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101.
Inhibitory effects of food additives on toxicity induced by aflatoxin B1 was conducted in 3-day-old ducklings. Aflatoxin B1 at a dose of 5 μg/day per animal for 14 days induced severe liver damage which included necrosis, fatty changes, and biliary hyperplasia. These changes were found to be inhibited by the daily administration of turmeric (50mg), curcumin (10 mg), and ellagic acid (10 mg) in the diet. Addition of BHA-butylated hydroxy anisole (10 mg), BHT-butylated hydroxy toluene (10 mg), garlic (500 mg), and asafoetida (50 mg) inhibited necrosis and degeneration of the tissue, while biliary hyperplasia persisted. Biochemical and haematological parameters were not significantly altered under the conditions studied. 相似文献
102.
Wandong Zhang Katerina V. Savelieva David T. Tran Vladimir M. Pogorelov Emily B. Cullinan Kevin B. Baker Kenneth A. Platt Sean Hu Indrani Rajan Nianhua Xu Thomas H. Lanthorn 《PloS one》2012,7(9)
Receptor tyrosine phosphatase gamma (PTPRG, or RPTPγ) is a mammalian receptor-like tyrosine phosphatase which is highly expressed in the nervous system as well as other tissues. Its function and biochemical characteristics remain largely unknown. We created a knockdown (KD) line of this gene in mouse by retroviral insertion that led to 98–99% reduction of RPTPγ gene expression. The knockdown mice displayed antidepressive-like behaviors in the tail-suspension test, confirming observations by Lamprianou et al. 2006. We investigated this phenotype in detail using multiple behavioral assays. To see if the antidepressive-like phenotype was due to the loss of phosphatase activity, we made a knock-in (KI) mouse in which a mutant, RPTPγ C1060S, replaced the wild type. We showed that human wild type RPTPγ protein, expressed and purified, demonstrated tyrosine phosphatase activity, and that the RPTPγ C1060S mutant was completely inactive. Phenotypic analysis showed that the KI mice also displayed some antidepressive-like phenotype. These results lead to a hypothesis that an RPTPγ inhibitor could be a potential treatment for human depressive disorders. In an effort to identify a natural substrate of RPTPγ for use in an assay for identifying inhibitors, “substrate trapping” mutants (C1060S, or D1028A) were studied in binding assays. Expressed in HEK293 cells, these mutant RPTPγs retained a phosphorylated tyrosine residue, whereas similarly expressed wild type RPTPγ did not. This suggested that wild type RPTPγ might auto-dephosphorylate which was confirmed by an in vitro dephosphorylation experiment. Using truncation and mutagenesis studies, we mapped the auto-dephosphorylation to the Y1307 residue in the D2 domain. This novel discovery provides a potential natural substrate peptide for drug screening assays, and also reveals a potential functional regulatory site for RPTPγ. Additional investigation of RPTPγ activity and regulation may lead to a better understanding of the biochemical underpinnings of human depression. 相似文献
103.
J A Bluestone T A Potter S Chatterjee-Hasrouni T V Rajan 《Journal of immunology (Baltimore, Md. : 1950)》1984,133(3):1168-1173
Reciprocal Ld structural mutants have been isolated from a somatic cell line. Testing of allogeneic CTL clones on these mutants suggests that the majority of CTL clones recognize determinants different from those that elicit antibody production. Of 36 CTL clones tested, only three clones appeared to recognize a determinant that was related to the negatively selected serologic determinant. However, mAb blocking studies suggest that inhibition of CTL activity by anti-H-2 mAb does not necessarily reflect the fine specificity of the CTL activity. 相似文献
104.
Spontaneous deletion at the B2m locus: evidence for site-specific genetic rearrangement 总被引:2,自引:0,他引:2
T A Potter W Frankel R A Zeff T V Rajan 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(4):1270-1274
We have isolated 20 independent spontaneous mutants in the B2mb allele from a B2ma/b heterozygous murine cell line by immunoselection in vitro with a monoclonal antibody directed against the product of the B2mb allele. One class of mutants has undergone a deletion in the 5' end of the B2mb gene. The deletions appear to be identical in all of the independent clones, and extend an unknown distance upstream of the B2m gene from a region in the first intron. Southern blot analysis with the use of oligonucleotides to the wild type gene sequence mapped the breakpoint to within 39 base pairs. The high frequency of independent spontaneous mutants showing indistinguishable deletions suggests that the first intron of the B2m gene contains sequences that are highly susceptible to site-specific recombinations. 相似文献
105.
As defined by IEEE 802.15.6 standard, channel sharing is a potential method to coordinate inter-network interference among Medical Body Area Networks (MBANs) that are close to one another. However, channel sharing opens up new vulnerabilities as selfish MBANs may manipulate their online channel requests to gain unfair advantage over others. In this paper, we address this issue by proposing a truthful online channel sharing algorithm and a companion protocol that allocates channel efficiently and truthfully by punishing MBANs for misreporting their channel request parameters such as time, duration and bid for the channel. We first present an online channel sharing scheme for unit-length channel requests and prove that it is truthful. We then generalize our model to settings with variable-length channel requests, where we propose a critical value based channel pricing and preemption scheme. A bid adjustment procedure prevents unbeneficial preemption by artificially raising the ongoing winner’s bid controlled by a penalty factor
λ. Our scheme can efficiently detect selfish behaviors by monitoring a trust parameter α of each MBAN and punish MBANs from cheating by suspending their requests. Our extensive simulation results show our scheme can achieve a total profit that is more than 85% of the offline optimum method in the typical MBAN settings. 相似文献
106.
107.
Rajan Kumar Choudhary Vikrant Quadir M. Siddiqui Pankaj S. Thapa Sweta Raikundalia Nikhil Gadewal 《Journal of biomolecular structure & dynamics》2016,34(7):1533-1544
BARD1–BRCA1 complex plays an important role in DNA damage repair, apoptosis, chromatin remodeling, and other important processes required for cell survival. BRCA1 and BARD1 heterodimer possess E3 ligase activity and is involved in genome maintenance, by functioning in surveillance for DNA damage, thereby regulating multiple pathways including tumor suppression. BRCT domains are evolutionary conserved domains present in different proteins such as BRCA1, BARD1, XRCC, and MDC1 regulating damage response and cell-cycle control through protein–protein interactions. Nonetheless, the role of BARD1BRCT in the recruitment of DNA repair mechanism and structural integrity with BRCA1 complex is still implicit. To explicate the role of BARD1BRCT in the DNA repair mechanism, in silico, in vitro, and biophysical approach were applied to characterize BARD1 BRCT wild-type and Arg658Cys and Ile738Val mutants. However, no drastic secondary and tertiary structural changes in the mutant proteins were observed. Thermal and chemical denaturation studies revealed that mutants Arg658Cys and Ile738Val have a decrease in Tm and ?G than the wild type. In silico studies of BARD1 BRCT (568-777) and mutant protein indicate loss in structural compactness on the Ile738Val mutant. Comparative studies of wild-type and mutants will thus be helpful in understanding the basic role of BARD1BRCT in DNA damage repair. 相似文献
108.
Soluble Collagen VI Induces Tyrosine Phosphorylation of Paxillin and Focal Adhesion Kinase and Activates the MAP Kinase Erk2 in Fibroblasts 总被引:2,自引:0,他引:2
Martin Rühl Manfred Johannsen Jane Atkinson Dirk Manski Ergün Sahin Rajan Somasundaram Ernst Otto Riecken Detlef Schuppan 《Experimental cell research》1999,250(2):548-557
Signals from the extracellular matrix can modulate cellular differentiation and gene expression. We have shown previously that in contrast to other extracellular matrix molecules pepsin-solubilized collagen VI (CVI) can stimulate DNA synthesis of various mesenchymal cell types, apparently independent of integrin-mediated signal transduction. In order to further elucidate collagen VI-induced signaling events, we exposed mouse 3T3 fibroblasts and human HT1080 fibrosarcoma cells to soluble CVI. CVI induced tyrosine phosphorylation of proteins that associate with focal adhesions, such as paxillin, focal adhesion kinase (FAK), and p130CAS. Furthermore, it activated the mitogen-activated protein kinase, erk2. Kinetic analysis showed that these phosphorylations were transient, reaching a maximum after 5 min for transformed HT1080 cells and 30 min for 3T3 fibroblasts. These effects were partly inhibited by a beta1-integrin function blocking antibody and by single chains of CVI. Our results indicate that soluble fragments of native collagen VI, a ubiquitous component of the interstitial extracellular matrix, can mediate stimulation of DNA synthesis via tyrosine phosphorylation of paxillin, FAK, p130CAS, and erk2 in the absence of classical growth factors. Thus, CVI may serve as a matrix-derived sensor that allows for rapid reconstitution of a tissue defect by activating nearby mesenchymal cells. 相似文献
109.
Pradeep Kumar Maharana Triranjita Srivastava Rajan Jha 《Plasmonics (Norwell, Mass.)》2014,9(5):1113-1120
We demonstrate the numerical analysis of surface plasmon resonance biosensor based on graphene on aluminum and silicon. Employing matrix method, it is found that the proposed sensor exhibits high imaging sensitivity ~400 RIU?1 to 550 RIU?1 in a large dynamic range from visible to near IR region. It is observed that the application of monolayer or bilayer graphene over aluminum not only protects it from oxidation but also enhances the adsorption of biomolecules, which results in the detection of large refractive indices ranging from aqueous solution to biomolecules (refractive index 1.330 to 1.480) with overall high performance in terms of imaging sensitivity and detection accuracy. 相似文献
110.
The HER/ErbB family of receptor tyrosine kinases drives critical responses in normal physiology and cancer, and the expression levels of the various HER receptors are critical determinants of clinical outcomes. HER activation is driven by the formation of various dimer complexes between members of this receptor family. The HER dimer types can have differential effects on downstream signaling and phenotypic outcomes. We constructed an integrated mathematical model of HER activation, and trafficking to quantitatively link receptor expression levels to dimerization and activation. We parameterized the model with a comprehensive set of HER phosphorylation and abundance data collected in a panel of human mammary epithelial cells expressing varying levels of EGFR/HER1, HER2 and HER3. Although parameter estimation yielded multiple solutions, predictions for dimer phosphorylation were in agreement with each other. We validated the model using experiments where pertuzumab was used to block HER2 dimerization. We used the model to predict HER dimerization and activation patterns in a panel of human mammary epithelial cells lines with known HER expression levels in response to stimulations with ligands EGF and HRG. Simulations over the range of expression levels seen in various cell lines indicate that: i) EGFR phosphorylation is driven by HER1-HER1 and HER1-HER2 dimers, and not HER1-HER3 dimers, ii) HER1-HER2 and HER2-HER3 dimers both contribute significantly to HER2 activation with the EGFR expression level determining the relative importance of these species, and iii) the HER2-HER3 dimer is largely responsible for HER3 activation. The model can be used to predict phosphorylated dimer levels for any given HER expression profile. This information in turn can be used to quantify the potencies of the various HER dimers, and can potentially inform personalized therapeutic approaches. 相似文献