22 research outputs found

    Geotechnical Aspects of Recent Extreme Floods in Pakistan; A Case History

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    Topographically, Pakistan comprises three major areas; Northern Highland Area, Indus Basin and Baluchistan Plateau. Its elevation varies from Mean sea Level (0 meter) at south to 8619 meters in the North at K-2 Peak. Northern Highland Area, generally sloping southwards includes Himalayan, Karakorum and Hindu-Kush ranges covering approximately an area of 155,831 square kilometers. Indus Basin stretches from foothills of Northern Highland Area to Arabian Sea in south covering approximately an area of 346,259 square kilometers. Baluchistan Plateau in the West and South comprises mountain ranges of Koh-i-Suleman, Kirther, blow-outs of coralline and lacustrine deposits along coastal belt and covers approximately an area of 347,190 square kilometers. Climate of the country varies from tropical to temperate with rain fall variation of as little as 10 inches a year in South to 150 inches a year in the North. Any rainfall surges in the North frequently unleash floods along the Indus Basin. Continuous deforestation and fires in Northern Highland Area, growing housing projects alongside water channels in the backdrop of global warming and climate change has enhanced frequency and severity of floods in Pakistan. The year 2010 witnessed the worst flood in the history of Pakistan. The causal factors of this rare event are attributed to the amalgamation of two weather systems over Hindu-Kush and Karakorum ranges in the North. The resulting outburst in the realm of denuded landforms graduating from North to South brought about the hydrological extremes never seen before. The event was accompanied with landslides along the slopes washing away numerous houses, over-flowing water channels destroying habitats in the flood plains, precious crops, bridges, and endangered barrages and dams. While scars of a little less similar phenomenon in year 1992 due to cloud burst in Kashmir are still visible on the face of Nation, this flood caused 1985 deaths, 2946 injured; 20 million people were left homeless and destroyed 2.2 million hectares of cropped area, while damage to communication infrastructure is estimated in billions of dollars. The study encompasses geotechnical aspects of landform distribution, climatic changes and hydrological responses

    Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles

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    Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium-doped nanoparticles coated with lectins and antibodies to identify a biomarker combination consisting of integrin subunit alpha 3 (ITGA3) and fucose. In addition, we used the same cancer cell line-derived EVs as analytical standards to assess the sensitivity of the ITGA3-UEA assay. The clinical performance of the ITGA3-UEA assay was analysed using urine samples of various urological pathologies including diagnostically challenging benign prostatic hyperplasia (BPH), prostate cancer (PCa) and bladder cancer (BlCa). The assay can significantly discriminate BlCa from all other patient groups: PCa (9.2-fold; p = 0.00038), BPH (5.5-fold; p = 0.004) and healthy individuals (and 23-fold; p = 0.0001). Our results demonstrate that aberrantly fucosylated uEVs and integrin ITGA3 can be detected with fucose-specific lectin UEA in a simple bioaffinity assay for the detection of BlCa directly from unprocessed urine.</p

    CRISPR Interference (CRISPRi) Inhibition of luxS Gene Expression in E. coli: An Approach to Inhibit Biofilm

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    Biofilm is a sessile bacterial accretion embedded in self-producing matrix. It is the root cause of about 80% microbial infections in human. Among them, E. coli biofilms are most prevalent in medical devices associated nosocomial infections. The objective of this study was to inhibit biofilm formation by targeting gene involved in quorum sensing, one of the main mechanisms of biofilm formation. Hence we have introduced the CRISPRi, first time to target luxS gene. luxS is a synthase, involved in the synthesis of Autoinducer-2(AI-2), which in turn guides the initial stage of biofilm formation. To implement CRISPRi system for luxS gene suppression, we have synthesized complementary sgRNA to target gene sequence and co-expressed with dCas9, a mutated form of an endonuclease. Suppression of luxS expression was confirmed through qRT-PCR. The effect of luxS gene on biofilm inhibition was studied through crystal violet assay, XTT reduction assay and scanning electron microscopy. We conclude that CRISPRi system could be a potential strategy to inhibit bacterial biofilm through mechanism base approach

    Antibiofilm action of a toluidine blue O-silver nanoparticle conjugate on <i>Streptococcus mutans</i>: a mechanism of type I photodynamic therapy

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    <p>The objective of this study was to evaluate the anti-biofilm efficacy of photodynamic therapy by conjugating a photosensitizer (TBO) with silver nanoparticles (AgNP). <i>Streptococcus mutans</i> was exposed to laser light (630 nm) for 70 s (9.1 J cm<sup>−2</sup>) in the presence of a toluidine blue O–silver nanoparticle conjugate (TBO–AgNP). The results showed a reduction in the viability of bacterial cells by 4 log<sub>10</sub>. The crystal violet assay, confocal laser scanning microscopy and scanning electron microscopy revealed that the TBO–AgNP conjugates inhibited biofilm formation, increased the uptake of propidium iodide and leakage of the cellular constituents, respectively. Fluorescence spectroscopic studies confirmed the generation of OH<sup><i>•</i></sup> as a major reactive oxygen species, indicating type I phototoxicity. Both the conjugates down-regulated the expression of biofilm related genes compared to TBO alone. Hence TBO–AgNP conjugates were found to be more phototoxic against <i>S. mutans</i> biofilm than TBO alone.</p

    Lectins as potential tools for cancer biomarker discovery from extracellular vesicles

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    Abstract Extracellular vesicles (EVs) have considerable potential as diagnostic, prognostic, and therapeutic agents, in large part because molecular patterns on the EV surface betray the cell of origin and may also be used to “target” EVs to specific cells. Cancer is associated with alterations to cellular and EV glycosylation patterns, and the surface of EVs is enriched with glycan moieties. Glycoconjugates of EVs play versatile roles in cancer including modulating immune response, affecting tumor cell behavior and site of metastasis and as such, paving the way for the development of innovative diagnostic tools and novel therapies. Entities that recognize specific glycans, such as lectins, may thus be powerful tools to discover and detect novel cancer biomarkers. Indeed, the past decade has seen a constant increase in the number of published articles on lectin-based strategies for the detection of EV glycans. This review explores the roles of EV glycosylation in cancer and cancer-related applications. Furthermore, this review summarizes the potential of lectins and lectin-based methods for screening, targeting, separation, and possible identification of improved biomarkers from the surface of EVs
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