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51.
Although the amino acid glutamate is used as an intercellular signaling molecule for normal bone homeostasis, little is known regarding its possible role in the metabolic disruption characteristic of bone metastasis. We have previously shown in vitro that cancer cell lines relevant to bone metastasis release glutamate into the extracellular environment. This study demonstrates the expression of multiple glutamate transporters in cancer cell lines of non-central nervous system origin. Furthermore, we identify the molecular mechanism responsible for glutamate export and show that this system can be inhibited pharmacologically. By highlighting that glutamate secretion is a common biological feature of cancer cells, this study suggests that tumor-derived glutamate could interfere with glutamate-dependent intercellular signaling in normal bone. Pharmacological interference with cancer cell glutamate release may be a viable option for limiting host bone response to invading tumor cells in bone metastasis. 相似文献
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OPC (oligodendrocyte progenitor cell) death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H–I (hypoxia–ischemia) in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL–Bax association in white matter following H–I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax–cofilin association was disrupted during glutamate-induced OPC apoptosis. 相似文献
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Border cells in the Drosophila ovary originate within an epithelium, detach from it, invade neighboring nurse cells, and migrate as a coherent cluster. This migration has served as a useful genetic model for understanding epithelial cell motility. The prevailing model of growth factor-mediated chemotaxis in general, and of border cells in particular, posits that receptor activation promotes cellular protrusion at the leading edge. Here we report the time-lapse video imaging of border cell migration, allowing us to test this model. Reducing the activities of the guidance receptors EGFR and PVR did not result in the expected inhibition of protrusion, but instead resulted in protrusion in all directions. In contrast, reduction in Notch activity resulted in failure of the cells to detach from the epithelium without affecting direction sensing. These observations provide new insight into the cellular dynamics and molecular mechanisms of cell migration in vivo. 相似文献
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Mohit Midha Raja Polavarapu Potshangbam Angamba Meetei Hari Krishnan Krishnaveni Mohareer Vaibhav Vindal 《Bioinformation》2012,8(15):738-739
Identification of ortholog is one of the important tasks to understand a novel genome. It helps to assign functional annotations,
from one organism to another organism. To identify the putative ortholog, Reciprocal Best BLAST hit (RBBH) method is known to
be an efficient approach. OrFin makes use of the same approach to identify pair of orthologous proteins for a given set of sequences
of two species. It is a user-friendly web tool which works with user defined parameters to search RBBHs. Results are produced in
both html and text format.
Availability
This web tool is freely available at http://bifl.uohyd.ac.in/orfin 相似文献57.
Wang J Leone P Wu G Francis JS Li H Jain MR Serikawa T Ledeen RW 《Neurochemical research》2009,34(1):138-148
The high concentration of N-acetylaspartate (NAA) in neurons of the central nervous system and its growing clinical use as an indicator of neuronal viability
has intensified interest in the biological function of this amino acid derivative. The biomedical relevance of such inquiries
is highlighted by the myelin-associated pathology of Canavan disease, an inherited childhood disorder resulting from mutation
of aspartoacylase (ASPA), the NAA-hydrolyzing enzyme. This enzyme is known to be localized in oligodendrocytes with bimodal
distribution in cytosol and the myelin sheath, and to produce acetyl groups utilized in myelin lipid synthesis. Loss of this
acetyl source in Canavan disease and rodent models such as the tremor rat are thought to account for the observed myelin deficit.
This study was undertaken to further define and quantify the specific lipid abnormalities that occur as a result of ASPA deficit
in the tremor rat. Employing mass spectrometry together with high performance thin-layer chromatography, we found that myelin
from 28-day-old animals showed major reduction in cerebrosides (CB) and sulfatides (Sulf) with unsubstituted fatty acids,
and equal if not greater changes in myelin from 7-month-old tremors. Cerebrosides with 2-hydroxyfatty acids showed little
if any change at either age; Sulf with 2-hydroxyfatty acids showed no significant change at 28 days, but surprisingly a major
increase at 7 months. Two species of phosphatidylcholine, 32:0 and 34:1, also showed significant increase, but only at 28 days.
One form of phosphatidylethanolamine, PE36:1, was reduced a modest amount at both ages, whereas the plasmalogen form did not
change. The dysmyelination that results from inactivation of ASPA is thus characterized by selective decreases as well as
some increases in specific lipids.
Special issue article in honor of Dr. George DeVries.
Fatty acid designations (e.g. 18:1) indicate carbon number and number of double bonds. 相似文献
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Ashish Fauzdar Mohit Chowdhry R. N. Makroo Manoj Mishra Priyanka Srivastava Richa Tyagi Preeti Bhadauria Anita Kaul 《Indian journal of human genetics》2013,19(1):32-42
BACKGROUND AND OBJECTIVE:
Women with high-risk pregnancies are offered prenatal diagnosis through amniocentesis for cytogenetic analysis of fetal cells. The aim of this study was to evaluate the effectiveness of the rapid fluorescence in situ hybridization (FISH) technique for detecting numerical aberrations of chromosomes 13, 21, 18, X and Y in high-risk pregnancies in an Indian scenario.MATERIALS AND METHODS:
A total of 163 samples were received for a FISH and/or a full karyotype for prenatal diagnosis from high-risk pregnancies. In 116 samples both conventional culture techniques for getting karyotype through G-banding techniques were applied in conjunction to FISH test using the AneuVysion kit (Abbott Molecular, Inc.), following standard recommended protocol to compare the both the techniques in our setup.RESULTS:
Out of 116 patients, we got 96 normal for the five major chromosome abnormality and seven patients were found to be abnormal (04 trisomy 21, 02 monosomy X, and 01 trisomy 13) and all the FISH results correlated with conventional cytogenetics. To summarize the results of total 163 patients for the major chromosomal abnormalities analyzed by both/or cytogenetics and FISH there were 140 (86%) normal, 9 (6%) cases were abnormal and another 4 (2.5%) cases were suspicious mosaic and 10 (6%) cases of culture failure. The diagnostic detection rate with FISH in 116 patients was 97.5%. There were no false-positive and false-negative autosomal or sex chromosomal results, within our established criteria for reporting FISH signals.CONCLUSION:
Rapid FISH is a reliable and prompt method for detecting numerical chromosomal aberrations and has now been implemented as a routine diagnostic procedure for detection of fetal aneuploidy in India. 相似文献60.
Viraj Bhat Manish Parashar Hua Liu Nagarajan Kandasamy Mohit Khandekar Scott Klasky Sherif Abdelwahed 《Cluster computing》2007,10(4):365-383
Efficient and robust data streaming services are a critical requirement of emerging Grid applications, which are based on
seamless interactions and coupling between geographically distributed application components. Furthermore the dynamism of
Grid environments and applications requires that these services be able to continually manage and optimize their operation
based on system state and application requirements. This paper presents a design and implementation of such a self-managing
data-streaming service based on online control strategies. A Grid-based fusion workflow scenario is used to evaluate the service
and demonstrate its feasibility and performance.
相似文献
Sherif AbdelwahedEmail: |