Cytodiagnosis of filarial infections from an endemic area

OBJECTIVE: To throw light on cytologic findings as a possible mode of diagnosis of lymphatic filariasis. STUDY DESIGN: Filariasis has worldwide distribution, but lymphatic filariasis predominantly affects tropical and subtropical regions. Demonstration of microfilaremia, the specific test for diagnosis of lymphatic filariasis, often shows false negative results in endemic areas. The present study, done in an endemic area, showed the presence of microfilariae or adult worms of Wuchereria bancrofti in fine needle aspirates collected from amicrofilariaemic cases. In a few cases the discovery was incidental. A total 4,534 cases undergoing cytologic evaluation were carefully screened for the presence of adult worms or larvae, irrespective of clinical diagnosis. Microfilariae were demonstrated in both clinically suspected cases of filariasis and asymptomatic cases. RESULTS: A total of 1 positive cases were found; in 4 cases the clinical diagnosis was lymphatic filariasis, and 7 cases were asymptomatic. All 11 cases were amicrofilariaemic. CONCLUSION: Various sophisticated investigations are used for diagnosis of lymphatic filariasis without microfilaremia. Fine needle aspiration cytology, being a cheap, simple and easy procedure, may have some role in this field, but further detailed studies are needed before any final claim.     

Direct regulation of topoisomerase activity by a nucleoid-associated protein

The topological homeostasis of bacterial chromosomes is maintained by the balance between compaction and the topological organization of genomes. Two classes of proteins play major roles in chromosome organization: the nucleoid-associated proteins (NAPs) and topoisomerases. The NAPs bind DNA to compact the chromosome, whereas topoisomerases catalytically remove or introduce supercoils into the genome. We demonstrate that HU, a major NAP of Mycobacterium tuberculosis specifically stimulates the DNA relaxation ability of mycobacterial topoisomerase I (TopoI) at lower concentrations but interferes at higher concentrations. A direct physical interaction between M. tuberculosis HU (MtHU) and TopoI is necessary for enhancing enzyme activity both in vitro and in vivo. The interaction is between the amino terminal domain of MtHU and the carboxyl terminal domain of TopoI. Binding of MtHU did not affect the two catalytic trans-esterification steps but enhanced the DNA strand passage, requisite for the completion of DNA relaxation, a new mechanism for the regulation of topoisomerase activity. An interaction-deficient mutant of MtHU was compromised in enhancing the strand passage activity. The species-specific physical and functional cooperation between MtHU and TopoI may be the key to achieve the DNA relaxation levels needed to maintain the optimal superhelical density of mycobacterial genomes.     

Antitumor and proapoptotic effect of Abrus agglutinin derived peptide in Dalton's lymphoma tumor model

Abrus agglutinin peptide fractions obtained from 10 kD molecular weight cut off membrane permeate (10 kMP), was shown to have selective antiproliferative activity on several tumor cell lines with induction of apoptosis through mitochondrial pathway. The present study was designed to evaluate acute general toxicity and in vivo therapeutic effectiveness of 10 kMPP in Dalton's lymphoma (DL) mice model. The acute toxicity like body weight, peripheral blood cell count, lympho-hematological and biochemical parameters remained unaffected with 1mg/kg body weight and lower of 10 kMPP. The in vivo antitumor study indicated that there were 27%, 58.5% and 84.5% reduction in DL cell survival in 100, 200 and 500 microg/kg body weight of 10 kMPP, respectively. Analysis of the growth inhibitory mechanism in DL cells revealed nuclear fragmentation and condensation with appearance of the sub G0/G1 peak is indicative of apoptosis. Further, the Western blotting showed apoptosis was mediated by reduction in ratio of Bcl-2 and Bax protein expression, and activation of caspase-3 through release of cytochrome-c in DL cells. Kaplan-Meier survival analysis showed an effective antitumor response (53 ILS%) with dose of 500 microg/kg body weight. Our result showed that the novel peptides present in Abrus agglutinin possess potent antitumor properties which need to be further explored.     

Bayesian hierarchical spatially correlated functional data analysis with application to colon carcinogenesis

Summary .   In this article, we present new methods to analyze data from an experiment using rodent models to investigate the role of p27, an important cell-cycle mediator, in early colon carcinogenesis. The responses modeled here are essentially functions nested within a two-stage hierarchy. Standard functional data analysis literature focuses on a single stage of hierarchy and conditionally independent functions with near white noise. However, in our experiment, there is substantial biological motivation for the existence of spatial correlation among the functions, which arise from the locations of biological structures called colonic crypts: this possible functional correlation is a phenomenon we term crypt signaling . Thus, as a point of general methodology, we require an analysis that allows for functions to be correlated at the deepest level of the hierarchy. Our approach is fully Bayesian and uses Markov chain Monte Carlo methods for inference and estimation. Analysis of this data set gives new insights into the structure of p27 expression in early colon carcinogenesis and suggests the existence of significant crypt signaling. Our methodology uses regression splines, and because of the hierarchical nature of the data, dimension reduction of the covariance matrix of the spline coefficients is important: we suggest simple methods for overcoming this problem.     

Genetic diversity in two leading Plasmodium vivax malaria vaccine candidates AMA1 and MSP119 at three sites in India

Plasmodium vivax, a major contributor to the malaria burden in India, has the broadest geographic distribution and shows higher genetic diversity than P. falciparum. Here, we investigated the genetic diversity of two leading P. vivax vaccine candidate antigens, at three geographically diverse malaria-endemic regions in India. Pvama1 and Pvmsp1₁₉ partial coding sequences were generated from one hundred P. vivax isolates in India (Chennai n = 28, Nadiad n = 50 and Rourkela n = 22) and ~1100 published sequences from Asia, South America, North America, and Oceania regions included. These data were used to assess the genetic diversity and potential for vaccine candidacy of both antigens on a global scale. A total of 44 single nucleotide polymorphism (SNPs) were identified among 100 Indian Pvama1 sequences, including 10 synonymous and 34 nonsynonymous mutations. Nucleotide diversity was higher in Rourkela and Nadiad as compared to Chennai. Nucleotide diversity measures showed a strong balancing selection in Indian and global population for domain I of Pvama1, which suggests that it is a dominant target of the protective immune response. In contrast, the Pvmsp1₁₉ region showed highly conserved sequences in India and across the Oceania, South America, North America and Asia, demonstrating low genetic diversity in the global population when compared to Pvama1. Results suggest the possibility of including Pvmsp1₁₉ in a multivalent vaccine formulation against P. vivax infections. However, the high genetic diversity seen in Pvama1 would be more challenging for vaccine development.     

Marker-assisted pyramiding of <Emphasis Type="BoldItalic">Thinopyrum-</Emphasis>derived leaf rust resistance genes <Emphasis Type="BoldItalic">Lr19</Emphasis> and <Emphasis Type="BoldItalic">Lr24</Emphasis> in bread wheat variety HD2733

This study was undertaken to pyramid two effective leaf rust resistance genes (Lr19 and Lr24) derived from Thinopyrum (syn. Agropyron), in the susceptible, but agronomically superior wheat cultivar HD2733 using marker-assisted selection. In the year 2001, HD2733 was released for irrigated timely sown conditions of the north eastern plains zone (NEPZ) of India became susceptible to leaf rust, a major disease of the region. Background selection helped in developing near-isogenic lines (NILs) of HD2733 with Lr19 and Lr24 with 97.27 and \(98.94\%\), respectively, of genomic similarity with the parent cultivar, after two backcrossing and one generation of selfing. NILs were intercrossed to combine the genes Lr19 and Lr24. The combination of these two genes in the cultivar HD2733 is expected to provide durable leaf rust resistance in farmers’ fields.     

Biotechnological potential of immobilized algae for wastewater N, P and metal removal: A review

This presentation comprises a review on the use of immobilized algae for wastewater nitrogen, phosphorus and metal removal purposes. Details of the use of immobilized algae, the techniques of immobilization and the effects of immobilization on cell function are included. Particularly relevant in their use for heavy metal removal from wastewaters; upon enriching the biomass in metal, can be recoverd, thereby providing economic advantages. The use of immobilized microalgae in these processes is very adequate and offers significant advantages in bioreactors. The future of this area of algal cell biotechnology is considered.     

Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry

A crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry (MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information.