Viral diversity is considered a major impediment to the development of an effective HIV-1 vaccine. Despite this diversity, certain protein segments are nearly invariant across the known HIV-1 Group M sequences. We developed immunogens based on the highly conserved elements from the p24gag region according to two principles: the immunogen must (i) include strictly conserved elements of the virus that cannot mutate readily, and (ii) exclude both HIV regions capable of mutating without limiting virus viability, and also immunodominant epitopes located in variable regions. We engineered two HIV-1 p24gag DNA immunogens that express 7 highly Conserved Elements (CE) of 12–24 amino acids in length and differ by only 1 amino acid in each CE (‘toggle site’), together covering >99% of the HIV-1 Group M sequences. Altering intracellular trafficking of the immunogens changed protein localization, stability, and also the nature of elicited immune responses. Immunization of C57BL/6 mice with p55gag DNA induced poor, CD4+ mediated cellular responses, to only 2 of the 7 CE; in contrast, vaccination with p24CE DNA induced cross-clade reactive, robust T cell responses to 4 of the 7 CE. The responses were multifunctional and composed of both CD4+ and CD8+ T cells with mature cytotoxic phenotype. These findings provide a method to increase immune response to universally conserved Gag epitopes, using the p24CE immunogen. p24CE DNA vaccination induced humoral immune responses similar in magnitude to those induced by p55gag, which recognize the virus encoded p24gag protein. The inclusion of DNA immunogens composed of conserved elements is a promising vaccine strategy to induce broader immunity by CD4+ and CD8+ T cells to additional regions of Gag compared to vaccination with p55gag DNA, achieving maximal cross-clade reactive cellular and humoral responses.
The main objective of this study was to evaluate antidepressant activity of vanillin in mice models of depression.
Materials and Methods:
Animals were divided into five groups, consisting six mice in each group. Out of these, three groups served as control (distilled water, imipramine,and fluoxetine) and the remaining two groups received test drug in two different doses (10mg/kg and 100mg/kg). All the drugs were administered orally one hour before the test procedure for acute study and daily for ten days for chronic study. Mice were subjected to forced swim (FST) and tail suspension tests (TST).
Both the doses of vanillin reduced the immobility duration in TST as well as in FST. In TST, there was a statistically significant decrease in the immobility in all the groups when compared to the control (distilled water) group. But the reduction of immobility in FST did not show statistically significant reduction in immobility in the groups treated with vanillin when compared with control. In the chronic study group that received vanillin at a dose of 100mg/kg, the immobility reduction was significantly lower when compared to the group receiving fluoxetine.
Vanillin at the dosage of 100mg/kg has demonstrated antidepressant activity in mice, which is comparable with fluoxetine.
Antidepressant; depression; fluoxetine; imipramine; vanillin
Shadbindu Taila (ST) is an Ayurvedic formulation used as a remedy for loosening of tooth, weakness of the eyesight, loss of hair, diseases of head, etc., Present study is an attempt to develop some newer approaches for the quality control and standardization of ST. Standardized operating procedure for the preparation of ST was developed in accordance with Ayurvedic Formulary of India. Preliminary phytochemical, physicochemical, and chromatographic evaluation of ST was carried out. Safety of ST was evaluated in terms of skin irritation test and presence of heavy metals. Chemical characterization of ST was done on the basis of kaempferol using validated -High Performance Thin Layer Chromatographic (HPTLC) method. ST did not show presence of any of the heavy metals analyzed and was found non-irritant on rabbit skin. The quality control parameters resulted after scientific evaluation of ST can be used as reference standard for quality control/assurance laboratory of a pharmaceutical firm in order to have a proper quality check over its preparation and processing.
High performance thin layer chromatography; kaempferol; safety; Shadbindu Taila; standardization
Linguistic and genetic studies on Roma populations inhabited in Europe have unequivocally traced these populations to the Indian subcontinent. However, the exact parental population group and time of the out-of-India dispersal have remained disputed. In the absence of archaeological records and with only scanty historical documentation of the Roma, comparative linguistic studies were the first to identify their Indian origin. Recently, molecular studies on the basis of disease-causing mutations and haploid DNA markers (i.e. mtDNA and Y-chromosome) supported the linguistic view. The presence of Indian-specific Y-chromosome haplogroup H1a1a-M82 and mtDNA haplogroups M5a1, M18 and M35b among Roma has corroborated that their South Asian origins and later admixture with Near Eastern and European populations. However, previous studies have left unanswered questions about the exact parental population groups in South Asia. Here we present a detailed phylogeographical study of Y-chromosomal haplogroup H1a1a-M82 in a data set of more than 10,000 global samples to discern a more precise ancestral source of European Romani populations. The phylogeographical patterns and diversity estimates indicate an early origin of this haplogroup in the Indian subcontinent and its further expansion to other regions. Tellingly, the short tandem repeat (STR) based network of H1a1a-M82 lineages displayed the closest connection of Romani haplotypes with the traditional scheduled caste and scheduled tribe population groups of northwestern India.
Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between TH1 and TH2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.
We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).
The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r2>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 –0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ23 = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).
Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection.
Consumers demand high quality foods, which are fresh, tasty and nutritious; this has created considerable interest in the development of new food processing techniques. Presently, non-thermal techniques, including high hydrostatic pressure (HHP), are regarded with special interest by the food industry. Pressure ranges between 100 and 1200 MPa have been considered as effective to inactivate microorganisms including food-borne pathogens. HHP also improves rennet or acid coagulation of milk without any detrimental effect on flavour, body and texture and nutrients. Extended shelf-life and a “fresh-like” product presentation emphasize the need to take full account of food safety risks, alongside possible health benefits to consumers. These characteristics offer the dairy industry numerous practical applications to produce microbially safe and minimally processed dairy products with improved characteristics. Thus HHP is a powerful tool to develop novel dairy products of better nutritional and sensory quality, novel texture and increased shelf-life.
Dairy products; Hydrostatic pressure; Minimally processed; Cold processing
Background and Objectives
Despite India's substantial economic growth in the past two decades, girls in India are discriminated against in access to preventive healthcare including immunizations. Surprisingly, no study has assessed the contribution of gender based within-household discrimination to the overall inequality in immunization status of Indian children. This study therefore has two objectives: to estimate the gender based within-household inequality (GWHI) in immunization status of Indian children and to examine the inter-regional and inter-temporal variations in the GWHI.
Data and Methods
The present study used households with a pair of male-female siblings (aged 1–5 years) from two rounds of National Family Health Survey (NFHS, 1992–93 and 2005–06). The overall inequality in the immunization status (after controlling for age and birth order) of children was decomposed into within-households and between-households components using Mean log deviation to obtain the GWHI component. The analysis was conducted at the all-India level as well as for six specified geographical regions and at two time points (1992–93 and 2005–06). Household fixed-effects models for immunization status of children were also estimated.
Results and Conclusions
Findings from household fixed effects analysis indicated that the immunization scores of girls were significantly lower than that of boys. The inequality decompositions revealed that, at the all-India level, the absolute level of GWHI in immunization status decreased from 0.035 in 1992–93 to 0.023 in 2005–06. However, as a percentage of total inequality, it increased marginally (15.5% to 16.5%). In absolute terms, GWHI decreased in all the regions except in the North-East. But, as a percentage of total inequality it increased in the North-Eastern, Western and Southern regions. The main conclusions are the following: GWHI contributes substantially to the overall inequality in immunization status of Indian children; and though the overall inequality in immunization status declined in all the regions, the changes in GWHI were mixed.
Plasma is the most easily accessible source for biomarker discovery in clinical proteomics. However, identifying potential biomarkers from plasma is a challenge given the large dynamic range of proteins. The potential biomarkers in plasma are generally present at very low abundance levels and hence identification of these low abundance proteins necessitates the depletion of highly abundant proteins. Sample pre-fractionation using immuno-depletion of high abundance proteins using multi-affinity removal system (MARS) has been a popular method to deplete multiple high abundance proteins. However, depletion of these abundant proteins can result in concomitant removal of low abundant proteins. Although there are some reports suggesting the removal of non-targeted proteins, the predominant view is that number of such proteins is small. In this study, we identified proteins that are removed along with the targeted high abundant proteins. Three plasma samples were depleted using each of the three MARS (Hu-6, Hu-14 and Proteoprep 20) cartridges. The affinity bound fractions were subjected to gelC-MS using an LTQ-Orbitrap instrument. Using four database search algorithms including MassWiz (developed in house), we selected the peptides identified at <1% FDR. Peptides identified by at least two algorithms were selected for protein identification. After this rigorous bioinformatics analysis, we identified 101 proteins with high confidence. Thus, we believe that for biomarker discovery and proper quantitation of proteins, it might be better to study both bound and depleted fractions from any MARS depleted plasma sample.
References form the backbone of any medical literature. Presently, because of high inflation, it is very difficult for any library/organization/college to purchase all journals. The condition is even worse for an individual person, such as private practitioners. The solution lies in the free availability of full-text articles. Here, the authors share their experiences about the accessibility of free full-text articles.
Free full-text article; research work; access
Basal cell carcinoma (BCC) of the breast is a rare occurrence. To the best of our knowledge, only 34 cases of this rare malignancy have been reported worldwide. We report the case of a 48 year old lady who presented with history of rapid enlargement of a nevus over breast since three months. On initial examination a diagnosis of melanoma was considered. However the histopathology showed features suggestive of BCC. This case report highlights an atypical presentation of BCC.
Basal cell carcinoma; Melanoma; histopathology
Trigonella foenum-graecum (L.) (Fabaceae, Fenugreek) is an important ingredient of Ayurvedic and other marketed herbal formulations. Fenugreek seeds are employed in many traditional systems as an antibacterial and antidiabetic agent, gastric stimulant and galactogogue. Trigonelline, a major phytoconstituent found in fenugreek seeds, shows estrogenic, anti-diabetic and anti-invasive activity. Therefore, it is a suitable bioactive marker to establish the quality of crude drug and its formulations.
To develop an efficient and effective RP-HPLC method for estimation of trigonelline from Trigonella foenum-graecum seeds and its marketed herbal formulations.
Materials and Methods:
Separation and detection of trigonelline was carried out on a Cosmosil CN-MS column eluted with methanol:distilled water [95:5, v/v; pH 3.5 using hydrochloric acid]. Detection was carried out at 267 nm using a Photo Diode Array detector. Fenugreek seeds and two marketed herbal formulations were subjected for HPLC analysis of Trigonelline.
The RP-HPLC method was validated as per ICH guidelines and the content of trigonelline in marketed polyherbal formulations such as Dibet powder and Amyron syrup was determined. The LOD and LOQ were found to be 5.00 ng/mL and 50.00 ng/mL, respectively. Detector response was linear from 100.00 to 8000.00 ng/mL. The method was found to be simple, sensitive, accurate, reproducible and rugged.
This work can be recommended for quality assurance and marker-based standardization of formulations containing fenugreek seeds.
Amyron syrup; dibet powder; RP-HPLC; Trigonella foenum-graecum (L.); trigonelline
Transposon mutagenesis of Pseudomonas syringae Lz4W, a psychrophilic bacterium capable of growing at temperatures between 2 and 30°C, yielded 30 cold-sensitive mutants, and CSM1, one of these cold-sensitive mutants, was characterized. Growth of CSM1 was retarded when it was cultured at 4°C but not when it was cultured at 22°C and 28°C compared to the growth of wild-type cells, indicating that CSM1 is a cold-sensitive mutant of P. syringae Lz4W. The mutated gene in CSM1 was identified as trmE (coding for tRNA modification GTPase), and evidence is provided that this gene is induced at low temperatures. Further, the cold-inducible nature of the trmE promoter was demonstrated. In addition, the transcription start site and the various regulatory elements of the trmE promoter, such as the −10 region, −35 region, UP element, cold box, and DEAD box, were identified, and the importance of these regulatory elements in promoter activity were confirmed. The importance of trmE in rapid adaptation to growth at low temperatures was further highlighted by plasmid-mediated complementation that alleviated the cold-sensitive phenotype of CSM1.
Monilethrix is one of the hair shaft abnormalities with increased fragility of hair. Here we describe a ten-year-old girl with a history of hair loss and breakage of hair since three months of age, associated with keratosis pilaris along with an abnormal microscopic finding of a hair shaft. A cytogenetic study of the patient showed an unexpectedly high degree of Acrocentric association.
Acrocentric association; keratosis pilaris; monilethrix