Showing papers by "Jawaharlal Nehru University published in 2005"

The genome of the protist parasite Entamoeba histolytica

Abstract: Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.

Multidrug resistance in yeast Candida.

Abstract: The opportunistic human pathogens Candida albicans and other non-albicans species have acquired considerable significance in the recent past due to the enhanced susceptibility of immunocompromised patients. These pathogenic species of Candida derive their importance not only from the severity of their infections but also from their ability to develop resistance against antifungals. Widespread and prolonged use of azoles has led to the rapid development of the phenomenon of multidrug resistance (MDR), which poses a major hurdle in antifungal therapy. Various mechanisms that contribute to the development of MDR have been implicated in Candida as well as in other human fungal pathogens, and some of these include overexpression of or mutations in the target enzyme of azoles, lanosterol 14 alpha-demethylase, and transcriptional activation of genes encoding drug efflux pump proteins belonging to ATP-binding cassette (ABC) as well as to major facilitator superfamilies (MFS) of transporters. The ABC transporters, CDR1, CDR2, and an MFS pump CaMDR1, play a key role in azole resistance as deduced from their high level of expression found in several azole-resistant clinical isolates.

The kin system as a poverty trap

Abstract: An institution found in many traditional societies is the extended family system (kin system), an informal system of shared rights and obligations among extended family for the purpose of mutual assistance. In predominantly non-market economies, the kin system is a valuable institution providing critical community goods and insurance services in the absence of market or public provision. But what happens when the market sector grows in the process of economic development? How do the members of kin groups respond, individually and collectively, to such changes? When the kin system meets the modern economy, does the kin system act as a vehicle of progress helping its members adapt, or as an instrument of stagnation holding back its members from benefiting from market development? In reality, the consequences of membership in a kin group have been varied for people in different parts of the world. Hoff and Sen characterize the conditions under which the kin system becomes a dysfunctional institution when facing an expanding modern economy. The authors first show that when there are moral hazard problems in the modern sector, the kin system may exacerbate them. When modern sector employers foresee that, they will offer employment opportunities on inferior terms to members of ethnic groups that practice the kin system. These entry barriers in the market, in turn, create an incentive for some individuals to break ties with their kin group, which hurts members of the group who stay back in the traditional sector. The authors then show in a simple migration model that if a kin group can take collective action to raise exit barriers, then even if migrating to the modern sector and breaking ties increases aggregate welfare (and even if a majority of members are expected to gain ex post, after the resolution of uncertainty about the identity of the winners and losers), a majority of agents within a kin group may support ex ante raising the exit barrier to prevent movement to the modern sector. This result is an example of the bias toward the status quo analyzed by Raquel Fernandez and Dani Rodrik in the context of trade reform. The authors do not claim that all kin groups will necessarily exhibit such a bias against beneficial regime changes. But they provide a clear intuition about the forces that can lead to the collective conservatism of a kin system facing expanding opportunities in a market economy-forces that can lead the kin group to become a poverty trap for its members.

Hydrogen peroxide modulates meiotic cell cycle and induces morphological features characteristic of apoptosis in rat oocytes cultured in vitro.

Abstract: Hydrogen peroxide (H2O2) is known to induce cell cycle arrest and apoptosis in various somatic cell types cultured in vitro. We hypothesize that this reactive oxygen species (ROS) could modulate cell cycle and induce morphological features characteristics of apoptosis in oocytes cultured in vitro. To test this hypothesis, immature and mature oocytes were cultured in medium containing various doses of H2O2 with or without caspase-3 inhibitor for various times. The treatment of H2O2 induced germinal vesicle break down (GVBD) in all immature oocytes followed by initiation of shrinkage. Some of immature oocytes (but not mature oocytes) also showed membrane blebbing. On the other hand, H2O2 treatment inhibited first polar body emission in mature oocytes just prior to initiation of shrinkage. The cytoplasmic granulation and fragmentation into apoptotic bodies were observed in mature oocytes during later stages of H2O2 treatment. The shrinkage was induced by H2O2 in a dose- and time-dependent manner in both immature and mature oocytes. Although, H2O2-induced degeneration was observed in both immature and mature oocytes after 2.0 hrs of treatment, immature oocytes were more susceptible to undergo quick shrinkage, membrane blebbing and degeneration. Co-addition of caspase-3 inhibitor prevented shrinkage and degeneration of both immature and mature oocytes except membrane blebbing that was observed at higher doses of H2O2 after 1.0 hr of culture. Treatment of H2O2 induced bax protein expression (3 times), DNA fragmentation and caspase-3 activity (2.5 times) in oocytes undergoing morphological apoptotic changes. These findings clearly suggest that H2O2 induced GVBD in immature oocytes, inhibited first polar body extrusion in mature oocytes prior to initiation of morphological changes characteristic of apoptosis such as shrinkage, membrane blebbing and cytoplasmic fragmentation prior to degeneration.

Combined treatment of sodium orthovanadate and Momordica charantia fruit extract prevents alterations in lipid profile and lipogenic enzymes in alloxan diabetic rats.

Abstract: Momordica charantia Linn., commonly called bitter gourd, is a medicinal plant used in the Ayurvedic system of medicine for treating various diseases including diabetes mellitus. Sodium orthovanadate (SOV) is also well-known insulin mimetic and an antidiabetic compound. Our laboratory has been using reduced doses of SOV along with administration of herbal extracts to alloxan diabetic rats and has established this combination as a good antihyperglycemic agent. The present study was undertaken to investigate the effects of treatment of Momordica fruit extract (MFE) and sodium orthovanadate, separately and in combination, on serum and tissue lipid profile and on the activities of lipogenic enzymes in alloxan induced diabetic rats. The results show that there was a significant (p < 0.01) increase in serum total lipids, triglycerides and total cholesterol levels after 21 days of alloxan diabetes. In the liver and kidney of diabetic rats the levels of total lipids and triglycerides also increased significantly (p < 0.01) while levels of total cholesterol decreased significantly (p < 0.01 and p < 0.05, respectively). The lipogenic enzymes showed decreased activity in the diabetic liver, while in kidney they showed an increased activity. When compared with the controls these changes were significant. The treatment of alloxan diabetic rats with MFE and SOV prevented these alterations and maintained all parameters near control values. Most effective prevention was however observed in a combined treatment of Momordica with a reduced dose of SOV (0.2%). The results suggest that Momordica fruit extract and SOV exhibit hypolipidemic as well as hypoglycemic effect in diabetic rats and their effect is pronounced when administered in combination. (Mol Cell Biochem 268: 111–120, 2005)

Direct current electrical characterization of ds-DNA in nanogap junctions

Abstract: Measurements of DNA conductivity, hybridization, and melting using electronic means can have wide applications in molecular electronics and biological sensors. We have fabricated nanogap break-junctions by electromigration through thin gold-on-titanium films. 18-mer thiolated ds-DNA molecules were covalently attached between the electrodes and dc electrical measurements were done. The conductance was measured through the molecule before and after a temperature ramp from 300 to 400 K. A dramatic decrease in conductance was observed, analogous to an electrical fuse, possibly attributed to complete or partial denaturing of the ds-DNA molecules bridging the nanogaps. We also show evidence that the dc resistance of dry DNA strands of the same length decreases with increasing guanine-cytosine content in the sequence with values ranging from 10 M Ω to 2 G Ω. These findings can have important consequences in DNA-based molecular electronics and direct label-free detection of DNA hybridization.

Weight based adaptive clustering in wireless ad hoc networks

Abstract: This paper proposes a new weight based adaptive clustering algorithm (WBACA) for mobile ad-hoc networks (MANETs). MANETs are multi-hop wireless packet networks in which all the nodes cooperatively maintain network connectivity without the aid of any infrastructure networks. The proposed WBACA takes into account the transmission power, transmission rate, mobility, battery power and the degree of a node for forming clusters. Unlike the lowest-ID algorithm, which finds only the local minima of IDs and the weighted clustering algorithm (WCA), which finds the global minima of weights, the proposed WBACA finds the local minima of weights for the clustering process. Through simulations, we have compared the performance of our algorithm with that of the lowest-ID and WCA algorithms in terms of the number of clusters formed, number of reaffiliations, and the time delay in starting up the clustering process. The results demonstrate the superior performance of the proposed algorithm.

Microbial Diversity in Soils

Abstract: Soil microbiology emerged as a distinct branch of soil science in 1838 after the French agricultural chemist and farmer, Boussingault, showed that legumes could obtain nitrogen from air when grown in soil which was not heated. Fifty years later, a Dutch scientist, Beijerinck, isolated bacteria from nodules of legume roots. Since then, a number of investigations have been conducted in the area of soil microbiology. However, scientists are still investigating soil microbial diversity. Soil is the outer covering of the earth, which consists of loosely arranged layers of materials composed of inorganic and organic compounds in different stages of organization (Tate 1995; Kapoor et al. 2002). It is a natural medium inwhichmicrobes live,multiply and die.Microbial diversity in the soil is a critical environmental topic that concerns people from all walks of life. Interest in microbial diversity has grown rapidly in the scientific community (Wilson 1988; Franklin 1993; Benizri et al. 2002). Increasing attention is being drawn to microorganisms because the fertility of soil depends not only on its chemical composition, but also on the qualitative and quantitative nature of microorganisms inhabiting it. Maintenance of viable, diverse populations and functioning microbial communities in the soil is essential for sustainable agriculture (Beare et al. 1995; Benizri et al. 2002). Soil contains a wide range of microorganisms descried as a ‘black box’ (Paul and Clark 1989). Microorganisms are generally divided into five major taxonomic categories: algae, bacteria, fungi, protists and viruses (Prescott et al. 1996;Hurst 2002). In soil, they are closely associated with soil particles, mainly clay– organic matter complexes (Foster 1988). Often, microbes can be found as single cells or as microcolonies embedded in a matrix of polysaccha-

Mountain Biodiversity, Land Use Dynamics and Traditional Ecological Knowledge

Abstract: Traditional mountain societies are characterized by their close interconnection with nature and natural resources. They depend upon natural resources and biodiversity for their sustainable livelihood concerns (Ramakrishnan 1992a; Ramakrishnan et al. 1994; 1996). This linkage with nature and natural resources extends beyond the economic realm; social, cultural and spiritual dimensions also play a significant role (Ramakrishnan et al. 1998). Traditional mountain societies have a holistic view of the ecosystem and the social system. This relationship with nature is based on coexistence rather than competition, which results in agricultural strategies that are adapted to the natural environment and the sustainable use of natural resources. The result of this relationship is a set of institutional arrangements that evolved towards ecological prudence. The ultimate objective is the sustainable use of natural resources through compromises between environmental risks on the one hand, and productivity concerns on the other.

Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans.

Abstract: The recent completion of the sequencing project of the opportunistic human pathogenic yeast, Candida albicans (http://www.ncbi.nlm.nih.gov/), led us to analyze and classify its ATP-binding cassette (ABC) proteins, which constitute one of the largest superfamilies of proteins. Some of its members are multidrug transporters responsible for the commonly encountered problem of antifungal resistance. TBLASTN searches together with domain analysis identified 81 nucleotide-binding domains, which belong to 51 different putative open reading frames. Considering that each allelic pair represents a single ABC protein of the Candida genome, the total number of putative members of this superfamily is 28. Domain organization, sequence-based analysis and self-organizing map-based clustering led to the classification of Candida ABC proteins into 6 distinct subfamilies. Each subfamily from C. albicans has an equivalent in Saccharomyces cerevisiae suggesting a close evolutionary relationship between the two yeasts. Our searches also led to the identification of a new motif to each subfamily in Candida that could be used to identify sequences from the corresponding subfamily in other organisms. It is hoped that the inventory of Candida ABC transporters thus created will provide new insights into the role of ABC proteins in antifungal resistance as well as help in the functional characterization of the superfamily of these proteins.

TLR2 Arg677Trp polymorphism in leprosy: revisited

Abstract: We investigated the Toll-like receptor 2 (TLR2) Arg677Trp polymorphism, associated with lepromatous leprosy in the Korean population and shown to abrogate TLR2-mediated signalling in response to mycobacterial ligands, in 286 Indian leprosy patients and 183 ethnically matched controls. The case-control comparison also involved investigation of possible variation(s) in the promoter region of the TLR2 gene. Genotyping results after direct PCR sequencing showed that the TLR2 Arg677Trp polymorphism associated with lepromatous leprosy in the Korean population is not a true polymorphism of the TLR2 gene and has resulted from the variation present in the 93% homologous duplicated region of TLR2 exon 3 present approximately 23 kb upstream.

Changes in agricultural biodiversity: Implications for sustainable livelihood in the Himalaya

Abstract: Himalayan mountain system is distinguished globally for a rich biodiversity and for its role in regulating the climate of the South Asia. Traditional crop-livestock mixed farming in the Himalaya is highly dependent on forests for fodder and manure prepared from forest leaf litter and livestock excreta. Apart from sustaining farm production, forests provide a variety of other tangible and intangible benefits, which are critical for sustainable livelihood of not only 115 million mountain people, but also many more people living in the adjoining plains. Extension of agricultural landuse coupled with replacement of traditional staple food crops by cash crops and of multipurpose agroforestry trees by fruit trees are widespread changes. Cultivation of Fagopyrum esculentum, Fagopyrum tataricum, Panicum miliaceum, Setaria italica and Pisum arvense has been almost abandoned. Increasing stress on cash crops is driven by a socio-cultural change from subsistence to market economy facilitated by improvement in accessibility and supply of staple food grains at subsidized price by the government. Farmers have gained substantial economic benefits from cash crops. However, loss of agrobiodiversity implies more risks to local livelihood in the events of downfall in market price/demand of cash crops, termination of supply of staple food grains at subsidized price, pest outbreaks in a cash crop dominated homogeneous landscape and abnormal climate years. Indigenous innovations enabling improvement in farm economy by conserving and/enhancing agrobiodiversity do exist, but are highly localized. The changes in agrobiodiversity are such that soil loss and run-off from the croplands have dramatically increased together with increase in local pressure on forests. As farm productivity is maintained with forest-based inputs, continued depletion of forest resources will result in poor economic returns from agriculture to local people, apart from loss of global benefits from Himalayan forests. Interventions including improvement in traditional manure and management of on-farm trees, participatory development of agroforestry in degraded forest lands and policies favoring economic benefits to local people from non-timber forest products could reduce the risks of decline in agricultural biodiversity and associated threats to livelihoods and Himalayan ecosystems.

Cooption and Resistance: Two Faces of Global Administrative Law

Abstract: This paper critiques the Global Administrative Law (GAL) initiative from a Third World perspective. The paper argues that, in the absence of a simultaneous critique and reform of substantive law, GAL has only limited potential to contribute to justice in the international system, and indeed may legitimize unjust laws and institutions. Existing international institutions are not, for the most part, being made more participatory and responsive to the concerns of developing countries and its peoples. Nevertheless, GAL may serve as a valuable instrument of change, much as administrative law has done through its use by social movements in some cases in India. This argument forms the basis for an analysis of the problems of increasing participation, transparency, and accountability in the Codex Alimentarius and in UNHCR refugee status determination. In situations of such unequal power, social movements and concerned NGOs must play key roles, and administrative mechanisms of information disclosure, participation, and review can facilitate this. Thus GAL can act as an instrument of resistance and change, but only in highly specific conditions, and only where GAL does not entail a complete separation between substantive and procedural/administrative rules.

Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans.

Abstract: In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1 ,o fCandida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells. The loss of mannosyl diinositol diphosphoceramide [M(IP)2C] in the ipt1 disruptant, however, resulted in increased sensitivity to drugs like 4-nitroquinoline oxide, terbinafine, o-phenanthroline, fluconazole, itraconazole, and ketoconazole. The increase in drug susceptibilities of ipt1 cells was linked to an altered sphingolipid composition, which appeared to be due to the impaired functionality of Cdr1p, a major drug efflux pump of C. albicans that belongs to the ATP binding cassette superfamily. Our confocal and Western blotting results demonstrated that surface localization of green fluorescent protein-tagged Cdr1p was affected in ipt1 disruptant cells. Poor surface localization of Cdr1p resulted in an impaired ability to efflux fluconazole and rhodamine 6G. The effect of mannosyl inositol phosphoceramide accumulation in the ipt1 mutant and the absence of M(IP)2C from the ipt1 mutant on the efflux of drug substrates was very selective. The efflux of methotrexate, a specific substrate of CaMdr1p, another major efflux pump of major facilitator superfamily, remained unaffected in ipt1 mutant cells. Interestingly, changes in sphingolipid composition affected the ability of mutant cells to form proper hyphae in various media. Taken together, our results demonstrate that an altered composition of sphingolipid, which is among the major constituents of membrane rafts, affects the drug susceptibilities and morphogenesis of C. albicans. The early steps in mammalian and fungal sphingolipid synthesis are conserved, but finally, they diverge to produce structurally and chemically different types of sphingoid bases, ceramides, and complex sphingolipids (12). Therefore, over the years, the sphingolipid biosynthetic pathway has been exploited as an antifungal drug target in pathogenic yeasts (24, 29). Unlike mammals, fungi do not have phosphatidylcholine as part of their polar head group in the sphingolipids; instead, they have phosphoinositol, which is transferred by Aur1p to the C-1 hydroxyl of ceramide to make inositol phosphoceramide (IPC) (6, 7). IPC is further modified by the addition of mannose by Csg1p, Csg2p, and Vrg4p to make mannosyl inositol phosphoceramide (MIPC) and the addition of a second inositol phosphate group by Ipt1p to make mannosyl diinositol diphosphoceramide [M(IP)2C] (6, 7). The biosynthesis of sphingolipids starts in the endoplasmic reticulum and proceeds up to the formation of ceramides (12). Subsequently, complex fungal sphingolipids [IPC, MIPC, and M(IP)2C] are synthesized in the Golgi apparatus. Recent reports have suggested that the biosynthesis of these sphingolipids is critical to the maintenance of plasma membrane (PM) function; however,

Bonded Labour in India: its Incidence and Pattern

Abstract: The review provides compelling evidence of the persistence of bonded labour in a wide range of economic sectors and in many different States. Although the more traditional forms of agrarian labour attachment in India have declined substantially, new forms of bondage have emerged in more modern agricultural as well as in the informal economy. Migrant labourers appear particularly vulnerable to bonded labour exploitation today, through recruitment systems where labour contractors and intermediaries lure ill-informed workers from their home communities with advance payments and false promises of well-paid, decent work. The paper also addresses some of the proactive measures taken by the Government of India, its civil society partners and the ILO to address the prevention and rehabilitation of bonded labour.

Chemopreventive potential of Triphala (a composite Indian drug) on benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system.

Abstract: The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% triphala containing diet. Tumor burden was 7.27 +/- 1.16 in the B(a)P treated control group, whereas it reduced to 3.00 +/- 0.82 (p < 0.005) by 2.5% dose and 2.33 +/- 1.03 (p < 0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17 +/- 0.75 (p < 0.001) and 2.00 +/- 0.71 (p < 0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential.

Domain growth in Ising systems with quenched disorder

Abstract: We present results from extensive Monte Carlo (MC) simulations of domain growth in ferromagnets and binary mixtures with quenched disorder. These are modeled by the random-bond Ising model and the dilute Ising model with either nonconserved (Glauber) spin-flip kinetics or conserved (Kawasaki) spin-exchange kinetics. In all cases, our MC results are consistent with power-law growth with an exponent theta(T, epsilon) which depends on the quench temperature T and the disorder amplitude epsilon. Such exponents arise naturally when the coarsening domains are trapped by energy barriers that grow logarithmically with the domain size. Our MC results show excellent agreement with the predicted dependence of theta(T, epsilon).