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Dutta, T.

Publications and source records attributed to Dutta, T..

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Rational Design of Peptide Vaccines for the Highly Lethal Nipah and Hendra Viruses

The Nipah virus disease is a lethal infection that has led to 40% to 75% fatalities in Malaysia, Bangladesh and India. The reports of human-to-human transmission documented in Bangladesh has raised the specter of pandemic potential and has caused the World Health Organization to list the Nipah virus as one of the pathogens to be considered for development of drugs and vaccines on urgent basis, neither of which exist against the Nipah virus as of now, although many proposals have been made and trials initiated. Given that there are established country-specific differences in the virus effects and fatalities, meeting the sudden need for a vaccine in case of an epidemic will require design, development and preparation for a peptide vaccine. Thus, we propose a protocol for creating peptide vaccines that can be tailor-made for these specific countries, an approach which is being advocated for the first time. Here, we analyze the surface proteins, Fusion protein and Glycoprotein, of the strains currently affecting the three countries on a large scale and determine the specific country-based epitope differences.

bioinformatics

Distinct Microbes, Metabolites, and Ecologies Define the Microbiome in Deficient and Proficient Mismatch Repair Colorectal Cancers

Background\n\nThe link between colorectal cancer (CRC) and the gut microbiome has been established, but the specific microbial species and their role in carcinogenesis remain controversial. Our understanding would be enhanced by better accounting for tumor subtype, microbial community interactions, metabolism, and ecology.\n\nMethods\n\nWe collected paired colon tumor and normal-adjacent tissue and mucosa samples from 83 individuals who underwent partial or total colectomies for CRC. Mismatch repair (MMR) status was determined in each tumor sample and classified as either deficient MMR (dMMR) or proficient MMR (pMMR) tumor subtypes. Samples underwent 16S rRNA gene sequencing and a subset of samples from 50 individuals were submitted for targeted metabolomic analysis to quantify amino acids and short-chain fatty acids. A PERMANOVA was used to identify the biological variables that explained variance within the microbial communities. dMMR and pMMR microbial communities were then analyzed separately using a generalized linear mixed effects model that accounted for MMR status, sample location, intra-subject sample correlation, and read depth. Genome-scale metabolic models were then used to generate microbial interaction networks for dMMR and pMMR microbial communities. We assessed global network properties as well as the metabolic influence of each microbe within the dMMR and pMMR networks.\n\nResults\n\nWe demonstrate distinct roles for microbes in dMMR and pMMR CRC. Sulfidogenic Fusobacterium nucleatum and hydrogen sulfide production were significantly enriched in dMMR CRC, but not pMMR CRC. We also surveyed the butyrate-producing microbial species, but did not find a significant difference in predicted or actual butyrate production between dMMR and pMMR microbial communities. Finally, we observed that dMMR microbial communities were predicted to be less stable than pMMR microbial communities. Community stability may play an important role in CRC development, progression, or immune activation within the respective MMR subtypes.\n\nConclusions\n\nIntegrating tumor biology and microbial ecology highlighted distinct microbial, metabolic, and ecological properties unique to dMMR and pMMR CRC. This approach could critically improve our ability to define, predict, prevent, and treat colorectal cancers.

cancer biology

Rhodosporidium toruloides: A new platform organism for conversion of lignocellulose into terpene biofuels and bioproducts

BackgroundEconomical conversion of lignocellulosic biomass into biofuels and bioproducts is central to the establishment of a robust bioeconomy. This requires a conversion host that is able to both efficiently assimilate the major lignocellulose-derived carbon sources and divert their metabolites toward specific bioproducts.\n\nResultsIn this study, the carotenogenic yeast Rhodosporidium toruloides was examined for its ability to convert lignocellulose into two non-native sesquiterpenes with biofuel (bisabolene) and pharmaceutical (amorphadiene) applications. We found that R. toruloides can efficiently convert a mixture of glucose and xylose from hydrolyzed lignocellulose into these bioproducts, and unlike many conventional production hosts, its growth and productivity were enhanced in lignocellulosic hydrolysates relative to purified substrates. This organism was demonstrated to have superior growth in corn stover hydrolysates prepared by two different pretreatment methods, one using a novel biocompatible ionic liquid (IL) choline -ketoglutarate, which produced 261 mg/L of bisabolene at bench-scale, and the other using an alkaline pretreatment, which produced 680 mg/L of bisabolene in a high gravity fed-batch bioreactor. Interestingly, R. toruloides was also observed to assimilate p-coumaric acid liberated from acylated grass lignin in the IL hydrolysate, a finding we verified with purified substrates. R. toruloides was also able to consume several additional compounds with aromatic motifs similar to lignin monomers, suggesting that this organism may have the metabolic potential to convert depolymerized lignin streams alongside lignocellulosic sugars.\n\nConclusionsThis study highlights the natural compatibility of R. toruloides with bioprocess conditions relevant to lignocellulosic biorefineries and demonstrates its ability to produce non-native terpenes.

bioengineering