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The present study illustrates the design and synthesis of new series of 3-trifluoromethylpyrazole tethered chalcone-pyrrole and pyrazoline-pyrrole derivatives. All compounds were further screened for in vitro cytostatic activities on full NCI 60 cancer cell lines at National Cancer Institute, USA. Compounds (2E)-3-(1H-pyrrol-2-yl)-1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}prop-2-en-1-one ( 5a ) and (2E)-1-{3-methyl-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3-(1H-pyrrol-2-yl)prop-2-en-1-one ( 5c ) displayed significant antiproliferative activity (Growth Percentage: −77.10 and −92.13, respectively at 10 μM concentration) against the UO-31 cell lines from renal cancer and were further selected for assay at 10-fold dilutions of five different concentrations (10−4 to 10−8 M). Both compounds 5a and 5c exhibited promising antiproliferative activity (GI50: 1.36 to 0.27 μM) against leukemia cancer cell lines HL-60 and RPMI-8226, colon cancer cell lines KM-12; breast cancer cell lines BT-549. Moreover, both compounds 5a and 5c were found to be non-cytotoxic (LC50>100) against HL-60, RPMI-8226, and KM-12 cell lines. Remarkably, GI50 values of compounds 5a and 5c were identified as more promising than sunitinib against most cancer cell lines. In silico study of compounds 5a and 5c exemplified the desired ADME properties for drug-likeness as well as tighter interactions with VEGFR-2. Hence, compounds 5a and 5c would be good cytotoxic agents after further clinical study.  相似文献   
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MOTIVATION: Genome-wide experiments only rarely show resounding success in yielding genes associated with complex polygenic disorders. We evaluate 49 obesity-related genome-wide experiments with publicly available findings including microarray, genetics, proteomics and gene knock-down from human, mouse, rat and worm, in terms of their ability to rediscover a comprehensive set of genes previously found to be causally associated or having variants associated with obesity. RESULTS: Individual experiments show poor predictive ability for rediscovering known obesity-associated genes. We show that intersecting the results of experiments significantly improves the sensitivity, specificity and precision of the prediction of obesity-associated genes. We create an integrative model that statistically significantly outperforms all 49 individual genome-wide experiments. We find that genes known to be associated with obesity are significantly implicated in more obesity-related experiments and use this to provide a list of genes that we predict to have the highest likelihood of association for obesity. The approach described here can include any number and type of genome-wide experiments and might be useful for other complex polygenic disorders as well.  相似文献   
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OEIS is an extremely rare constellation of malformations, which includes omphalocele, exstrophy of cloaca, imperforate anus, and spinal defect. We report here autopsy findings in a case of OEIS complex, which apart from the major anomalies of the complex had bilateral club foot that is, congenital talipes equinovarus, right hydroureter, and body stalk anomaly. The umbilical cord was absent, and the umbilical vessels were embedded in an amniotic sheet, which connected the skin margin of the anterior body wall defect to the placenta, this feature being the hallmark of limb body wall complex (LBWC). This case further supports the view that OEIS and LBWC represent a continuous spectrum of abnormalities rather than separate conditions and may share a common etiology and pathogenetic mechanism as proposed by some authors.  相似文献   
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A comparative bioaccumulation pattern and ultra structural changes were studied in Phragmites cummunis, Typha angustifolia and Cyperus esculentus in mixed metals solution of cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn). P. cummunis was observed to be a shoot accumulator for Cr, Fe, Mn, Ni, Pb, and Zn. However, T. angustifolia was found to be a root accumulator for Cd, Cr, Cu, Fe, Ni and Pb. In addition, C. esculentus also accumulated most of the tested heavy metals in the roots, while Mn and Fe were translocated up to leaves. Further, the long term metal treatment showed maximum accumulation of all heavy metals in P. cummunis followed by T. angustifolia and C. esculentus. Among heavy metals, Fe was accumulated maximum, i.e., >1000 microg g(-1) by all three plants. Simultaneously, the adverse effects on biochemical parameters were noted earlier in C. esculentus than T. angustifolia and P. cummunis. Ultra structural observation showed the cellular changes in wetland plants after longer exposure. Results revealed that P. cummunis and T. angustifolia had more potential for tested metals than C. esculentus. This study established that these wetland plants could be used for heavy metals phytoremediation from metal containing industrial wastewater.  相似文献   
5.
Interleukin-10 (IL10), an anti-inflammatory cytokine, has been implicated in a variety of immune- and inflammatory-related diseases. We investigated the following SNPs: -1082, -819, -592 in the promoter region of IL10 in a normal (control) population and selected diseases: breast cancer (BrCa), systemic lupus erythematosus (SLE), and B-cell chronic lymphocytic leukemia (B-CLL) by denaturing high-performance liquid chromatography (DHPLC) and found distinct genotype and haplotype patterns. DHPLC was performed using the Transgenomic WAVE instrument, a mutational discovery tool that allows for high throughout analysis of SNPs. The principle of DHPLC is based on separation of homo- and heteroduplex formation of individual polymerase chain reaction products at specific melting temperatures and set gradients. The melting temperature selected for each SNP was based on size and sequence of the polymerase chain reaction product (for -1082, 57 degrees C; for -819, 58 degrees C; and for -592, 59.2 degrees C). Before fragment mutational analysis, all samples were denatured at 95 degrees C and slowly reannealed to allow for reassociation of different strands. Heteroduplex samples were easily distinguished from homoduplex samples. In order to identify wild type from homozygous mutant, two homoduplex polymerase chain reaction samples had to be mixed together, denatured at 95 degrees C and reannealed. The homozygous mutant, when combined with wild type, displayed a double peak on chromatogram. Once distinct chromatograms were established for each of the SNPs and the nucleotide changes confirmed by sequencing, genotype and haplotype frequencies were tabulated for the groups studied.  相似文献   
6.
This study deals with the optimization of bacterial degradation of pyridine raffinate by previously isolated two aerobic bacteria ITRCEM1 (Bacillus cereus) and ITRCEM2 (Alcaligens faecalis) with accession number DQ4335020 and DQ435021, respectively. The degradation of pyridine raffinate was studied by axenic and mixed bacterial consortium at different nutritional and environmental conditions after the removal of formaldehyde from pyridine raffinate (FPPR). Results revealed that the optimum degradation of pyridine raffinate was observed by mixed bacterial culture in presence of glucose (1% w/v) and peptone (0.2% w/v) at 20% FPPR, pH 7.0, temperature 30°C and 120 rpm at 168 h incubation period . The HPLC analysis of degraded pyridine raffinate samples has indicated the complete removal of α, β and γ picoline. Further, the GC–MS analysis of FPPR pyridine raffinate has shown the presence of pyrazine acetonitrile (6.74), 1,3-dioxepin (8.68), 2-pyridine carboxaldehyde (11.26), propiolactone (12.06), 2-butanol (13.10), benzenesulfonic acid (16.22) and 1,4-dimethyl pyperadine while phenol (17.64) and 3,4-dimethyl benzaldehyde as metabolic products of FPPR.  相似文献   
7.
Papaya leaf curl disease (PaLCuD) caused by papaya leaf curl virus (PaLCuV) not only affects yield but also plant growth and fruit size and quality of papaya and is one of the most damaging and economically important disease. Management of PaLCuV is a challenging task due to diversity of viral strains, the alternate hosts, and the genomic complexities of the viruses. Several management strategies currently used by plant virologists to broadly control or eliminate the viruses have been discussed. In the absence of such strategies in the case of PaLCuV at present, the few available options to control the disease include methods like removal of affected plants from the field, insecticide treatments against the insect vector (Bemisia tabaci), and gene-specific control through transgenic constructs. This review presents the current understanding of papaya leaf curl disease, genomic components including satellite DNA associated with the virus, wide host and vector range, and management of the disease and suggests possible generic resistance strategies.  相似文献   
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