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31.

Background  

The present paper describes a topological model of biofeedback. This model incorporates input from a sensory organ and a transduction phase mediated through catecholamine production in the feedback path. The transduction phase comprises both conservative and dissipative systems, from which the appropriate output is combined in a closed loop.  相似文献   
32.
Mammalian bombesin (BN) receptors are among those most frequently overexpressed by a number of common tumors including prostate, breast, lung, and colon cancers. The aim of this study was to develop a camptothecin-bombesin (CPT-BN) conjugate that interacts with all classes of BN receptors and possibly functions as a prodrug via a labile linker with site-specific cytotoxicity for cancer cells bearing these receptors. CPT was coupled to analogs of [D-Tyr6,beta-Ala11,Phe13,Nle14]BN-(6-14) (BA0) using carbamate linkers (L1 and L2) with built-in nucleophile-assisted releasing groups for intracellular cleavage of free cytotoxic agents. One conjugate, CPT-L2-BA3, bound to all three BN receptor classes with high affinity and functioned as a full agonist at each. 125I-CPT-L2-BA3 was rapidly internalized by cells expressing each BN receptor class and, using fluorescent imaging, was found to co-localize with BN receptors initially and later to be internalized in cytoplasmic compartments. HPLC analysis of internalized ligand showed that 40% was intact, 25% was metabolized by releasing free CPT, and 35% was metabolized to other breakdown products. CPT-L2-BA3 inhibited the growth of NCI-H1299 non-small cell lung cancer cells in 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyl-2H-tetrazolium bromide (MTT) and clonal growth assays. CPT-L2-BA3 was cytotoxic in an MTT assay for cells transfected with each class of BN receptor; however, it had significantly less effect in cells lacking BN receptors. These results indicate that CTP-L2-BA3 is a potent agonist that is cytotoxic for cells overexpressing any of the three BN receptor classes and functions as a prodrug for receptor-mediated cytoxicity. It therefore should be a useful prototype to explore the effectiveness of tumor-specific cytotoxicity delivery using a receptor-mediated mechanism.  相似文献   
33.
[VIVO(acac)2] reacts with the methanol solution of tridentate ONO donor hydrazone ligands (H2L1-4, general abbreviation H2L; are derived from the condensation of benzoyl hydrazine with 2-hydroxyacetophenone and its 5-substituted derivatives) in presence of neutral monodentate alkyl amine bases having stronger basicity than pyridine e.g., ethylamine, diethylamine, triethylamine and piperidine (general abbreviation B) to produce BH+[VO2L] (1-16) complexes. Five of these sixteen complexes are structurally characterized revealing that the vanadium is present in the anionic part of the molecule, [VO2L] in a distorted square pyramidal environment. The complexes 5, 6, 15 and 16 containing two H-atoms associated with the amine-N atom in their cationic part (e.g., diethylammonium and piperidinium ion) are involved in H-bonding with a neighboring molecule resulting in the formation of centrosymmetric dimers while the complex 12 (containing only one hydrogen atom in the cationic part) exhibits normal H-bonding. The nature of the H-bonds in each of the four centrosymmetric dimeric complexes is different. These complexes have potential catalytic activity in the aerial oxidation of l-ascorbic acid and are converted into the [VO(L)(hq)] complexes containing VO3+ motif on reaction with equimolar amount of 8-hydroxyquinoline (Hhq) in methanol.  相似文献   
34.
Tight junctions (TJs) in endothelial cells act as cell-cell adhesion structures, governing paracellular permeability (PCP). Disruption can lead to leaky vascular bed and potentially to oedema and swelling of tissues, the aetiology of mastalgia. These changes may also cause vascular spread of cancer cells. This study aimed to determine whether the function of TJs in endothelial cells can be strengthened by gamma linolenic acid (GLA), selenium (Se) and iodine (I) in the presence of 17beta-estradiol (17beta-estradiol), which causes leakage of endothelial cells by disruption of TJs in endothelium. GLA, I, and Se individually increased transendothelial resistance. The combination of all three agents also had a significant effect on TER. Addition of GLA/Se/I reduced PCP of the endothelial cells. Treatment with GLA/Se/I reversed the effect of 17beta-estradiol in reducing TER and increasing PCP. Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h there was increasing relocation to endothelial cell-cell junctions of the TJ proteins Claudin-5, Occludin, and ZO-1. Interestingly, this relocation was particularly evident with treatments containing I when probing with Claudin-5 and those containing Se for Occludin. There was a small increase in overall protein levels when examined by Western blotting after treatment with GLA/Se/I when probed with Claudin-5 and Occludin. We report that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells, by way of regulating the distribution of Claudin-5, Occludin, and ZO-1. Interestingly, this combination was also able to completely reverse the effect of 17beta-estradiol in these cells.  相似文献   
35.
Many efforts based on complete mitochondrial DNA (mtDNA) genomeshave been made to depict the global mtDNA landscape, but thephylogeny of Indian macrohaplogroup M has not yet been resolvedin detail. To fill this lacuna, we took the same strategy asin our recent analysis of Indian mtDNA macrohaplogroup N andselected 56 mtDNAs from over 1,200 samples across India forcomplete sequencing, with the intention to cover all Indianautochthonous M lineages. As a result, the phylogenetic statusof previously identified haplogroups based on control-regionand/or partial coding-region information, such as M2, M3, M4,M5, M6, M30, and M33, was solidified or redefined here. Moreover,seven novel basal M haplogroups (viz., M34–M40) were identified,and yet another five singular branches of the M phylogeny werediscovered in the present study. The comparison of matrilinealcomponents among India, East Asia, Southeast Asia, and Oceaniaat the deepest level yielded a star-like and nonoverlappingpattern, reflecting a rapid mode of modern human dispersal alongthe Asian coast after the initial "out-of-Africa" event.  相似文献   
36.
We describe the morphology of the attachment organ (AO) of the teleost, Garra gotyla gotyla (Cyprinidae). It is located ventrally around the mouth opening and used by the species for attachment to submerged rocks in sub-Himalayan streams and rivers where it lives. The AO consists of three crescentic parts and a central callus part. Scanning electron microscopy (SEM) shows the former to possess numerous tubercles, each of which bears about 23–27 curved spines. Light microscopy shows the epidermis of the tuberculated parts to possess one type of cell arranged into 7–8 rows. Transmission electron microscopy (TEM) reveals these cells to contain abundant tonofilaments (hence called the filament cells). The epidermis of the callus part possesses the filament cells and additionally mucous cells, which are absent in the tuberculated parts. The superficial epidermis is apparently keratinized (thickness: 5–8 μm), and a part of the cells of the outer row is modified into spines. These cells show a thick plasma membrane envelope and possess mucous granules (diameter: 0.1–0.3 μm) and bundles of tonofilaments. The cells of the inner two to four rows possess similar organelles and additionally, prominent Golgi bodies and rough endoplasmic reticulum. Immunohistochemically, the cells of the outer row and the spines stain positively for cytokeratin. The cells of the innermost rows (five to eight) possess few tonofilaments and no mucous granules. It is evident that the filament cells of the mid- to upper epidermis are specialized for the production of mucous granules and tonofilaments, which is unique for the teleost epidermis concerned. It appears that the tuberculated parts with spines assist in anchorage and interlocking with the substratum, while the central callus part probably utilizes both suction and frictional mechanisms, and mucous secretion protects the spines from damage during anchorage and abrasion.  相似文献   
37.
38.

Background

The objective of this study was to establish the buffalo mammary epithelial cell line (BuMEC) and characterize its mammary specific functions.

Methodology

Buffalo mammary tissue collected from the slaughter house was processed enzymatically to obtain a heterogenous population of cells containing both epithelial and fibroblasts cells. Epithelial cells were purified by selective trypsinization and were grown in a plastic substratum. The purified mammary epithelial cells (MECs) after several passages were characterized for mammary specific functions by immunocytochemistry, RT-PCR and western blot.

Principal Findings

The established buffalo mammary epithelial cell line (BuMEC) exhibited epithelial cell characteristics by immunostaining positively with cytokeratin 18 and negatively with vimentin. The BuMEC maintained the characteristics of its functional differentiation by expression of β-casein, κ-casein, butyrophilin and lactoferrin. BuMEC had normal growth properties and maintained diploid chromosome number (2n = 50) before and after cryopreservation. A spontaneously immortalized buffalo mammary epithelial cell line was established after 20 passages and was continuously subcultured for more than 60 passages without senescence.

Conclusions

We have established a buffalo mammary epithelial cell line that can be used as a model system for studying mammary gland functions.  相似文献   
39.
The link between loss or defect in functional BRCA1 and predisposition for development of ovarian and breast cancer is well established. Germ-line mutations in BRCA1 are responsible for both hereditary breast and ovarian cancer, which is around 5–10% for all breast and 10–15% of all ovarian cancer cases. However, majority of cases of ovarian cancer are sporadic in nature. The inactivation of cellular BRCA1 due to mutations or loss of heterozygosity is one of the most commonly observed events in such cases. Complement-resistant retroviral BRCA1 vector, MFG-BRCA1, is the only approved gene therapy for ovarian cancer patients by the Federal and Drug Administration. Given the limited available information, there is a need to evaluate the effects of BRCA1 on the global gene expression pattern for better understanding the etiology of the disease. Here, we use Ingenuity Pathway Knowledge Base to examine the differential pattern of global gene expression due to stable expression of BRCA1 in the ovarian cancer cell line, SKOV3. The functional analysis detected at least five major pathways that were significantly (p < 0.05) altered. These include: cell to cell signaling and interaction, cellular function and maintenance, cellular growth and proliferation, cell cycle and DNA replication, and recombination repair. In addition, we were able to detect several biologically relevant genes that are central for various signaling networks involved in cellular homeostasis; TGF-β1, TP53, c-MYC, NF-κB and TNF-α. This report provides a comprehensive rationale for tumor suppressor function(s) of BRCA1 in ovarian carcinogenesis.  相似文献   
40.
Human NEIL2, one of five oxidized base-specific DNA glycosylases, is unique in preferentially repairing oxidative damage in transcribed genes. Here we show that depletion of NEIL2 causes a 6-7-fold increase in spontaneous mutation frequency in the HPRT gene of the V79 Chinese hamster lung cell line. This prompted us to screen for NEIL2 variants in lung cancer patients' genomic DNA. We identified several polymorphic variants, among which R103Q and R257L were frequently observed in lung cancer patients. We then characterized these variants biochemically, and observed a modest decrease in DNA glycosylase activity relative to the wild type (WT) only with the R257L mutant protein. However, in reconstituted repair assays containing WT NEIL2 or its R257L and R103Q variants together with other DNA base excision repair (BER) proteins (PNKP, Polβ, Lig IIIα and XRCC1) or using NEIL2-FLAG immunocomplexes, an ~5-fold decrease in repair was observed with the R257L variant compared to WT or R103Q NEIL2, apparently due to the R257L mutant's lower affinity for other repair proteins, particularly Polβ. Notably, increased endogenous DNA damage was observed in NEIL2 variant (R257L)-expressing cells relative to WT cells. Taken together, our results suggest that the decreased DNA repair capacity of the R257L variant can induce mutations that lead to lung cancer development.  相似文献   
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