Biomedical subjects

Anil K Ghosh

Publications and source records attributed to Anil K Ghosh.

8 recordsLinked to original sources

PubMed2006

Protective role of S-adenosyl-L-methionine against hydrochloric acid stress in Saccharomyces cerevisiae.

S-adenosyl-L-methionine (AdoMet, 1mM) protects the stationary phase cells of Saccharomyces cerevisiae against the killing effect of acid (10mM HCl, pH approximately 2). Both the acid and the acid plus AdoMet treatment for 2h increased the plasma membrane H(+)-ATPase activity; thereafter it decreased to the basal level. AdoMet partially recovered the intracellular pH (pH(in)) that dropped in presence of acid. AdoMet treatment facilitated acid induced phospholipid biosynthesis as well as membrane proliferation, which was reflected in the cellular lipid composition.

Cytoprotection↗

PubMed2006

Multiscale classification using nearest neighbor density estimates.

Density estimates based on k-nearest neighbors have useful applications in nonparametric discriminant analysis. In classification problems, optimal values of k are usually estimated by minimizing the cross-validated misclassification rates. However, these cross-validation techniques allow only one value of k for each population density estimate, while in a classification problem, the optimum value of k for a class may also depend on its competing population densities. Further, it is computationally difficult to minimize the cross-validated error rate when there are several competing populations. Moreover, in addition to depending on the entire training data set, a good choice of k should also depend on the specific observation to be classified. Therefore, instead of using a single value of k for each population density estimate, it is more useful in practice to consider the results for multiple values of k to arrive at the final decision. This paper presents one such approach along with a graphical device, which gives more information about classification results for various choices of k and the related statistical uncertainties present there. The utility of this proposed methodology has been illustrated using some benchmark data sets.

Algorithms↗

PubMed2005

Extracellular trehalose utilization by Saccharomyces cerevisiae.

Two haploid strains of Saccharomyces cerevisiae viz. MATalpha and MATa were grown in glucose and trehalose medium and growth patterns were compared. Both strains show similar growth, except for an extended lag phase in trehalose grown cells. In both trehalose grown strains increase in activities of both extracellular trehalase activities and simultaneous decrease in extracellular trehalose level was seen. This coincided with a sharp increase in extracellular glucose level and beginning of log phase of growth. Alcohol production was also observed. Secreted trehalase activity was detected, in addition to periplasmic activity. It appeared that extracellular trehalose was hydrolyzed into glucose by extracellular trehalase activity. This glucose was utilized by the cells for growth. The alcohol formation was due to the fermentation of glucose. Addition of extracellular trehalase caused reduction in the lag phase when grown in trehalose medium, supporting our hypothesis of extracellular utilization of trehalose.

Culture Media↗

PubMed2005

Transcriptome analysis of Anopheles stephensi-Plasmodium berghei interactions.

Simultaneous microarray-based transcription analysis of 4987 Anopheles stephensi midgut and Plasmodium berghei infection stage specific cDNAs was done at seven successive time points: 6, 20 and 40h, and 4, 8, 14 and 20 days after ingestion of malaria infected blood. The study reveals the molecular components of several Anopheles processes relating to blood digestion, midgut expansion and response to Plasmodium-infected blood such as digestive enzymes, transporters, cytoskeletal and structural components and stress and immune responsive factors. In parallel, the analysis provide detailed expression patterns of Plasmodium genes encoding essential developmental and metabolic factors and proteins implicated in interaction with the mosquito vector and vertebrate host such as kinases, transcription and translational factors, cytoskeletal components and a variety of surface proteins, some of which are potent vaccine targets. Temporal correlation between transcription profiles of both organisms identifies putative gene clusters of interacting processes, such as Plasmodium invasion of the midgut epithelium, Anopheles immune responses to Plasmodium infection, and apoptosis and expulsion of invaded midgut cells from the epithelium. Intriguing transcription patterns for highly variable Plasmodium surface antigens may indicate parasite strategies to avoid recognition by the mosquito's immune surveillance system.

Animals↗

PubMed2005

On visualization and aggregation of nearest neighbor classifiers.

Nearest neighbor classification is one of the simplest and most popular methods for statistical pattern recognition. A major issue in k-nearest neighbor classification is how to find an optimal value of the neighborhood parameter k. In practice, this value is generally estimated by the method of cross-validation. However, the ideal value of k in a classification problem not only depends on the entire data set, but also on the specific observation to be classified. Instead of using any single value of k, this paper studies results for a finite sequence of classifiers indexed by k. Along with the usual posterior probability estimates, a new measure, called the Bayesian measure of strength, is proposed and investigated in this paper as a measure of evidence for different classes. The results of these classifiers and their corresponding estimated misclassification probabilities are visually displayed using shaded strips. These plots provide an effective visualization of the evidence in favor of different classes when a given data point is to be classified. We also propose a simple weighted averaging technique that aggregates the results of different nearest neighbor classifiers to arrive at the final decision. Based on the analysis of several benchmark data sets, the proposed method is found to be better than using a single value of k.

Algorithms↗

PubMed2003

Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion.

Plasmodium, the causative agent of malaria, has to undergo sexual differentiation and development in anopheline mosquitoes for transmission to occur. To isolate genes specifically induced in both organisms during the early stages of Plasmodium differentiation in the mosquito, two cDNA libraries were constructed, one enriched for sequences expressed in differentiating Plasmodium berghei ookinetes and another enriched for sequences expressed in Anopheles stephensi guts containing invading ookinetes and early oocysts. Sequencing of 457 ookinete library clones and 652 early oocyst clones represented 175 and 346 unique expressed sequence tags, respectively. Nine of 13 Plasmodium and four of the five Anopheles novel expressed sequence tags analyzed on Northern blots were induced during ookinete differentiation and mosquito gut invasion. Ancaspase-7, an Anopheles effector caspase, is proteolytically activated during Plasmodium invasion of the midgut. WARP, a gene encoding a Plasmodium surface protein with a von Willebrand factor A-like adhesive domain, is expressed only in ookinetes and early oocysts. An anti-WARP polyclonal antibody strongly inhibits (70-92%) Plasmodium development in the mosquito, making it a candidate antigen for transmission blocking vaccines. The present results and those of an accompanying report (Srinivasan, P., Abraham, E. G., Ghosh, A. K., Valenzuela, J., Ribeiro, J. M. C., Dimopoulos G., Kafatos, F. C., Adams, J. H., and Jacobs-Lorena, M. (2004) J. Biol. Chem. 279, 5581-5587) provide the foundation for further analysis of Plasmodium differentiation in the mosquito and of mosquito responses to the parasite.

Amino Acid Sequence↗

PubMed2003

Analysis of the Plasmodium and Anopheles transcriptomes during oocyst differentiation.

Understanding the life cycle of the malaria parasite in its mosquito vector is essential for developing new strategies to combat this disease. Subtractive hybridization cDNA libraries were constructed that are enriched for Plasmodium berghei and Anopheles stephensi genes expressed during oocyst differentiation on the midgut. Sequencing of 1485 random clones led to the identification of 1137 unique expressed sequence tags. Of the 608 expressed sequence tags with data base hits, 320 (53%) had significant matches to the non-redundant protein data base, whereas 288 (47%) with matches only to genomic data bases represent novel Plasmodium and Anopheles genes. Transcription of six novel parasite genes and two previously identified asexual stage genes was up-regulated during oocyst differentiation. In addition, the mRNA for an Anopheles fibrinogen domain gene was induced on day 2 after an infectious blood meal, at the time of ookinete to oocyst differentiation. The subcellular distribution of MAEBL, a sporozoite surface protein, is developmentally regulated from presumed storage organelles in day 15 oocysts to uniform distribution on the surface in day 22 oocysts. This redistribution may reflect a sporozoite maturation program in preparation for salivary gland invasion. Furthermore, apical membrane antigen 1, another parasite surface molecule, is translationally regulated late in sporozoite development, suggesting a role during infection of the vertebrate host. The present results and those of an accompanying report (Abraham, E. G., Islam, S., Srinivasan, P., Ghosh, A. K., Valenzuela, J., Ribeiro, J. M., Kafatos, F. C., Dimopoulos, G., & Jacobs-Lorena, M. (2003) J. Biol. Chem. 279, 5573-5580) provide the foundation for studies seeking to understand at the molecular level Plasmodium development and its interactions with the mosquito.

Amino Acid Sequence↗

PubMed2002

Genetic transformation of mosquitoes: a quest for malaria control.

Malaria inflicts an enormous toll in human lives and this burden is increasing. Present means to fight the disease, such as drugs and insecticides, are insufficient. Moreover, an effective vaccine has not yet been developed. This review examines an alternative strategy for malaria control, namely the genetic modification of mosquitoes to make them inefficient vectors for the parasite. The article summarises progress made toward the development of transposable element vectors for germ line transformation and the search for mosquito markers of transformation. Also reviewed is the search for anti-malarial effector genes whose products can inhibit development of the parasite in the mosquito with minimal fitness burden. While much progress has been made, much work remains to be done. Future research directions are discussed.

Animals↗