the solid lipid, oleic acid as the liquid lipid, pluronic F68 as the surfactant, and phospholipon 90G as the co-surfactant were used. NLCs were prepared by melt-emulsification, low-temperature solidification, and high-speed homogenization methods. Characterization of the NLC dispersion was carried out through particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and an in vitro release study. The anti-inflammatory effect of the NLC gel was assessed by the rat paw edema technique and compared to marketed aceclofenac gel. The NLC dispersions exhibited d90% between 233 nm and 286 nm. All of the NLC showed high entrapment efficiency ranging from 67% to 82%. The particle size of NLC was further confirmed by the SEM study. The result of DSC showed that aceclofenac was dispersed in NLC in an amorphous state. Both the entrapment and release rate were affected by the percentage of oleic acid, but the method of preparation affected only the entrapment efficiency. The nanoparticulate dispersion was suitably gelled and assessed for in vitro permeation. Finally, NLC-based gels were found to possess superior (almost double) the anti-inflammatory activity compared to the marketed product. The anti-inflammatory activity of NLC gel showed a rapid onset of action, as well as a prolonged duration of action as compared with the marketed gel.

The SLIT2-ROBO1/2 pathways control diverse biological processes, including growth regulation. To understand the role of SLIT2 and ROBO1/2 in cervical carcinogenesis, firstly their RNA expression profiles were screened in 21 primary uterine cervical carcinoma (CACX) samples and two CACX cell lines. Highly reduced expressions of these genes were evident. Concomitant alterations [deletion/methylation] of the genes were then analyzed in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN, SLIT2 was deleted in 22% samples compared to 9% for ROBO1 and none for ROBO2, whereas comparable methylation was observed for both SLIT2 (30%) and ROBO1 (22%) followed by ROBO2 (9%). In CACX, alteration of the genes were in the following order: Deletion: ROBO1 (48%) > SLIT2 (35%) > ROBO2 (33%), Methylation: SLIT2 (34%) > ROBO1 (29%) > ROBO2 (26%). Overall alterations of SLIT2 and/or ROBO1 (44%) and SLIT2 and/or ROBO2 (39%) were high in CIN followed by significant increase in stage I/II tumors, suggesting deregulation of these interactions in premalignant lesions and early invasive tumors. Immunohistochemical analysis of SLIT2 and ROBO1/2 in CACX also showed reduced expression concordant with molecular alterations. Alteration of all these genes predicted poor patient outcome. Multiparous (≥5) women with altered SLIT2 and ROBO1 along with advanced tumor stage (III/IV) and early sexual debut (<19 years) had worst prognosis. Our data suggests the importance of abrogation of SLIT2-ROBO1 and SLIT2-ROBO2 interactions in the initiation and progression of CACX and also for early diagnosis and prognosis of the disease.

N-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins from proteases. The N-linked glycans attach to asparagines in the sequence context Asn-X-Ser/Thr, where X is any amino acid except proline. Any variation (e.g. non-synonymous single nucleotide polymorphism or mutation) that abolishes the N-glycosylation sequence motif will lead to the loss of a glycosylation site. On the other hand, variations causing a substitution that creates a new N-glycosylation sequence motif can result in the gain of glycosylation. Although the general importance of glycosylation is well known and acknowledged, the effect of variation on the actual glycoproteome of an organism is still mostly unknown. In this study, we focus on a comprehensive analysis of non-synonymous single nucleotide variations (nsSNV) that lead to either loss or gain of the N-glycosylation motif. We find that 1091 proteins have modified N-glycosylation sequons due to nsSNVs in the genome. Based on analysis of proteins that have a solved 3D structure at the site of variation, we find that 48% of the variations that lead to changes in glycosylation sites occur at the loop and bend regions of the proteins. Pathway and function enrichment analysis show that a significant number of proteins that gained or lost the glycosylation motif are involved in kinase activity, immune response, and blood coagulation. A structure-function analysis of a blood coagulation protein, antithrombin III and a protease, cathepsin D, showcases how a comprehensive study followed by structural analysis can help better understand the functional impact of the nsSNVs.

Protein syntheses mediated by cellular and viral internal ribosome entry sites (IRESs) are believed to have many features in common. Distinct mechanisms for ribosome recruitment and preinitiation complex assembly between the two processes have not been identified thus far. Here we show that the methylation status of rRNA differentially influenced the mechanism of 80S complex formation on IRES elements from the cellular sodium-coupled neutral amino acid transporter 2 (SNAT2) versus the hepatitis C virus mRNA. Translation initiation involves the assembly of the 48S preinitiation complex, followed by joining of the 60S ribosomal subunit and formation of the 80S complex. Abrogation of rRNA methylation did not affect the 48S complex but resulted in impairment of 80S complex assembly on the cellular, but not the viral, IRESs tested. Impairment of 80S complex assembly on the amino acid transporter SNAT2 IRES was rescued by purified 60S subunits containing fully methylated rRNA. We found that rRNA methylation did not affect the activity of any of the viral IRESs tested but affected the activity of numerous cellular IRESs. This work reveals a novel mechanism operating on a cohort of cellular IRESs that involves rRNA methylation for proper 80S complex assembly and efficient translation initiation.

Motivation: Identifier (ID) mapping establishes links between various biological databases and is an essential first step for molecular data integration and functional annotation. ID mapping allows diverse molecular data on genes and proteins to be combined and mapped to functional pathways and ontologies. We have developed comprehensive protein-centric ID mapping services providing mappings for 90 IDs derived from databases on genes, proteins, pathways, diseases, structures, protein families, protein interaction, literature, ontologies, etc. The services are widely used and have been regularly updated since 2006.

Availability: www.uniprot.org/mappingandproteininformation-resource.org/pirwww/search/idmapping.shtml

Contact: huang@dbi.udel.edu

Background

Proteins destined to be Glycosylphosphatidylinositol (GPI) anchored are translocated into the ER lumen completely before the C-terminal GPI anchor attachment signal sequence (SS) is removed by the GPI-transamidase and replaced by a pre-formed GPI anchor precursor. Does the SS have a role in dictating the conformation and function of the protein as well?

Methodology/Principal Findings

We generated two variants of the Als5 protein without and with the SS in order to address the above question. Using a combination of biochemical and biophysical techniques, we show that in the case of Als5, an adhesin of C. albicans, the C-terminal deletion of 20 amino acids (SS) results in a significant alteration in conformation and function of the mature protein.

Conclusions/Significance

We propose that the locking of the conformation of the precursor protein in an alternate conformation from that of the mature protein is one probable strategy employed by the cell to control the behaviour and function of proteins intended to be GPI anchored during their transit through the ER.

Constitutive STAT signaling provides growth promoting signals in many forms of malignancy. We performed molecular modeling and molecular dynamics studies of the interaction between the regulatory Src homology 2 (SH2) domains of STAT3 and 6 with phosphorylated peptides of the herpesviral oncoprotein Tip, which facilitates Src kinase mediated STAT-activation and T cell proliferation. The studies give insight into the ligand binding specificity of the STAT SH2 domains and provide the first model for the differential activation of STAT3 or STAT6 by two distinct regions of the viral Tip protein. The biological relevance of the modeled interactions was then confirmed by activation studies using corresponding recombinant oncoproteins, and finally by respective recombinant viruses. The functional data give experimental validation of the molecular dynamics study, and provide evidence for the involvement of STAT6 in the herpesvirus induced T cell proliferation.

Background

Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo.

Methods/Design

The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrolment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation.

Discussion

The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.

Trial Registration

Ghana: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000582055; India: CLINICALTRIALS.GOV - NCT01138449; Tanzania: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055.