Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection

The contest between the host factor APOBEC3G (A3G) and the HIV-1 protein Vif presents an attractive target of intervention. The extent to which the A3G-Vif interaction must be suppressed to tilt the balance in favor of A3G remains unknown. We employed stochastic simulations and mathematical modeling of the within-host dynamics and evolution of HIV-1 to estimate the fraction of progeny virions that must incorporate A3G to render productive infection unsustainable. Using three different approaches, we found consistently that a transition from sustained infection to suppression of productive infection occurred when the latter fraction exceeded similar to 0.8. The transition was triggered by A3G-induced hypermutations that led to premature stop codons compromising viral production and was consistent with driving the basic reproductive number, R-o, below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G-Vif axis. (C) 2013 Elsevier Inc. All rights reserved.

Varied Immune Response to FVIII: Presence of Proteolytic Antibodies Directed to Factor VIII in Different Human Pathologies

The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation of the complement and its activation, and activation of effector cells. In addition to this plethora of functions, antibodies are capable of expressing enzymatic activity. Antibodies with catalytic function are a result of the productive interplay between the highly evolved machinery of the immune system and the chemical framework used to induce them (antigens). Catalytic antibodies are immunoglobulins with an ability to catalyze the reactions involving the antigen for which they are specific. Catalytic immunoglobulins of the IgM and IgG isotypes have been detected in the serum of healthy donors. In addition, catalytic immunoglobulins of the IgA isotype have been detected in the milk of healthy mothers. Conversely, antigen-specific hydrolytic antibodies have been reported in a number of inflammatory, autoimmune, and neoplastic disorders. The pathophysiological occurrence and relevance of catalytic antibodies remains a debated issue. Through the description of the hydrolysis of coagulation factor VIII as model target antigen, we propose that catalytic antibodies directed to the coagulation factor VIII may play a beneficial or a deleterious role depending on the immuno-inflammatory condition under which they occur.

An approach for studying the mediators of pathogenesis in Mycobacterium tuberculosis

Mycobacterium tuberculosis is an example of an intracellular pathogen that mediates the disease state through complex interactions with the host's immune system. Not only does this organism replicate in the hostile environment prevailing within the infected macrophage, but it has also developed intricate mechanisms to inhibit several defence mechanisms of the host's immune system. It is postulated here that the mediators of these interactions with the host are products of differentially expressed genes in the pathogen, B and T fell responses of the host are hence to be used as tools to identify such gene products from an expression library of the Mycobacterium tuberculosis genome. The various pathways of generating a productive immune response that may be targeted by the pathogen are discussed.

Mutations in beta ` subunit of Escherichia coli RNA polymerase perturb the activator polymerase functional interaction required for promoter clearance

P>Transcription activator C employs a unique mechanism to activate mom gene of bacteriophage Mu. The activation process involves, facilitating the recruitment of RNA polymerase (RNAP) by altering the topology of the promoter and enhancing the promoter clearance by reducing the abortive transcription. To understand the basis of this multi-step activation mechanism, we investigated the nature of the physical interaction between C and RNAP during the process. A variety of assays revealed that only DNA-bound C contacts the beta' subunit of RNAP. Consistent to these results, we have also isolated RNAP mutants having mutations in the beta' subunit which were compromised in C-mediated activation. Mutant RNAPs show reduced productive transcription and increased abortive initiation specifically at the C-dependent mom promoter. Positive control (pc) mutants of C, defective in interaction with RNAP, retained the property of recruiting RNAP to the promoter but were unable to enhance promoter clearance. These results strongly suggest that the recruitment of RNAP to the mom promoter does not require physical interaction with C, whereas a contact between the beta' subunit and the activator, and the subsequent allosteric changes in the active site of the enzyme are essential for the enhancement of promoter clearance.

Identifying Robust Plans through Plan Diagram Reduction

Estimates of predicate selectivities by database query optimizers often differ significantly from those actually encountered during query execution, leading to poor plan choices and inflated response times. In this paper, we investigate mitigating this problem by replacing selectivity error-sensitive plan choices with alternative plans that provide robust performance. Our approach is based on the recent observation that even the complex and dense "plan diagrams" associated with industrial-strength optimizers can be efficiently reduced to "anorexic" equivalents featuring only a few plans, without materially impacting query processing quality. Extensive experimentation with a rich set of TPC-H and TPC-DS-based query templates in a variety of database environments indicate that plan diagram reduction typically retains plans that are substantially resistant to selectivity errors on the base relations. However, it can sometimes also be severely counter-productive, with the replacements performing much worse. We address this problem through a generalized mathematical characterization of plan cost behavior over the parameter space, which lends itself to efficient criteria of when it is safe to reduce. Our strategies are fully non-invasive and have been implemented in the Picasso optimizer visualization tool.

Wetlands of Greater Bangalore, India: Automatic Delineation through Pattern Classifiers

Wetlands are the most productive and biologically diverse but very fragile ecosystems. They are vulnerable to even small changes in their biotic and abiotic factors. In recent years, there has been concern over the continuous degradation of wetlands due to unplanned developmental activities. This necessitates inventorying, mapping, and monitoring of wetlands to implement sustainable management approaches. The principal objective of this work is to evolve a strategy to identify and monitor wetlands using temporal remote sensing (RS) data. Pattern classifiers were used to extract wetlands automatically from NIR bands of MODIS, Landsat MSS and Landsat TM remote sensing data. MODIS provided data for 2002 to 2007, while for 1973 and 1992 IR Bands of Landsat MSS and TM (79m and 30m spatial resolution) data were used. Principal components of IR bands of MODIS (250 m) were fused with IRS LISS-3 NIR (23.5 m). To extract wetlands, statistical unsupervised learning of IR bands for the respective temporal data was performed using Bayesian approach based on prior probability, mean and covariance. Temporal analysis of wetlands indicates a sharp decline of 58% in Greater Bangalore attributing to intense urbanization processes, evident from a 466% increase in built-up area from 1973 to 2007.

Ecological and Socio Economic Assesment of Varthur Wetlnd, Bengaluru (India)

Wetlands are the most productive ecosystems, recognized globally for its vital role in sustaining a wide array of biodiversity and provide goods and services. However despite their important role in maintaining the ecology and economy, wetlands in India are endangered by inattention and lack of appreciation for their role. Increased anthropogenic activities such as intense agriculture practices, indiscriminate disposal of industrial effluents and sewage wastes have altered the physical, chemical as well as biological integrity of the ecosystem. This has resulted in the ecological degradation, which is evident from the current ecosystem valuation of Varthur wetland. Global valuation of coastal wetland ecosystem shows a total of 14,785/ha US$ annual economic value. An earlier study of relatively pristine wetland in Bangalore shows the value of Rs. 10,435/ha/day while the polluted wetland shows the value of Rs.20/ha/day. In contrast to this, Varthur, a sewage fed wetland has a value of Rs.118.9/ha/day. The pollutants and subsequent contamination of the wetland has telling effects such as disappearance of native species, dominance of invasive exotic species (such as African catfish), in addition to profuse breeding of disease vectors and pathogens. Water quality analysis revealed of high phosphates (4.22-5.76 ppm) level in addition to the enhanced BOD (119-140 ppm) and decreased DO (0-1.06 ppm). The amplified decline of ecosystem goods and services with degradation of water quality necessitates the implementation of sustainable management strategies to recover the lost wetland benefits.

Ecological and socio-economic assessment of Varthur wetland, Bengaluru (India)

Wetlands are the most productive ecosystems, recognized globally for its vital role in sustaining a wide array of biodiversity and provide goods and services. However despite their important role in maintaining the ecology and economy, wetlands in India are endangered by inattention and lack of appreciation for their role. Increased anthropogenic activities such as intense agriculture practices, indiscriminate disposal of industrial effluents and sewage wastes have altered the physical, chemical as well as biological integrity of the ecosystem. This has resulted in the ecological degradation, which is evident from the current ecosystem valuation of Varthur wetland. Global valuation of coastal wetland ecosystem shows a total of 14,785/ha US$ annual economic value. An earlier study of relatively pristine wetland in Bangalore shows the value of Rs. 10,435/ha/day while the polluted wetland shows the value of Rs.20/ha/day. In contrast to this, Varthur, a sewage fed wetland has a value of Rs.118.9/ha/day. The pollutants and subsequent contamination of the wetland has telling effects such as disappearance of native species, dominance of invasive exotic species (such as African catfish), in addition to profuse breeding of disease vectors and pathogens. Water quality analysis revealed of high phosphates (4.22-5.76 ppm) level in addition to the enhanced BOD (119-140 ppm) and decreased DO (0-1.06 ppm). The amplified decline of ecosystem goods and services with degradation of water quality necessitates the implementation of sustainable management strategies to recover the lost wetland benefits.

Dynamics of the Indian-Ocean oxygen minimum zones

In the Indian Ocean, mid-depth oxygen minimum zones (OMZs) occur in the Arabian Sea and the Bay of Bengal. The lower part of the Arabian-Sea OMZ (ASOMZ; below 400 m) intensifies northward across the basin; in contrast, its upper part (above 400 m) is located in the central/eastern basin, well east of the most productive regions along the western boundary. The Bay-of-Bengal OMZ (BBOMZ), although strong, is weaker than the ASOMZ. To investigate the processes that maintain the Indian-Ocean OMZs, we obtain a suite of solutions to a coupled biological/physical model. Its physical component is a variable-density, 6 1/2-layer model, in which each layer corresponds to a distinct dynamical regime or water-mass type. Its biological component has six compartments: nutrients, phytoplankton, zooplankton, two size classes of detritus, and oxygen. Because the model grid is non-eddy resolving (0.5 degrees), the biological model also includes a parameterization of enhanced mixing based on the eddy kinetic energy derived from satellite observations. To explore further the impact of local processes on OMZs, we also obtain analytic solutions to a one-dimensional, simplified version of the biological model. Our control run is able to simulate basic features of the oxygen, nutrient, and phytoplankton fields throughout the Indian Ocean. The model OMZs result from a balance, or lack thereof, between a sink of oxygen by remineralization and subsurface oxygen sources due primarily to northward spreading of oxygenated water from the Southern Hemisphere, with a contribution from Persian-Gulf water in the northern Arabian Sea. The northward intensification of the lower ASOMZ results mostly from horizontal mixing since advection is weak in its depth range. The eastward shift of the upper ASOMZ is due primarily to enhanced advection and vertical eddy mixing in the western Arabian Sea, which spread oxygenated waters both horizontally and vertically. Advection carries small detritus from the western boundary into the central/eastern Arabian Sea, where it provides an additional source of remineralization that drives the ASOMZ to suboxic levels. The model BBOMZ is weaker than the ASOMZ because the Bay lacks a remote source of detritus from the western boundary. Although detritus has a prominent annual cycle, the model OMZs do not because there is not enough time for significant remineralization to occur.

Integrating biodiversity and conservation with modern agricultural landscapes

To achieve food security and meet the demands of the ever-growing human populations, farming systems have assumed unsustainable practices to produce more from a finite land area. This has been cause for concern mainly due to the often-irreversible damage done to the otherwise productive agricultural landscapes. Agro-ecology is proclaimed to be deteriorating due to eroding integrity of connected ecological mosaics and vulnerability to climate change. This has contributed to declining species diversity, loss of buffer vegetation, fragmentation of habitats, and loss of natural pollinators or predators, which eventually leads to decline in ecosystem services. Currently, a hierarchy of conservation initiatives is being considered to restore ecological integrity of agricultural landscapes. However, the challenge of identifying a suitable conservation strategy is a daunting task in view of socio-ecological factors that may constrain the choice of available strategies. One way to mitigate this situation and integrate biodiversity with agricultural landscapes is to implement offset mechanisms, which are compensatory and balancing approaches to restore the ecological health and function of an ecosystem. This needs to be tailored to the history of location specific agricultural practices, and the social, ecological and environmental conditions. The offset mechanisms can complement other initiatives through which farmers are insured against landscape-level risks such as droughts, fire and floods. For countries in the developing world with significant biodiversity and extensive agriculture, we should promote a comprehensive model of sustainable agricultural landscapes and ecosystem services, replicable at landscape to regional scales. Arguably, the model can be a potential option to sustain the integrity of biodiversity mosaic in agricultural landscapes.

Infection of Human Endothelial Cells by Japanese Encephalitis Virus: Increased Expression and Release of Soluble HLA-E

Japanese encephalitis virus (JEV) is a single stranded RNA virus that infects the central nervous system leading to acute encephalitis in children. Alterations in brain endothelial cells have been shown to precede the entry of this flavivirus into the brain, but infection of endothelial cells by JEV and their consequences are still unclear. Productive JEV infection was established in human endothelial cells leading to IFN-beta and TNF-alpha production. The MHC genes for HLA-A, -B, -C and HLA-E antigens were upregulated in human brain microvascular endothelial cells, the endothelial-like cell line, ECV 304 and human foreskin fibroblasts upon JEV infection. We also report the release/shedding of soluble HLA-E (sHLA-E) from JEV infected human endothelial cells for the first time. This shedding of sHLA-E was blocked by an inhibitor of matrix metalloproteinases (MMP). In addition, MMP-9, a known mediator of HLA solubilisation was upregulated by JEV. In contrast, human fibroblasts showed only upregulation of cell-surface HLA-E. Addition of UV inactivated JEV-infected cell culture supernatants stimulated shedding of sHLA-E from uninfected ECV cells indicating a role for soluble factors/cytokines in the shedding process. Antibody mediated neutralization of TNF-alpha as well as IFNAR receptor together not only resulted in inhibition of sHLA-E shedding from uninfected cells, it also inhibited HLA-E and MMP-9 gene expression in JEV-infected cells. Shedding of sHLA-E was also observed with purified TNF-alpha and IFN-beta as well as the dsRNA analog, poly (I:C). Both IFN-beta and TNF-alpha further potentiated the shedding when added together. The role of soluble MHC antigens in JEV infection is hitherto unknown and therefore needs further investigation.

Advancing biodiversity research in developing countries: the need for changing paradigms

The world is in the midst of a biodiversity crisis, threatening essential goods and services on which humanity depends. While there is an urgent need globally for biodiversity research, growing obstacles are severely limiting biodiversity research throughout the developing world, particularly in Southeast Asia. Facilities, funding, and expertise are often limited throughout this region, reducing the capacity for local biodiversity research. Although western scientists generally have more expertise and capacity, international research has sometimes been exploitative ``parachute science,'' creating a culture of suspicion and mistrust. These issues, combined with misplaced fears of biopiracy, have resulted in severe roadblocks to biodiversity research in the very countries that need it the most. Here, we present an overview of challenges to biodiversity research and case studies that provide productive models for advancing biodiversity research in developing countries. Key to success is integration of research and education, a model that fosters sustained collaboration by focusing on the process of conducting biodiversity research as well as research results. This model simultaneously expands biodiversity research capacity while building trust across national borders. It is critical that developing countries enact policies that protect their biodiversity capital without shutting down international and local biodiversity research that is essential to achieve the long-term sustainability of biodiversity, promoting food security and economic development.

Infection of human amniotic and endothelial cells by Japanese encephalitis virus: Increased expression of HLA-F

Productive infection of human amniotic and endothelial cell lines with Japanese encephalitis virus (JEV) was established leading to the induction of NF kappa B and HLA-F, a non-classical MHC molecule. Induction of the HLA-F gene and protein in JEV-infected cells was shown to be NF kappa B dependent since it was blocked by inhibitors of NF kappa B activation. ShRNA targeting lentivirus-mediated stable knockdown of the p65 subunit of NF kappa B inhibited JEV-mediated induction of HLA-F both in the amniotic cell line, AV-3 as well as the human brain microendothelial cell line, HBMEC. The induction of HLA-F by treatment of AV-3 with TNF-alpha was also inhibited by ShRNA mediated knockdown of NF kappa B. TNF-alpha treatment of HEK293T cells that were transfected with reporter plasmids under the control of HLA-F enhancer A elements resulted in significant transactivation of the luciferase reporter gene. NF kappa B-mediated induction of HLA-F following JEV infection and TNF-alpha exposure is being suggested for the first time. (C) 2014 Elsevier Inc. All rights reserved.

Inhibition of ERK and proliferation in NK cell lines by soluble HLA-E released from Japanese encephalitis virus infected cells

Productive infection of human endothelial cells with Japanese encephalitis virus (JEV), a single stranded RNA virus induces shedding of sHLA-E. We show here that sHLA-E that is released upon infection with this flavivirus can inhibit IL-2 and PMA mediated ERK 1/2 phosphorylation in two NK cell lines, Nishi and NKL. Virus infected or IFN-gamma treated cell culture supernatants containing sHLA-E were found to partially inhibit IL-2 mediated induction of CD25 molecules on NKL cells. It was also found that sHLA-E could inhibit IL-2 induced H-3]-thymidine incorporation suggesting that, similar to cell surface expressed HLA-E, sHLA-E could also inhibit NK cell responses. Hence JEV-induced shedding of sHLA-E needs further investigation to better understand immune responses in JEV infections since it may have a role in viral evasion of NK cell responses. (C) 2014 Elsevier B.V. All rights reserved.