IL-17A promotes intracellular growth of Mycobacterium by inhibiting apoptosis of infected macrophages

The fate of infected macrophages is a critical aspect of immunity to mycobacteria. By depriving the pathogen of its intracellular niche, apoptotic death of the infected macrophage has been shown to be an important mechanism to control bacterial growth. Here, we show that IL-17 inhibits apoptosis of Mycobacterium bovis BCG- or Mycobacterium tuberculosis-infected macrophages thus hampering their ability to control bacterial growth. Mechanistically, we show that IL-17 inhibits p53, and impacts on the intrinsic apoptotic pathway, by increasing the Bcl2 and decreasing Bax expression, decreasing cytochrome c release from the mitochondria, and inhibiting caspase-3 activation. The same effect of IL-17 was observed in infected macrophages upon blockade of p53 nuclear translocation. These results reveal a previously unappreciated role for the IL-17/p53 axis in the regulation of mycobacteria-induced apoptosis and can have important implications in a broad spectrum of diseases where apoptosis of the infected cell is an important host defense mechanism.Fundação para a Ciência e Tecnologia, Portugal. Project grants: PTDC/SAU-MII/101977/2008 (to AGC), PTDC/BIA-BCM/102776/2008 (to MS) and HMSP-ICT/0024/2010 (to RA) and co-funded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER). Personal Grants: SFRH/BPD/33036/2006 to AC; SFRH/BD/33573/200

Design and fabrication of single cylinder diesel engine for bio-diesel

Modification of diesel engine is the current trend in automobile industries. The limitations of fossil fuel as well as global warming, time has come to use alternative fuels in diesel engines to meet the energy demand globally. For using bio diesel the terminologies of the diesel engine has been changed. Some of the terminologies are fuel injection pump, injection nozzle. These terminologies were modified for better Specific fuel consumption and Brake thermal efficiency.The higher the fuel injection pressure, the better the atomization of the fuel. A better atomization of the fuel leads to a better combustion characteristics. This implies better performance, higher power and lower emission. The objective of our project is to fabricate and run the modified bio diesel engine and calculating the brake thermal efficiency and specific fuel consumption of the modified bio diesel engine

Antimicrobial Behavior of Biosynthesized Silica-Silver Nanocomposite for Water Disinfection: A Mechanistic Perspective

The biosynthesis of nano-silica silver nanocomposite (NSAgNC) and it’s as antibacterial effect on gram-negative bacteria viz. Escherichia coli and Pseudomonas aeruginosa has been investigated for disinfection of water. The as-synthesized NSAgNC exhibited antibacterial activity in a dose dependent manner and ~99.9% of E. coli and P. aeruginosa were killed at a concentration of 1.5 mg/mL of NSAgNC (5.1 wt% Ag) within 5 h. The NSAgNC showed similar antibacterial activities both in oxic and anoxic conditions. The results further demonstrated that NSAgNC exhibited reactive oxygen species (ROS) independent “particle specific” antibacterial activity through multiple steps in absence of leached out Ag+ ions. The initial binding of NSAgNC on the cell wall caused loss of cell membrane integrity and leakage of cytoplasmic materials. Inhibition of respiratory chain dehydrogenase by NSAgNC caused metabolic inactivation of the cells and affecting the cell viability. Genomic and proteomic studies further demonstrated the fragmentations of both plasmid and genomic DNA and down regulation of protein expression in NSAgNC treated cells, which leading to the cell death. Thus the biosynthesized NSAgNC has great potential as disinfectant for water purification while minimizing the toxic effects

The Impacts of Climate and Land Use Change on Mojave Desert Tortoise (Gopherus agassizii) Habitat Suitability and Landscape Genetic Connectivity

The Mojave desert in the southwestern United States faces a multitude of anthropogenic stressors including urbanization, population growth, solar energy development, expansion of transportation infrastructure and military training, as well as climate change that has impacted the region through habitat fragmentation and altered precipitation and temperature regimes. The Mojave desert tortoise is a species that persists on this landscape despite these impacts that could influence its long-term population densities, distributions, and connectivity.A fundamental goal of conservation prioritization is understanding the distribution of suitable habitat and maintaining connected landscapes between these habitats to ensure species can adapt to changes in their environments. Species distribution models identify regions of suitable habitat based on statistical modeling relating location data for the species to environmental variables that influence the distribution of the species. Examining how landscape features, specifically landscape composition and configuration, interact with microevolutionary processes such as gene flow helps identify which landscape features facilitate or limit gene flow and subsequently connectivity for a species. In this dissertation I sought to understand how the compounded effects of land use and climate change would impact habitat suitability and landscape connectivity at multiple temporal and spatial scales for the tortoise using various spatial and genetic tools. In chapter 1 I created a sampling design to guide targeted field efforts to obtain location and genetic data focused on under-surveyed edge regions of the tortoise’s range. I used this sampling design to obtain new genetic samples and used the new dataset to determine the efficacy of my initial design as well as examine whether my new samples represented new climatic niches. In chapter 2 I built a range-wide habitat suitability model for the tortoise and forecasted this model to climate and land use change scenarios. I also explored the influence of scale by building regional habitat suitability models and forecasting these models. I found that precipitation, temperature, and soil variables influence habitat suitability at range-wide scales and the direction of these relationships changed at the regional scale. Forecast models predicted widespread loss of tortoise habitat under all future scenarios, with the highest net change in habitat across critical habitat units for the species, and least net change across military bases. Habitat was shifted northward over time, with the southern edge losing the most amount of habitat by the worst-case climate and land use scenarios in 2098. In chapter 3 I used a range-wide genomics dataset to estimate population structure and to build habitat-based connectivity models using isolation-by-resistance (IBR) approaches at various temporal scales. I found that as habitat availability declined in the southern edge of the range, there was a concomitant loss of connectivity, and that connectivity was also gained in the northern edge of the range. I used comparative modeling in a maximum likelihood population effects (MLPE) framework and found that IBR based metrics were the best predictors of range-wide connectivity, indicating that habitat features on the landscape drive genetic differentiation and gene flow for the tortoise. Overall, this work creates a novel sampling design methodology as well as identifies the impacts of climate and land use on tortoise habitat and connectivity using multiple approaches. This research identifies specific tortoise habitat and connective corridors, in vulnerable regions such as the southern and central range, that should continue to be protected to ensure persistence of the species currently as well as into the future

Using a Habitat Suitability Model and Molecular Analyses to Aid in the Conservation Management of the Texas tortoise, Gopherus berlandieri

The Texas tortoise, Gopherus berlandieri (Agassiz 1857), is a threatened species in the state of Texas and strict conservation action is required to ensure that continuing population decline does not occur. The historical range of the Texas tortoise includes a much larger area than recent observations support. Assessing the habitat suitability of the eastern portion of the historical range of the species and determining whether this region still supports the species will aid in its conservation. Firstly, road surveys were conducted from March to October of 2014 and seven tortoises were found during this period. None of these tortoises were from the eastern portion of the range that was the focus of the surveys. GPS coordinates of tortoises from these surveys along with coordinates obtained from online databases were used with environmental predictors to model habitat suitability for the species using ArcGIS (v10.2) and Maxent (v3.3.k). I found that there are some patches of habitat in the eastern portion that could potentially support the species. In addition, I found areas of suitability in far south Texas, as well as in the northern and western regions of their historical range. Secondly, 22 molecular markers in the form of microsatellite loci that were previously found to amplify in G. polyphemus, were re-tested for cross-amplification in G. berlandieri. Nineteen out of the 22 loci cross-amplified successfully. Seven additional untested markers were further focused on and I found that four of the seven were polymorphic, and had variable levels of allelic richness. I then performed a population genetics analysis using STRUCTURE v2.3.4 to determine whether tortoises found out of their range fell into a known subpopulation to allow for repatriation and this indicated that G. berlandieri has no segregation into multiple populations or clusters. This might be due to low sample size and less markers used or an artifact of most samples being from the same area. These studies attempt to explain the poorly understood factors of habitat suitability, and aid genetic diversity research for the Texas tortoise. This in turn will allow for better management and conservation of the species throughout its range.Biolog

Cell death paradigms in the pathogenesis of Mycobacterium tuberculosis infection

Cell death or senescence is a fundamental event that helps maintain cellular homeostasis, shapes the growth of organism, and provides protective immunity against invading pathogens. Decreased or increased cell death is detrimental both in infectious and non infectious diseases. Cell death is executed both by regulated enzymic reactions and non enzymic sudden collapse. In this brief review we have tried to summarize various cell death modalities and their impact on the pathogenesis of Mycobacterium tuberculosi