1- and 2-substituted naphthalenes: a new class of potential hypotensive agents

A series of 2-substituted aminomethyloxy naphthalenes 1 and 4-(1-naphthoxy-2-substituted aminomethyl)-butanoic acids 2 were synthesized by Mannich reaction of 4-(2-naphthoxy)-butanoic acid 3 and 4-(1-naphthoxy)-butanoic acid 4 with appropriate secondary amines and para-formaldehyde. The newly synthesized compounds were tested for their hypotensive activity at 5 mg/kg i.v. dose in cats. The results indicated that the analogue 2-(N4-phenyl-N1-piperazino)-methyloxy naphthalene 1d (> N = N4-phenyl-N1-piperazino) was the most active analogue when its hypotensive activity was compared to the reference compound propranolol.     

A Web-Based Platform for Designing Vaccines against Existing and Emerging Strains of Mycobacterium tuberculosis

Development of an effective vaccine against drug-resistant Mycobacterium tuberculosis (Mtb) is crucial for saving millions of premature deaths every year due to tuberculosis. This paper describes a web portal developed for assisting researchers in designing vaccines against emerging Mtb strains using traditional and modern approaches. Firstly, we annotated 59 genomes of Mycobacterium species to understand similarity/dissimilarity between tuberculoid, non-tuberculoid and vaccine strains at genome level. Secondly, antigen-based vaccine candidates have been predicted in each Mtb strain. Thirdly, epitopes-based vaccine candidates were predicted/discovered in above antigen-based vaccine candidates that can stimulate all arms of immune system. Finally, a database of predicted vaccine candidates at epitopes as well at antigen level has been developed for above strains. In order to design vaccine against a newly sequenced genome of Mtb strain, server integrates three modules for identification of strain-, antigen-, epitope-specific vaccine candidates. We observed that 103522 unique peptides (9mers) had the potential to induce an antibody response and/or promiscuous binder to MHC alleles and/or have the capability to stimulate T lymphocytes. In summary, this web-portal will be useful for researchers working on designing vaccines against Mtb including drug-resistant strains. Availability: The database is available freely at http://crdd.osdd.net/raghava/mtbveb/.     

The effect of clove and cinnamon oils on growth of and aflatoxin production by Aspergillus flavus

The effect of different concentrations of clove and cinnamon oils was studied on the growth of and aflatoxin production by Aspergillus flavus in SMKY liquid medium. The effect of these compounds was also verified against aflatoxin production in maize. Significant reduction (P < 0.05) in the elaboration of aflatoxin in liquid culture after treatment with more than 100 μg ml^-1 of these compounds was recorded. Cinnamon oil exhibited maximum inhibitory action and reduced 78% aflatoxin formation on maize at 1000 mg kg^-1.     

Prediction of nuclear proteins using SVM and HMM models

Background  

The nucleus, a highly organized organelle, plays important role in cellular homeostasis. The nuclear proteins are crucial for chromosomal maintenance/segregation, gene expression, RNA processing/export, and many other processes. Several methods have been developed for predicting the nuclear proteins in the past. The aim of the present study is to develop a new method for predicting nuclear proteins with higher accuracy.     

Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL)

Background

Post kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis, caused by Leishmania donovani, constitutes an important reservoir for the parasite. Parallel functioning of counter acting immune responses (Th1/Th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis.

Methodology/Principal Findings

In the present study, human cytokine/chemokine/receptor specific cDNA array technique was employed to identify modulations in gene expression of host immuno-determinants during PKDL, followed by evaluation of Th17 type responses by analyzing mRNA and protein expression of Th17 markers (IL-23, IL-17, RORγt) and performing functional assays using Leishmania antigen (TSLA) or recombinant (rec)IL-17. Array analysis identified key immuno-regulatory molecules including cytokines (TNF-α, IFN-γ, IL-10, IL-17), chemokines (MCP-1, MIP-1α), apoptotic molecules (FasL, TRAIL, IRF-1) and receptors (CD40, Fas). Up regulation in lesional expression of Th17 markers was observed during PKDL compared to control (IL-17 and IL-23, P = 0.0008; RORγt, P = 0.02). In follow-up samples, chemotherapy significantly down regulated expression of all markers. In addition, lesional expression of IL-17 was confirmed at protein level by Immuno-histochemistry. Further, systemic presence of Th17 responses (IL-17 and IL-23) was observed in plasma samples from PKDL patients. In functional assays, TSLA stimulated the secretion of IL-17 and IL-23 from PBMCs of PKDL patients, while recIL-17 enhanced the production of TNF-α as well as nitric oxide (NO) in PKDL compared to control (TNF-α, P = 0.0002; NO, P = 0.0013). Further, a positive correlation was evident between lesional mRNA expression of IL-17 and TNF-α during PKDL.

Conclusion/Significance

The results highlight key immune modulators in PKDL and provide evidence for the involvement of Th17 type responses in the disease pathogenesis.     

Genome sequence of the marine bacterium Marinilabilia salmonicolor JCM 21150T

We report the 4.98-Mb genome sequence of Marinilabilia salmonicolor JCM 21150(T), which was isolated from marine mud in the year 1961. The draft genome of strain Marinilabilia salmonicolor JCM 21150(T) contains 4,982,627 bp with a G+C content of 41.92% and 4,227 protein coding genes, 52 tRNAs, and 3 rRNAs.     

Prediction of neurotoxins based on their function and source

We have developed a method NTXpred for predicting neurotoxins and classifying them based on their function and origin. The dataset used in this study consists of 582 non-redundant, experimentally annotated neurotoxins obtained from Swiss-Prot. A number of modules have been developed for predicting neurotoxins using residue composition based on feed-forwarded neural network (FNN), recurrent neural network (RNN), support vector machine (SVM) and achieved maximum accuracy of 84.19%, 92.75%, 97.72% respectively. In addition, SVM modules have been developed for classifying neurotoxins based on their source (e.g., eubacteria, cnidarians, molluscs, arthropods have been and chordate) using amino acid composition and dipeptide composition and achieved maximum overall accuracy of 78.94% and 88.07% respectively. The overall accuracy increased to 92.10%, when the evolutionary information obtained from PSI-BLAST was combined with SVM module of source classification. We have also developed SVM modules for classifying neurotoxins based on functions using amino acid, dipeptide composition and achieved overall accuracy of 83.11%, 91.10% respectively. The overall accuracy of function classification improved to 95.11%, when PSI-BLAST output was combined with SVM module. All the modules developed in this study were evaluated using five-fold cross-validation technique. The NTXpred is available at www.imtech.res.in/raghava/ntxpred/ and mirror site at http://bioinformatics.uams.edu/mirror/ntxpred.