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71.
Identification of biological relationships from text documents using efficient computational methods
Palakal M Stephens M Mukhopadhyay S Raje R Rhodes S 《Journal of bioinformatics and computational biology》2003,1(2):307-342
The biological literature databases continue to grow rapidly with vital information that is important for conducting sound biomedical research and development. The current practices of manually searching for information and extracting pertinent knowledge are tedious, time-consuming tasks even for motivated biological researchers. Accurate and computationally efficient approaches in discovering relationships between biological objects from text documents are important for biologists to develop biological models. The term "object" refers to any biological entity such as a protein, gene, cell cycle, etc. and relationship refers to any dynamic action one object has on another, e.g. protein inhibiting another protein or one object belonging to another object such as, the cells composing an organ. This paper presents a novel approach to extract relationships between multiple biological objects that are present in a text document. The approach involves object identification, reference resolution, ontology and synonym discovery, and extracting object-object relationships. Hidden Markov Models (HMMs), dictionaries, and N-Gram models are used to set the framework to tackle the complex task of extracting object-object relationships. Experiments were carried out using a corpus of one thousand Medline abstracts. Intermediate results were obtained for the object identification process, synonym discovery, and finally the relationship extraction. For the thousand abstracts, 53 relationships were extracted of which 43 were correct, giving a specificity of 81 percent. These results are promising for multi-object identification and relationship finding from biological documents. 相似文献
72.
SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells 总被引:15,自引:0,他引:15
Chauhan D Pandey P Hideshima T Treon S Raje N Davies FE Shima Y Tai YT Rosen S Avraham S Kharbanda S Anderson KC 《The Journal of biological chemistry》2000,275(36):27845-27850
Our previous studies have shown that activation of a related adhesion focal tyrosine kinase (RAFTK) (also known as Pyk2) is required for dexamethasone (Dex)-induced apoptosis in multiple myeloma (MM) cells and that human interleukin-6 (IL-6), a known growth and survival factor for MM cells, blocks both RAFTK activation and apoptosis induced by Dex. However, the mechanism whereby IL-6 inhibits Dex-induced apoptosis is undefined. In this study, we demonstrate that protein-tyrosine phosphatase SHP2 mediates this protective effect. We show that IL-6 triggers selective activation of SHP2 and its association with RAFTK in Dex-treated MM cells. SHP2 interacts with RAFTK through a region other than its Src homology 2 domains. We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM. 相似文献
73.
Random amplification of polymorphic DNA polymerase chain reaction (RAPD-PCR) and pathological, morphological and ultrastructural characterization were used to differentiate seven new microsporidian isolates infecting the mulberry silkworm, Bombyx mori. The pathogenicity observed was dose-dependent and differed from each of the microsporidian isolates; the NIK-4m was found to be more virulent than other isolates. However, all the isolates, except NIK-4m, showed heavy gonadal infection and vertical transmission in the infected silkworms. Differences in the spore shape ranging from oval to elongate were observed, and the polar filament has 8-16 coils arranged in one or two rows. Of the 80 decamer random primers tested, 50 generated reproducible RAPD profiles and yielded a total of 600 fragments, of which 594 were polymorphic (99%). Forty nine RAPD primers produced 179 unique genetic markers, whose presence or absence differed among the microsporidians, albeit with varied efficiency of polymorphism detection. The degree of band sharing was used to evaluate genetic distances between different microsporidian isolates and to construct a phylogenetic tree using Dice coefficients. Cluster analysis based on Dice coefficients resulted in the formation of one major cluster consisting of NIK-1s, NIAP-7g, NIK-2r and NIK-5d and NIK-4m in the other; while NIAP-6p was intermediate between these two. NIK-8b and NITN-9n were found to be entirely different from others. Reproducible RAPD patterns of all microsporidian isolates enabled us to differentiate the microsporidian isolates. The results demonstrate that besides ultrastructural studies, RAPD-PCR can be a useful and reliable tool to detect polymorphism, genetic relationships, and for the identification of the microsporidians. In addition, DNA fingerprints generated in this process have potential applications as diagnostic tools for identification of different microsporidia with considerable accuracy. 相似文献
74.
Singh I Knezevic N Ahmmed GU Kini V Malik AB Mehta D 《The Journal of biological chemistry》2007,282(11):7833-7843
RhoA activation and increased intracellular Ca(2+) concentration mediated by the activation of transient receptor potential channels (TRPC) both contribute to the thrombin-induced increase in endothelial cell contraction, cell shape change, and consequently to the mechanism of increased endothelial permeability. Herein, we addressed the possibility that TRPC signals RhoA activation and thereby contributes in actinomyosin-mediated endothelial cell contraction and increased endothelial permeability. Transduction of a constitutively active Galphaq mutant in human pulmonary arterial endothelial cells induced RhoA activity. Preventing the increase in intracellular Ca2+ concentration by the inhibitor of Galphaq or phospholipase C and the Ca2+ chelator, BAPTA-AM, abrogated thrombin-induced RhoA activation. Depletion of extracellular Ca2+ also inhibited RhoA activation, indicating the requirement of Ca2+ entry in the response. RhoA activation could not be ascribed to storeoperated Ca2+ (SOC) entry because SOC entry induced with thapsigargin or small interfering RNA-mediated inhibition of TRPC1 expression, the predominant SOC channel in these endothelial cells, failed to alter RhoA activity. However, activation of receptor-operated Ca2+ entry by oleoyl-2-acetyl-sn-glycerol, the membrane permeable analogue of the Galphaq-phospholipase C product diacylglycerol, induced RhoA activity. Receptor-operated Ca2+ activation was mediated by TRPC6 because small interfering RNA-induced TRPC6 knockdown significantly reduced Ca2+ entry. TRPC6 knockdown also prevented RhoA activation, myosin light chain phosphorylation, and actin stress fiber formation as well as inter-endothelial junctional gap formation in response to either oleoyl-2-acetyl-sn-glycerol or thrombin. TRPC6-mediated RhoA activity was shown to be dependent on PKCalpha activation. Our results demonstrate that Galphaq activation of TRPC6 signals the activation of PKCalpha, and thereby induces RhoA activity and endothelial cell contraction. 相似文献
75.
76.
The present study was conducted to see the role of NF-kappaB in virulent (Mycobacterium tuberculosis H37Rv) and avirulent (M. tuberculosis H37Ra) mycobacterial infection in THP-1 cells. To inactivate NF-kappaB, pCMV-IkappaBalphaM dn containing THP-1 cell line was generated which showed marked increase in apoptosis with M. tuberculosis H37Rv and M. tuberculosis H37Ra. Infected THP-1-IkappaBalphaM dn cells showed decrease in mitochondrial membrane potential, cytochrome c release, activation of caspase-3 and enhanced TNF-alpha production. Increase in apoptosis of infected THP-1-IkappaBalphaM dn cells resulted in inhibition of intracellular mycobacterial growth. Differential NF-kappaB activation potential was observed with M. tuberculosis H37Rv and M. tuberculosis H37Ra. Both the strains activated NF-kappaB after 4 h in THP-1 cells however after 48 h only M. tuberculosis H37Rv activated NF-kappaB which lead to up-regulation of bcl-2 family anti-apoptotic member, bfl-1/A1. Our results indicated that NF-kappaB activation may be a determinant factor for the success of virulent mycobacteria within macrophages. 相似文献
77.
Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. 总被引:6,自引:0,他引:6
Diclofenac (DCLF) is a nonsteroidal anti-inflammatory drug that is widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute muscle pain conditions. Toxic doses of DCLF can cause nephrotoxicity in humans and experimental animals. However, whether this DCLF-induced nephrotoxicity involves apoptotic cell death in addition to necrosis is unknown. The goals of this investigation were to determine whether DCLF-induced nephrotoxicity involves oxidative stress and apoptotic type genomic DNA fragmentation, and if so, whether DCLF-induced oxidative stress and DNA fragmentation cause apoptotic cell death in mouse kidneys. Male ICR mice (CD-1; 25-45 g), fed ad libitum, were administered nephrotoxic doses of DCLF (100, 200, 300 mg/Kg, po) and sacrificed 24 h later. Blood was collected to evaluate renal injury (BUN), lipid peroxidation (MDA: malondialdehyde levels), and superoxide dismutase (SOD) activity (a marker of oxidative stress). Kidney tissues were analyzed both quantitatively and qualitatively to determine the degree and type of DNA damage, and evaluated histopathologically for the presence of apoptotic characteristics in the nucleus of diverse types of kidney cells. Results show that diclofenac is a powerful nephrotoxicant (at 100, 200, and 300 mg/kg: 4.7-, 4.9-, and 5.0-fold increases in BUN compared to the control, respectively) and a strong inducer of oxidative stress (significant increase in MDA levels). Oxidative stress induced by DCLF was also coupled with massive kidney DNA fragmentation (100, 200, and 300 mg/kg: 3-, 8-, and 10-fold increases compared to control, respectively). A dose-dependent increase in MDA levels and SOD activity was also observed, which indicated a link between oxidative stress and nephrotoxicity. Qualitative analysis of DNA fragmentation by gel electrophoresis showed a DNA ladder indicative of Ca2+-Mg2+-endonuclease activation. Histopathological examination of kidney sections revealed numerous apoptotic nuclei across proximal and distal tubular cell linings. Collectively, these data for the first time suggest that DCLF-induced nephrotoxicity may involve production of reactive oxygen species leading to oxidative stress and massive genomic DNA fragmentation, and these two free radical mediated events may ultimately translate into apoptotic cell death of kidney cells in vivo, and reveal a DNA-active role for DCLF. 相似文献
78.
Though the GroEL and DnaK heat shock proteins are well characterized in prokaryotes, only scanty and controversial information exist about their cellular localization. In the present study, the localization of the heat shock proteins DnaK and GroEL in normal and heat shocked cells of Vibrio cholerae, was investigated both by immunogold labeling of ultrathin sections and biochemical methods. Much of the DnaK was found to be localized at the inner membrane in unstressed cells, most probably at the Bayer's adhesion sites. Data suggested that upon heat shock, the DnaK associated with the membrane continued to remain there, but the newly synthesized DnaK appeared mostly in the cytoplasm. GroEL in both stressed and unstressed cells was found mainly in the cytoplasm. 相似文献
79.
Uttam Kumar Sarkar Prashant Kumar Deepak Raje Singh Negi Shriprakash Singh Dhurendra Kapoor 《Biodiversity and Conservation》2006,15(11):3579-3589
Over the last few decades wild population of Chitala chitala (HamiltonBuchanan) has been declined more than 50% due to various reasons and is presently listed under endangered (EN) category
due to reduced abundance. In the present communication wild C. chitala were collected from natural habitats and induced to spawn under captivity during July 2002 by injecting three different doses
of synthetic hormone Ovaprim. Intramuscular injections were administered to fishes using three different doses (1.5, 1.0 and
0.5 ml/kg body weight). Artificial breeding pool was prepared for each set by encircling area (20 × 5 m) with mosquito net,
where wooden country boat (8 × 4 × 2.5 feet with surface area 48.5 sq. feet) was placed inside the breeding pool. Distinct
spawning behavior was noticed in the experimental sets with different hormonal dose whereas no spawning activity was noticed
in control set. The fertilization rate varied from 48.8680.2% and total numbers of spawned eggs in two sets of experiments
were estimated to be 81,034. The average number of eggs deposited 15 ± 2.1/square inches. The fertilized eggs were large in
size (4.5 ± 0.05 mm), adhesive and attached to the hard substratum. The eggs hatch out between 168192 h after fertilization
and about 33,639 hatchlings were produced. Newly hatched larvae measured 10.23 ± 0.03 mm and 0.031± 0.008 gm in weight and
the mean diameter of yolk sac was 4.1 ± 0.08 mm. The yolk sac remains attached up to a week. The percentage survival of hatchlings
varied from 42.2 to 65.60. Statistical analysis was worked out to determine the relation between the hormone dosage with different
breeding parameters like latency period, fertilization rate, egg output, hatching rate and hatchling production. 相似文献
80.
为了获得印度北部赣达(Ganga)盆地河流中野生卡特拉(鱾)种群的年龄结构和重要生长参数,对该鱼的年龄和生长进行了研究.鳞片取自商业捕捞和实验室饲养的样品.根据研究分析,该鱼最大年龄可达8龄;巴吉拉蒂河(Bhagirathi R.)的种群平均体长为521.51 mm,退算体长为288.9-1132.3 mm;旁遮普邦(Punjab)Satluj河种群平均体长为641.6 mm,退算体长为335.4-1096.08 mm.2龄时,种群线性生长率(Cl)和体重增加率(Cw)表现出迅速下降的趋势.其它生长参数值(Clt)也呈现快速下降.退算体长差异(ANOVA)分析显示,生活在赣达盆地不同流域中的种群,1 -4 龄组的长度差异较明显(P<0.05),高龄组(5 -8 )差异不显著.根据本项研究结果,提出了对印度北部赣达盆地相关河流中生活的野生卡特拉(鱾)种群资源持续利用的对策. 相似文献