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排序方式: 共有4532条查询结果,搜索用时 15 毫秒
1.
Yasmin Husaini Glen P. Lockwood Trung V. Nguyen Vicky Wang-Wei Tsai Mohammad G. Mohammad Pamela J. Russell David A. Brown Samuel N. Breit 《PloS one》2015,10(2)
The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa). Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMPMIC-/-). On average TRAMPMIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMPMIC+/+). Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMPMIC+/+ and TRAMPMIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMPfmsmic-1) had metastases than TRAMPMIC+/+ mice (p<0.0001). We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread. 相似文献
2.
Nicking by transesterification: the reaction catalysed by a relaxase 总被引:17,自引:5,他引:12
DNA relaxases play an essential role in the initiation and termination of conjugative DNA transfer. Purification and characterization of relaxases from several plasmids has revealed the reaction mechanism: relaxases nick duplex DNA in a site- and strand-specific manner by catalysing a transesterification. The product of the reaction is a nicked double-stranded DNA molecule with a sequestered 3'-OH and the relaxase covalently bound to the 5' end of the cleaved strand via a phosphotyrosyl linkage. The relaxase-catalysed transesterification is isoenergetic and reversible; a second transesterification ligates the nicked DNA. However, the covalent nucleoprotein complex is relatively long-lived, a property that is likely to be essential for its role as an intermediate in the process of conjugative DNA transfer. Subsequent unwinding of the nicked DNA intermediate is required to produce the single strand of DNA transferred to the recipient cell. This reaction is catalysed by a DNA helicase, an activity intrinsic to the relaxase protein in some, but not all, plasmid systems. The first relaxase-catalysed transesterification is essential for initiation of conjugative strand transfer, whereas the second is presumably required for termination of the process. The relaxase, in conjunction with several auxiliary proteins, forms the relaxation complex or relaxosome first described nearly 30 years ago as being associated with conjugative and mobilizable plasmids. 相似文献
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Ana Maria Fernandez-Pujals Mark James Adams Pippa Thomson Andrew G. McKechanie Douglas H. R. Blackwood Blair H. Smith Anna F. Dominiczak Andrew D. Morris Keith Matthews Archie Campbell Pamela Linksted Chris S. Haley Ian J. Deary David J. Porteous Donald J. MacIntyre Andrew M. McIntosh 《PloS one》2015,10(11)
The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD. 相似文献
5.
Elizabeth A. Kingsley Teresa E. Carter Kevin D. Barrow Pamela J. Russell 《Cancer immunology, immunotherapy : CII》1996,41(6):348-354
A monoclonal antibody, BLCA-8, was raised against the human bladder cancer cell line, UCRU-BL-17CL. By flow cytometry and immunoperoxidase staining, this antibody was found to possess high specificity for bladder tumours, some reactivity with fetal tissues, and no reactivity with normal bladder, or any normal or malignant tissue. This high specificity and the stability of the antigen to the urinary environment suggest that BLCA-8 may have potential for use as an anti-bladder-cancer therapeutic agent. By thin-layer chromatography and autoradiography, BLCA-8 was found to bind four components within the neutral lipid fraction of a bladder cancer cell line, UCRU-BL-17/23. These components hadR
F values of 0.22, 0.16/0.15 (doublet), 0.12 and 0.08, and migrated below globoside, indicating the presence of more than four sugars. By enzyme-linked immunosorbant assay and thin-layer chromatography it was found that the binding of BLCA-8 to the lipid extract was increased by both mild alkaline hydrolysis and enzymatic treatments, indicating that adjacent phospholipids and glycolipids interfere with the accessibility of the antibody-binding site. Full biochemical characterisation of the BLCA-8 antigen is currently underway. 相似文献
6.
M S Wehnert R S Matson J B Rampal P J Coassin C T Caskey 《Nucleic acids research》1994,22(9):1701-1704
Oligonucleotides representing 60 trinucleotide (21mers) and four dinucleotide (20mers) tandem repeats were directly synthesized and arrayed onto an aminated polypropylene substrate. DNA samples of different complexities (a CAG-containing 21mer oligonucleotide, PCR fragments of 200 to 3,000 bp, and cosmids with 31 to 35 kb inserts) were radiolabelled and hybridized to the oligonucleotide array at various temperatures. When compared to sequence data available from the test DNAs, the reverse blot system specifically identified various tri- and dinucleotide short tandem repeats (STRs) in every case. Moreover, there was no random or cross hybridization to nonspecific sequences. It was possible to detect as few as three repeated units in a particular location, as shown for (CCT)n, (GCC)n and (CAC)n triplets in cosmid DNA. Varying the hybridization stringency can enhance the detection of STRs. This single-step reverse blot system therefore allows the rapid, specific and sensitive identification of various STRs in DNA sources of different complexity. 相似文献
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8.
Callie H. Crawford Zachary S. Randall Pamela B. Hart Lawrence M. Page Prosanta Chakrabarty Apinun Suvarnaraksha Brooke E. Flammang 《Journal of morphology》2020,281(10):1280-1295
The rheophilic hillstream loaches (Balitoridae) of South and Southeast Asia possess a range of pelvic girdle morphologies, which may be attributed to adaptations for locomotion against rapidly flowing water. Specifically, the connectivity of the pelvic plate (basipterygium) to the vertebral column via a sacral rib, and the relative size and shape of the sacral rib, fall within a spectrum of three discrete morphotypes: long, narrow rib that meets the basipterygium; thicker, slightly curved rib meeting the basipterygium; and robust crested rib interlocking with the basipterygium. Species in this third category with more robust sacral rib connections between the basipterygium and vertebral column are capable of walking out of water with a tetrapod-like lateral-sequence, diagonal-couplet gait. This behavior has not been observed in species lacking direct skeletal connection between the vertebrae and the pelvis. The phylogenetic positions of the morphotypes were visualized by matching the morphological features onto a novel hypothesis of relationships for the family Balitoridae. The morphotypes determined through skeletal morphology were correlated with patterns observed in the pelvic muscle morphology of these fishes. Transitions towards increasingly robust pelvic girdle attachment were coincident with a more anterior origin on the basipterygium and more lateral insertion of the muscles on the fin rays, along with a reduction of the superficial abductors and adductors with more posterior insertions. These modifications are expected to provide a mechanical advantage for generating force against the ground. Inclusion of the enigmatic cave-adapted balitorid Cryptotora thamicola into the most data-rich balitorid phylogeny reveals its closest relatives, providing insight into the origin of the skeletal connection between the axial skeleton and basipterygium. 相似文献
9.
Anke Bill Michelle Lynn Hall Jason Borawski Catherine Hodgson Jeremy Jenkins Philippe Piechon Oana Popa Christopher Rothwell Pamela Tranter Scott Tria Trixie Wagner Lewis Whitehead L. Alex Gaither 《The Journal of biological chemistry》2014,289(16):11029-11041
ANO1, a calcium-activated chloride channel, is highly expressed and amplified in human cancers and is a critical survival factor in these cancers. The ANO1 inhibitor CaCCinh-A01 decreases proliferation of ANO1-amplified cell lines; however, the mechanism of action remains elusive. We explored the mechanism behind the inhibitory effect of CaCCinh-A01 on cell proliferation using a combined experimental and in silico approach. We show that inhibition of ANO1 function is not sufficient to diminish proliferation of ANO1-dependent cancer cells. We report that CaCCinh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulum-associated, proteasomal turnover of ANO1. Washout of CaCCinh-A01 rescued ANO1 protein levels and resumed cell proliferation. Proliferation of newly derived CaCCinh-A01-resistant cell pools was not affected by CaCCinh-A01 as compared with the parental cells. Consistently, CaCCinh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCCinh-A01, indicating that CaCCinh-A01 inhibits cell proliferation by reducing ANO1 protein levels. Furthermore, we employed in silico methods to elucidate novel biological functions of ANO1 inhibitors. Specifically, we derived a pharmacophore model to describe inhibitors capable of promoting ANO1 degradation and report new inhibitors of ANO1-dependent cell proliferation. In summary, our data demonstrate that inhibition of the channel activity of ANO1 is not sufficient to inhibit ANO1-dependent cell proliferation, indicating that the role of ANO1 in cancer only partially depends on its function as a channel. Our results provide an impetus for gaining a deeper understanding of ANO1 modulation in cells and introduce a new targeting approach for antitumor therapy in ANO1-amplified cancers. 相似文献
10.
Aditya S. Khanna Sarah T. Roberts Susan Cassels Roger Ying Grace John-Stewart Steven M. Goodreau Jared M. Baeten Pamela M. Murnane Connie Celum Ruanne V. Barnabas 《PloS one》2015,10(8)