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Role of sialoglycoproteins exclusively induced on host�s erythrocytes in Indian Visceral Leishmaniasis
No full textLeishmaniasis occurs in as many as 88 countries, (Figure. 1.2) with an approximate total population of 350 million people, most often in tropical and subtropical areas [WHO,
2010]. The geographical settings, where leishmaniasis occurs, range from Central and Couth American rain forests to West Asian deserts, with 90 percent of visceral
leishmaniasis cases occurring in India, Nepal, Bangladesh, Sudan, and Brazil. Other areas where Leishmaniasis is found range from Mexico, to Texas, from Northern Argentina, to
Southern Europe, from Asia, to The Middle East, and Africa [Chappuis et al., 2007].Although it is true that the distribution of Leishmania is limited by the habitats of the
sandfly vectors, human leishmaniasis continues to increase worldwid
Phenotypic and Genomic Characterization of Enterococcus Species from Some Nigerian Fermented Foods
No full textThe gram-positive Enterococci bacteria are generally used as a starter and probiotic cultures
in foods. However, they have emerged as one of the leading causes of nosocomial
infections worldwide, and this feature is aggravated by the development of antibiotic
resistance. Accurate identification of Enterococci at the species level is an important
task in food microbiology. In this study, 144 strains of Enterococcus species were isolated
from traditional fermented vegetable condiment and West African soft cheese
(wara) with the most predominant species being E. gallinarum (75%) followed by E. faecium
(14.5%), E. faecalis (7.6%), and E. casselliflavus (2.8%). The strains isolated were
characterized and identified using the polyphasic taxonomy approach. Phenotypically,
108 strains were characterized and identified to be E. gallinarum, 21 strains as E. faecium,
11 strains as E. faecalis, and 4 strains as E. casselliflavus. Thirty representative
strains were also subjected to genomic characterization, and the result obtained with
the phenotypic approach was confirmed. Therefore, the polyphasic taxonomy approach
was successful in the accurate identification of the Enterococcus species isolate
34 Cyo-EM visualization of Mycobacterium 70S ribosome reveals unique structural components at the function sites
No full textThe 3D structures of prokaryotic and eukaryotic ribosomes by crystallography and electron microscopy have revealed that they share an evolutionarily conserved core (Schmeing & Ramakrishnan, 2009), but each of the ribosomes contains its own set of specific proteins (or extensions of conserved proteins) and expansion segments of rRNAs (Melnikov et al., 2012). How these differences correlate to function still remains largely unknown. A 3D cryo-EM map of the 70S ribosome from Mycobacterium smegmatis (Msm70S) unveiled striking new structural features (Shasmal & Sengupta, 2012). The core of the Msm70S shows overall similarity with the core of the Escherichia coli 70S ribosome while containing additional mass in the periphery and solvent exposed sides. Some of the Mycobacterium ribosomal proteins are significantly bigger as compared to the E. coli counter parts. The rRNAs also contain extra helices, also revealed by their secondary structures. Most of the additional density of the Msm70S can be largely attributed to the extra helices present in the rRNAs, and extra domains of homologous proteins. One of the most notable features appears in the large subunit near L1 stalk as a structure forming a long helix with its upper end located in the vicinity of the mRNA exit channel (which we term the ‘steeple’). We propose that the prominent helical structure in mycobacterium 23S rRNA participates in modulating different steps of translation, especially the E site tRNA exit mechanism and propagation of mRNA 5′ en
Facile Synthesis of [1,2,3]-Triazole-Fused Isoindolines, Tetrahydroisoquinolines, Benzoazepines and Benzoazocines by Palladium-Copper Catalysed Heterocyclisation
No full textAn elegant method for the synthesis of 1,2,3-triazoles
fused with five-, six-, seven- and eight-membered benzoheterocycles, including isoindoline, tetrahydroisoquinoline, benzoazepine and benzoazocine, has been developed via palladium-copper catalysed reactions in one-pot. The broad scope of this reaction was illustrated
by effecting bis-heteroannulations, synthesis of uracil
derivatives of biological interest, and employment of acetylene gas as an inexpensive substrate. The reactions are experimentally simple and utilise easily accessible substrates of different type
Studies on Molecular Basis of Wilson Disease by Genetic and Functional Approaches
No full textWilson disease (WD), an inborn error of copper metabolism, is inherited in an autosomal recessive manner. It is caused due to mutations in ATP7B gene which impair the normal
function of the copper transporting P-type ATPase, resulting in copper accumulation and toxicity leading to hepatic and neuropsychiatric manifestations of WD. This study describes a comprehensive genetic analysis of 199 Indian WD patients including mutations detected
previously from this group, undertakes functional assessment of the nucleotide variants in ATP7B promoter, correlates genotype with disease phenotype and explores the effect of missense mutations on the molecular fate of the protein. The patient cohort harbors a total of 10 common and 48 rare mutations in the coding region of ATP7B including 22 novel changes. The common mutations represent 74% of characterized coding mutant alleles with
p.C271X (63/260) and p.G1101R (7/31) being the most prevalent in East and West Indian patients, respectively. The mutation spectrum between East and West is mostly different with only three mutations (p.G1061E, p.N1270S and p.A1049A-fs) being shared between both the groups. Eight novel and 10 reported variants have been detected in the promoter and non-coding regions (5'- and 3'-UTRs) of ATP7B. Promoter reporter assay demonstrated 5 variants and 1 haplotype to significantly downregulate promoter activity which might interfere with ATP7B gene regulation. The Neurological Involvement Score (NIS) was developed to capture the spectrum of neurological involvement in WD patients. By utilizing the age at onset, NIS and ATP7B mutational background of the patients, a genotype-phenotype
matrix was generated that could be effectively used to depict the phenotypic spectra of WD affected individuals and serve as a platform to identify prospective “outliers”
to be investigated for their remarkable phenotypic divergence. Next, study was conducted to ascertain the cellular localization and anterograde trafficking of GFP fusion constructs for 9 different ATP7B mutants in presence and absence of copper supplementation. While 6 of 9
mutants showed normal behavior, 2 mutants (p.G1061E and p.G1101R) were found to be mislocalized to endoplasmic reticulum and a single mutant (p.S1362A) was unresponsive to
copper induced redistribution suggesting that variant molecular phenotypes of ATP7B are likely to influence the clinical phenotype of WD patients. This effort is precursor to understanding the clinical heterogeneity of WD in the context of molecular events precipitated by the defects in the causal gene
Synthetic Studies of Benzannulated and Dibenzannulated OXA, AZA Heterocycles
No full textOver the past 30 years organometallic chemistry has changed dramatically the total scenario of organic synthesis. It has enriched and transformed chemical science to a degree and in ways that have few parallels in the history of the discipline. Synthetic applications facilitated by transition metal catalysts demonstrate the remarkable development of organometallics. Among all the organometallic compounds known, palladium derivatives have been most successfully adopted for the construction and decoration of various heterocyclic scaffolds,
exemplifying a conceptually different approach for heterocycle synthesis. The success of palladium catalyzed reactions for synthesizing heterocycles stems from the fact that they can construct complicated molecules from readily accessible starting materials under mild conditions and with high functional group compatibility. Furthermore, palladium tolerates a wide variety of functional groups, thus avoiding protection group chemistry and most
palladium-based methodologies proceeds stereo- and region-selectively offering excellent yields
Drug-resistant microorganisms with a higher fitness – can medicines boost pathogens?
No full textDrug-resistant microorganisms (DRMs) are generally thought to suffer from a fitness cost associated with their drugresistant trait, inflicting them a disadvantage when the drug pressure reduces. However, Leishmania resistant to
pentavalent antimonies shows traits of a higher fitness compared to its sensitive counterparts. This is likely due the combination of an intracellular pathogen and a drug that targets the parasite’s general defense mechanisms while
at the same time stimulating the host’s immune system, resulting in a DRM that is better adapted to withstand the
host’s immune response. This review aims to highlight how this fitter DRM has emerged and how it might affect the
control of leishmaniasis. However, this unprecedented example of fitter antimony-resistant Leishmania donovani is
also of significance for the control of other microorganisms, warranting more caution when applying or designing drugs that attack their general defense mechanisms or interact with the host’s immune system
Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway
No full textOne of the basic functions of insulin in the body is to inhibit lipolysis in adipocytes. Recently, we have found that insulin inhibits lipolysis and promotes triglyceride storage by decreasing transcription of adipose triglyceride lipase via the mTORC1-mediated pathway (P. Chakrabarti et al., Diabetes 59:775–781, 2010), although the mechanism of this effect remained unknown. Here, we used a genetic screen in Saccharomyces cerevisiae in order to identify a transcription factor that mediates the effect of Tor1 on
the expression of the ATGL ortholog in yeast. This factor, Msn4p, has homologues in mammalian cells that form a family of early growth response transcription factors. One member of the family, Egr1, is induced by insulin and nutrients and directly inhibits activity of the ATGL promoter in vitro and expression of ATGL in cultured adipocytes. Feeding animals a high-fat diet increases the activity of mTORC1 and the expression of Egr1 while decreasing ATGL levels in epididymal fat. We suggest that the evolutionarily
conserved mTORC1-Egr1-ATGL regulatory pathway represents an important component of the antilipolytic effect of
insulin in the mammalian organism
Immunofiltration assay for aflatoxin B1 based on the separation of pre-immune complexes
No full textA new approach for quantitative determination of AFB1 based on the separation of pre-immune complexes in the same immunoassay system has been developed. No additional step for the separation of pre-immune complexes is required. The method uses a test device for separation of pre-immune complexes from the free AFB1-enzyme conjugate by filtration through the membrane strips spotted with anti-AFB1 antibody. The bound enzyme conjugate was visualized
by super-catalyzed reporter deposition (Super-CARD) signal amplification method. The measured signal intensity is directly proportional to the amount of AFB1 present in the sample. The detection limit obtained by the present method was 15 pg/ml. The data on the analytical parameters
indicate that the newformat of AFB1 detection in foodstuffs is reproducible, accurate and specific. The method is user friendly and does not require any costly equipment or a well-equipped laborator
Puerarin, a selective oestrogen receptor modulator, disrupts pregnancy in rats at pre-implantation stage
No full textThe tubers of Pueraria tuberosa have folkloric repute as emmenagogue. The n-BuOH fraction of the ethanolic extract of tubers exhibits significant antifertility activity in laboratory animals. The present investigation explored the active principle(s) of the tuber extract with reference to contragestive effects in rats and probed the possible mechanism of action. Bioactivity-guided fractionation identified puerarin as the major constituent that exerted pregnancy-terminating effects. Oral administration of puerarin atR300 mg/kg per day for days (D) 1–2 post-coitus resulted in complete implantation failure. Serum oestradiol levels during D2–D5 and progesterone (P4) level on
D5 remained unaffected, but the endometrial expression of oestrogen receptor a (ERa) and ERb was adversely modulated that disrupted the implantation-specific characteristic endometrial oestrogenic milieu. The eventual consequence was loss of endometrial receptivity characterised by down-regulation of the uterine expression of P4 receptor (PR) and attenuation of endometrial expression of leukaemia
inhibitory factor, vascular endothelial growth factor and cyclo-oxygenase-2, the three important signalling molecules involved in the process of implantation. Light microscopic examination of the embryos demonstrated no untoward effect of puerarin on the development of embryos until D4, but D5 blastocysts underwent gross morphological distortion. The findings taken together are interpreted to suggest that puerarin adversely impacts the uterine expression of ER and PR that disrupts the implantation-conducive uterine milieu and prevents implantation. In conclusion, puerarin may be envisaged as a prospective molecule that merits further exploration for the development of non-steroidal post-coital contraceptive for women