An Interpretable Predictive Model of Vaccine Utilization for Tanzania.

Providing accurate utilization forecasts is key to maintaining optimal vaccine stocks in any health facility. Current approaches to vaccine utilization forecasting are based on often outdated population census data, and rely on weak, low-dimensional demand forecasting models. Further, these models provide very little insights into factors that influence vaccine utilization.

Invariance and plasticity in the Drosophila melanogaster metabolomic network in response to temperature.

Background: Metabolomic responses to extreme thermal stress have recently been investigated in Drosophila melanogaster. However, a network level understanding of metabolomic responses to longer and less drastic temperature changes, which more closely reflect variation in natural ambient temperatures experienced during development and adulthood, is currently lacking. Here we use high-resolution, non-targeted metabolomics to dissect metabolomic changes in D.

Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner.

Background: Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer.

Anterior tongue cancer with no history of tobacco and alcohol use may be a distinct molecular and clinical entity.

Background: A small, albeit significant, number of head and neck squamous cell carcinoma (HNSCC) patients has no history of tobacco and alcohol use. Such non-habits associated HNSCCs may represent a distinct clinical entity and exhibit increased aggressiveness. The objective of the study was to understand differences in molecular etiology of habits, and non-habits associated tongue carcinomas.

The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage.

Background: We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species' physiological capacities to withstand extreme anoxia and tissue freezing.

Results: Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle.

Comparative analysis of DNA word abundances in four yeast genomes using a novel statistical background model.

Previous studies have shown that the identification and analysis of both abundant and rare k-mers or "DNA words of length k" in genomic sequences using suitable statistical background models can reveal biologically significant sequence elements. Other studies have investigated the uni/multimodal distribution of k-mer abundances or "k-mer spectra" in different DNA sequences. However, the existing background models are affected to varying extents by compositional bias.

Whole-genome sequences of two clinical isolates of Mycobacterium tuberculosis from Kerala, South India.

We report the annotated genome sequence of two clinical isolates of Mycobacterium tuberculosis isolated from Kerala, India.

A miR-centric view of head and neck cancers.

Head and Neck Squamous Cell Carcinomas (HNSCCs) constitute the sixth most common cancer worldwide with an average 5-year survival rate of around 50%. Several microRNAs, small non-coding RNAs involved in post-transcriptional gene regulation, have been linked to HNSCC based on their differential expression in tumors. Here, we present a compilation of multiple types of information on each HNSCC linked miRNA including their expression status in tumors, their molecular targets relevant to cancer, results of gene manipulation studies and association with clinical outcome.

Genetic characterization of 2006-2008 isolates of Chikungunya virus from Kerala, South India, by whole genome sequence analysis.

Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic febrile infections characterized by severe and prolonged arthralgia. In the present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120; 2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala, South India, were analyzed for genetic variations by sequencing the 11798 bp whole genome of the virus. A total of 37 novel mutations were identified and they were predominant in the 2007 and 2008 isolates among the six isolates studied.

Mutational analysis of Smad7 in human cervical cancer.

Our aim was to carry out mutational analysis of Smad7 exon 4 that codes for the Smad7 MH2 domain in human cervical cancer tissues. This study is warranted since genetic abnormalities of components of the transforming growth factor-beta (TGF-beta)/Smad signaling system have been implicated in a variety of human cancers. Further, Smad7 is an important member of the Smad family that functions as a negative feedback regulator of TGF-beta responses.

Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1.

Fluoxetine, a well-known antidepressant used clinically for mental depression has gained attention in cancer research owing to its chemosensitizing potential in drug resistant cell lines. Some preliminary reports, however, suggested its independent cytotoxic potential which is not yet well characterized. Our aim in this study was to characterize its antiproliferative activity in tumor cells and to further elucidate the mechanism.

Structure-function relationship of inhibitory Smads: Structural flexibility contributes to functional divergence.

Smads are a small family of eukaryotic transcription regulators that play key roles in the transforming growth factor-beta signaling cascade. Smad6 and Smad7, the inhibitory or I-Smads, inhibit signaling downstream of TGF-beta type I receptors, thereby acting as negative regulators of signaling mediated by TGF-beta superfamily of ligands. Smad6 is known to specifically inhibit BMP type I receptor mediated signaling, while Smad7 is a more general inhibitor, able to block signaling mediated by a set of related TGF-beta type I receptors, including type I receptors for BMP and TGF-beta/Activin.

Detailed comparison of the protein-ligand docking efficiencies of GOLD, a commercial package and ArgusLab, a licensable freeware.

Molecular docking and virtual screening based on molecular docking have become an integral part of many modern structure-based drug discovery efforts. Hence, it becomes a useful endeavor to evaluate existing docking programs, which can assist in the choice of the most suitable docking algorithm for any particular study. The objective of the current study was to evaluate the ability of ArgusLab 4.

Single nucleotide polymorphisms of DNA repair genes XRCC1 and XPD and its molecular mapping in Indian oral cancer.

Tobacco users with diminished ability to repair somatic mutations may be more susceptible to tobacco attributable cancers. The distribution of single nucleotide polymorphisms (SNPs) in DNA repair genes XRCC1 and XPD in 110 oral carcinoma cases, 84 leukoplakia and 110 controls belonging to the Travancore South Indian population were examined. SNPs investigated included Arg194Trp, Arg280His, and Arg399Gln of the XRCC1 gene and Lys751Gln of the XPD gene.

Homology modeling of the DNA-binding domain of human Smad5: a molecular model for inhibitor design.

Members of the Smad protein family function as signal transducers of the transforming growth factor (TGF-beta) superfamily proteins. The human Smad5 protein, a signal transducer downstream of TGF-beta/BMP receptors, is composed of N-terminal DNA binding domain (MH1) and C-terminal protein-protein interaction domain (MH2) connected together by a linker motif. We used homology-modeling techniques to generate a reliable molecular model of the Smad5 MH1 domain based on the crystal structure of Smad3 MH1 domain.