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11.
M. Moorghen P. Ince Karen J. Finney A. J. Watson A. L. Harris 《In vitro cellular & developmental biology. Animal》1991,27(11):873-877
Summary The in-vitro effects of hydroxyurea 5-FU and 5-FUdR have been extensively studied in experimental systems employing cell-line
techniques. In this study we investigated the effects of these drugs on the levels of incorporation of labeled nucleosides
into DNA in explants of intact rat colonic mucosa maintained in organ culture. The effects of the nucleoside transport inhibitors
nitrobenzylthioinosine (NBMPR) and dipyridamole—which are modulators of antimetabolite cytotoxicity—on the incorporation of
tritiated thymidine [(3H]TdR) into DNA were also studied. The incorporation of tritiated TdR into DNA was reduced by hydroxyurea but was not altered
by either 5-FU or 5-FUdR. The levels of tritiated deoxyuridine were reduced by 5-FU and 5-FUdR in separate experiments; this
is in keeping with thymidylate synthase inhibition. NBMPR and dipyridamole also reduced 3H-TdR incorporation into DNA. These
results can be explained in terms of the known mechanisms of action of these drugs. This experimental model is therefore useful
in assessing the effects of antimetabolites and nucleoside transport inhibitors in intact colonic mucosa. 相似文献
12.
13.
Rosemary Braun Richard Finney Chunhua Yan Qing-Rong Chen Ying Hu Michael Edmonson Daoud Meerzaman Kenneth Buetow 《PloS one》2013,8(3)
Background
Ovarian cancer remains a significant public health burden, with the highest mortality rate of all the gynecological cancers. This is attributable to the late stage at which the majority of ovarian cancers are diagnosed, coupled with the low and variable response of advanced tumors to standard chemotherapies. To date, clinically useful predictors of treatment response remain lacking. Identifying the genetic determinants of ovarian cancer survival and treatment response is crucial to the development of prognostic biomarkers and personalized therapies that may improve outcomes for the late-stage patients who comprise the majority of cases.Methods
To identify constitutional genetic variations contributing to ovarian cancer mortality, we systematically investigated associations between germline polymorphisms and ovarian cancer survival using data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox proportional hazards regression, we examined 650,000 SNP loci for association with survival. We additionally examined whether the association of significant SNPs with survival was modified by somatic alterations.Results
Germline polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were associated with stage-adjusted survival ( = 1.12e-07 and 1.80e-07, FDR = 1.2e-04 and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally identified as significant in the exome sequencing data; it is in near-perfect LD with rs4934282. The associations with survival remained significant when somatic alterations.Conclusions
Discovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies. 相似文献14.
Larson Boundenga Boris Makanga Benjamin Ollomo Aude Gilabert Virginie Rougeron Bertrand Mve-Ondo Céline Arnathau Patrick Durand Nancy Diamella Moukodoum Alain-Prince Okouga Lucresse Delicat-Loembet Lauriane Yacka-Mouele Nil Rahola Eric Leroy Cheikh Tidiane BA Francois Renaud Franck Prugnolle Christophe Paupy 《PloS one》2016,11(2)
Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes. 相似文献
15.
Claire E Naylor Claire Bagnéris Paul G DeCaen Altin Sula Antonella Scaglione David E Clapham BA Wallace 《The EMBO journal》2016,35(8):820-830
Voltage‐gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na+ ≈ Li+ ≫ K+, Ca2+, Mg2+) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones. 相似文献
16.
17.
Sauro HM Hucka M Finney A Wellock C Bolouri H Doyle J Kitano H 《Omics : a journal of integrative biology》2003,7(4):355-372
Researchers in quantitative systems biology make use of a large number of different software packages for modelling, analysis, visualization, and general data manipulation. In this paper, we describe the Systems Biology Workbench (SBW), a software framework that allows heterogeneous application components--written in diverse programming languages and running on different platforms--to communicate and use each others' capabilities via a fast binary encoded-message system. Our goal was to create a simple, high performance, opensource software infrastructure which is easy to implement and understand. SBW enables applications (potentially running on separate, distributed computers) to communicate via a simple network protocol. The interfaces to the system are encapsulated in client-side libraries that we provide for different programming languages. We describe in this paper the SBW architecture, a selection of current modules, including Jarnac, JDesigner, and SBWMeta-tool, and the close integration of SBW into BioSPICE, which enables both frameworks to share tools and compliment and strengthen each others capabilities. 相似文献
18.
van der Veen BA Uitdehaag JC Dijkstra BW Dijkhuizen L 《Biochimica et biophysica acta》2000,1543(2):336-360
19.
Klaesner Joseph W.; Pou N. Adrienne; Parker Richard E.; Finney Charlene; Roselli Robert J. 《Journal of applied physiology》1998,84(4):1381-1387
In this study, lung filtration coefficient(Kfc) wasmeasured in eight isolated canine lung preparations by using threemethods: standard gravimetric (Std), blood-corrected gravimetric (BC), and optical. The lungs were held in zone III conditions and were subjected to an average venous pressure increase of 8.79 ± 0.93 (mean ± SD) cmH2O. Thepermeability of the lungs was increased with an infusion of alloxan (75 mg/kg). The resultingKfc values (inmilliliters · min1 · cmH2O1 · 100 g dry lung weight1)measured by using Std and BC gravimetric techniques before vs. afteralloxan infusion were statistically different: Std, 0.527 ± 0.290 vs. 1.966 ± 0.283; BC, 0.313 ± 0.290 vs. 1.384 ± 0.290. However, the optical technique did not show any statisticaldifference between pre- and postinjury with alloxan, 0.280 ± 0.305 vs. 0.483 ± 0.297, respectively. The alloxan injury, quantified byusing multiple-indicator techniques, showed an increase in permeability and a corresponding decrease in reflection coefficient for albumin (f). Because the opticalmethod measures the product ofKfc and f, this study shows thatalbumin should not be used as an intravascular optical filtrationmarker when permeability is elevated. However, the optical technique,along with another means of measuringKfc (such as BC),can be used to calculate the fof a tracer (in this study, fof 0.894 at baseline and 0.348 after injury). Another important findingof this study was that the ratio of baseline-to-injury Kfc values wasnot statistically different for Std and BC techniques, indicating thatthe percent contribution of slow blood-volume increases does not changebecause of injury. 相似文献
20.
Malaria and HIV co-infection is a growing health priority. However, most research on malaria or HIV currently focuses on each infection individually. Although understanding the disease dynamics for each of these pathogens independently is vital, it is also important that the interactions between these pathogens are investigated and understood. We have developed a versatile in vitro model of HIV-malaria co-infection to study host immune responses to malaria in the context of HIV infection. Our model allows the study of secreted factors in cellular supernatants, cell surface and intracellular protein markers, as well as RNA expression levels. The experimental design and methods used limit variability and promote data reliability and reproducibility. All pathogens used in this model are natural human pathogens (Plasmodium falciparum and HIV-1), and all infected cells are naturally infected and used fresh. We use human erythrocytes parasitized with P. falciparum and maintained in continuous in vitro culture. We obtain freshly isolated peripheral blood mononuclear cells from chronically HIV-infected volunteers. Every condition used has an appropriate control (P. falciparum parasitized vs. normal erythrocytes), and every HIV-infected donor has an HIV uninfected control, from which cells are harvested on the same day. This model provides a realistic environment to study the interactions between malaria parasites and human immune cells in the context of HIV infection. 相似文献