IL10 Variant g.5311A Is Associated with Visceral Leishmaniasis in Indian Population

BackgroundVisceral leishmaniasis (VL) is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations.MethodologyAll the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India.

Result and Discussion

Our analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR) and rs3024498 (5311 A>G, 3’ UTR). Of these, a variant g.5311A is significantly associated with VL (χ²=18.87; p =0.00001). In silico approaches have shown that a putative micro RNA binding site (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL (‘A’ of rs3024498); and high frequency of leprosy (‘T’ of rs1554286), and Behcet’s (‘A’ of rs1518111) associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet’s disease. This study has potential implications in counseling and management of VL and other infectious diseases.     

Conserved water-mediated H-bonding dynamics of catalytic Asn 175 in plant thiol protease

The role of invariant water molecules in the activity of plant cysteine protease is ubiquitous in nature. On analysing the 11 different Protein DataBank (PDB) structures of plant thiol proteases, the two invariant water molecules W1 and W2 (W220 and W222 in the template 1PPN structure) were observed to form H-bonds with the O_b atom of Asn 175. Extensive energy minimization and molecular dynamics simulation studies up to 2 ns on all the PDB and solvated structures clearly revealed the involvement of the H-bonding association of the two water molecules in fixing the orientation of the asparagine residue of the catalytic triad. From this study, it is suggested that H-bonding of the water molecule at the W1 invariant site better stabilizes the Asn residue at the active site of the catalytic triad.     

Developmental Variation in Amylase Allozyme Activity Associated with Chromosome Inversions in DROSOPHILA PERSIMILIS

The amylase locus in Drosophila persimilis is polymorphic for allozymes, two of which show associations with naturally occurring chromosome 3 inversions. Amy1.09 occurs at high frequencies only in Whitney (WT), while the other common arrangements-Standard (ST), Klamath (KL) and Mendocino (MD)-are predominantly Amy 1.00. We have examined numerous strains, representing various electromorphs and inversions, for variation in cis-specific activity expression in both third-instar larvae and adults. Comparisons of these two life stages also allows the survey of developmental variation in amylase activities. The amount of activity variation exceeds electrophoretic variation at this locus. Moreover, this variation is largely nonrandom and reveals more genic divergence among inversions. The 1.00 allozyme of MD is more active than 1.00 KL in larvae and adults and shows a different developmental pattern. The activity of the 1.00 allozyme of KL is greater than 1.00 allozyme of ST in larvae and adults, but these two arrangements have similar developmental patterns. WT 1 with a 1.00 allele is dramatically different from the 1.00 allozymes of other arrangements in its developmental pattern. The 1.09 allozymes has high activity in WT and KL, but these arrangements differ in their developmental pattern of expression, WT being more active in adults. F2 segregational analyses are consistent with the variation being due to either structural enzyme variants or closely linked cis-acting regulatory elements. We argue that the suppression of recombination between arrangements has allowed the divergence in amylase activity among inversions.     

Murine splenocyte proliferation by porin of Shigella dysenteriae type 1 and inhibition of bacterial invasion of HeLa cell by anti-porin antibody

Abstract A highly sensitive nested polymerase chain reaction method was designed for the detection of a wide spectrum of strains from Borrelia burgdorferi sensu lato. This technique allows the detection of as little as 3 fg of total genomic DNA extracted and purified from pure cultures of the organism, this amount corresponds to less than 10 organisms. Two sets of primers homologous to conserved spots in the coding region of the hbb gene, encoding a conserved histone-like protein, were constructed. These were based on a multiple sequence alignment of 39 strains representing all the genomic groups described in B. burgdorferi sensu lato.     

Statistical optimization of growth media for Paecilomyces lilacinus 6029 using non-edible oil cakes

The development of biofriendly and economical alternatives to chemical pesticides is a globally important scientific challenge. In this work, Karanja-based media conditions were optimized for obtaining high production of biomass and spores of a biocontrol agent, the entomopathogenic fungus Paecilomyces lilacinus 6029, using a two-step statistical approach coupled with rigorous experimentation. In the first step, non-edible Karanja cake was screened out as a major substrate from other oil cakes. In the second step, biomass production was maximized by applying response surface methodology to experimental variations in key physico-chemical factors: carbon/nitrogen (C/N) ratio and pH. This approach eventually predicted a maximum biomass production of 10.559 g/l with a medium having a C/N ratio of 35.88 and pH 5.9. An experimental production of 10.529 g/l biomass was obtained. The remarkable agreement between the predicted and the experimentally obtained biomass confirm the validity of the approach utilized to maximize production of P. lilacinus.     

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.     

Mitochondrial haplogroup N1a phylogeography,with implication to the origin of European farmers

Background  

Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations.