Significant Role of Segmental Duplications and SIDD Sites in Chromosomal Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic Analysis.

Recurrent non-random chromosomal translocations are hallmark characteristics of leukemogenesis, and however, molecular mechanisms underlying these rearrangements are less explored. The fundamental question is, why and how chromosomes break and reunite so precisely in the genome. Meticulous understanding of mechanism leading to chromosomal rearrangement can be achieved by characterizing breakpoints. To address this hypothesis, a novel multi-parametric computational approach for characterization of major leukemic translocations within and around breakpoint region was performed. To best of our knowledge, this bioinformatic analysis is unique in finding the presence of segmental duplications (SDs) flanking breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were analyzed for stress-induced duplex destabilization (SIDD) sites along with other complex genomic architecture and physicochemical properties. Our study distinctly emphasizes on the probable correlative role of SDs, SIDD sites and various genomic features in the occurrence of breakpoints. Further, it also highlights potential features which may be playing a crucial role in causing double-strand breaks, leading to translocation.

Current drugs and drug targets in non-small cell lung cancer: limitations and opportunities.

Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced in the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

Characterization of chromosomal translocation breakpoint sequences in solid tumours: "an in silico analysis".

Chromosomal translocations that results in formation and activation of fusion oncogenes are observed in numerous solid malignancies since years back. Expression of fusion kinases in these cancers drives the initiation & progression that ultimately leads to tumour development and thus comes out to be clinically imperative in terms of diagnosis and treatment of cancer. Nonetheless, molecular mechanisms beneath these translocations remained unexplored consequently limiting our knowledge of carcinogenesis and hence is the current field where further research is required. The issue of prime focus is the precision with which the chromosomes breaks and reunites within genome. Characterization of Genomic sequences located at Breakpoint region may direct us towards the thorough understanding of mechanism leading to chromosomal rearrangement. A unique computational multi-parametric analysis was performed for characterization of genomic sequence within and around breakpoint region. This study turns out to be novel as it reveals the occurrence of Segmental Duplications flanking the breakpoints of all translocation. Breakpoint Islands were also investigated for the presence of other intricate genomic architecture and various physico-chemical parameters. Our study particularly highlights the probable role of SDs and specific genomic features in precise chromosomal breakage. Additionally, it pinpoints the potential features that may be significant for double-strand breaks leading to chromosomal rearrangements.

Treatment of beet sugar wastewater by UAFB bioprocess.

The aim of this work was to study the treatment of strong beet sugar wastewater by an upflow anaerobic fixed bed (UAFB) at pilot plant scale. Three fixed bed bioreactors (each 60 L) were filled with standard industrial packing, inoculated with anaerobic culture (chicken manure, cow manure, anaerobic sludge digested from domestic wastewater) and operated at 32-34 degrees C with 20 h hydraulic retention time (HRT) and influent COD ranging between 2000-8000 mg/L. Under these conditions the maximum efficiency of organic content reduction in the reactor ranged from 75% to 93%. The reactor filled with standard pall rings made of polypropylene with an effective surface area of 206 m(2)/m(3) performed best in comparison to the reactor filled with cut polyethylene pipe 134 m(2)/m(3) and reactor filled with PVC packing (50 m(2)/m(3)). There was 2-7% decrease in efficiency with PE while it was 10-16% in case of PVC when compared to standard pall rings. The study provided a very good basis for comparing the effect of packing in reduction efficiency of the system.

Bioremediation of toxic heavy metals using acidothermophilic autotrophes.

Investigations were carried out to isolate microbial strains from soil, mud and water samples from metallurgically polluted environment for bioremediation of toxic heavy metals. As a result of primary and secondary screening various 72 acidothermophilic autotrophic microbes were isolated and adapted for metal tolerance and biosorption potentiality. The multi-metal tolerance was developed with higher gradient of concentrations of Ag, As, Bi, Cd, Cr, Co, Cu, Hg, Li, Mo, Pb, Sn and Zn. The isolates were checked for their biosolubilization ability with copper containing metal sulfide ores. In case of chalcopyrite 85.82% and in covellite as high as 97.5% copper solubilization occurred in presence of 10(-3) M multi-heavy metals on fifth day at 55 degrees C and pH 2.5. Chemical analyses were carried out by inductively coupled plasma spectroscopy (ICP) for metal absorption. The selected highly potential isolate (ATh-14) showed maximum adsorption of Ag 73%, followed by Pb 35%, Zn 34%, As 19%, Ni 15% and Cr 9% in chalcopyrite.

Screening of thermoacidophilic autotrophic bacteria for covellite solubilization.

In an attempt to obtain suitable bacterial isolates for bioleaching of copper from chalcopyrite and covellite, soil samples taken from areas of the metal industry were screened using an enrichment procedure specially run at acidic pH and thermophilic temperature range, to overcome the limitations of mesophiles employed for the purpose besides having economic and environmental advantages. Of a total of 47 isolates, the most promising 3 having resistance to copper toxicity were evolved by subjecting them to gradually increasing concentrations of CuSO4 by acclimatization runs conducted on an environmental shaker for 125 d at 65 degrees C. The isolates, JVCu-8, JVCu-10, and JVCu-12, exhibited significantly enhanced bioleaching and copper tolerance ability at pH 3.5 and 60-70 degrees C. The total solubilization of copper recorded was 87, 89.4, and 91.2% by JVCu-8, JVCu-10, and JVCu-12, respectively, and these isolates exhibited tolerance to CuSO4 concentrations of 6.9, 7.2, and 7.2%, respectively. The isolates morphologically resembled Thiobacillus and Sulfolobus.