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91.
92.
Rene Daniel Siu-Wah Chung Hong Chen Peter M. C. Wong PhD 《Journal of biomedical science》1998,5(5):383-394
The c-abl proto-oncogene is ubiquitously expressed during mammalian development. Activated forms of c-Abl proteins are oncogenic and have been shown to suppress apoptosis. The biological role of normal c-Abl protein is unknown. In this study, we have introduced c-abl antisense sequences into various hemopoietic cells by retroviral gene transfer. Introduction and expression of the antisense sequence effectively reduced the amount of c-Abl protein in a number of transduced hemopoietic cells, that consequently underwent apoptosis. When factor-dependent cell lines were examined, we observed that the addition of sufficient amounts of growth factors could suppress apoptosis in myeloid but not in lymphoid lines. The ability of myeloid cells to be rescued by growth factors correlated with upregulation of mRNA level of IL-3 receptor subunits. Our data suggest that c-Abl provides an anti-apoptotic signal during mammalian cell growth, and that myeloid and lymphoid cells are different in their resistance to apoptosis. 相似文献
93.
94.
Dorcas M. Kamuya Sally J. Theobald Vicki Marsh Michael Parker Wenzel P. Geissler Sassy C. Molyneux 《PloS one》2015,10(5)
Consent processes have attracted significant research attention over the last decade, including in the global south. Although relevant studies suggest consent is a complex negotiated process involving multiple actors, most guidelines assume consent is a one-off encounter with a clear ‘yes’ or ‘no’ decision. In this paper we explore the concept of ‘silent refusals’, a situation where it is not clear whether potential participants want to join studies or those in studies want to withdraw from research, as they were not actively saying no. We draw on participant observation, in-depth interviews and group discussions conducted with a range of stakeholders in two large community based studies conducted by the KEMRI Wellcome Trust programme in coastal Kenya. We identified three broad inter-related rationales for silent refusals: 1) a strategy to avoid conflicts and safeguard relations within households, - for young women in particular—to appear to conform to the wishes of elders; 2) an approach to maintain friendly, appreciative and reciprocal relationships with fieldworkers, and the broader research programme; and 3) an effort to retain study benefits, either for individuals, whole households or wider communities. That refusals and underlying rationales were silent posed multiple dilemmas for fieldworkers, who are increasingly recognised to play a key interface role between researchers and communities in many settings. Silent refusals reflect and reinforce complex power relations embedded in decisions about research participation, with important implications for consent processes and broader research ethics practice. Fieldworkers need support to reflect upon and respond to the ethically charged environment they work in. 相似文献
95.
Paul Smithson Lia Florey S. Rene Salgado Christine L. Hershey Honorati Masanja Achuyt Bhattarai Alex Mwita Peter D. McElroy Tanzania Malaria Impact Evaluation Research Group 《PloS one》2015,10(11)
Background
Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period.Methods
Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6–59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM.Results
Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains.Conclusion
Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival. 相似文献96.
Richard B. Lanman Stefanie A. Mortimer Oliver A. Zill Dragan Sebisanovic Rene Lopez Sibel Blau Eric A. Collisson Stephen G. Divers Dave S. B. Hoon E. Scott Kopetz Jeeyun Lee Petros G. Nikolinakos Arthur M. Baca Bahram G. Kermani Helmy Eltoukhy AmirAli Talasaz 《PloS one》2015,10(10)
Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital SequencingTM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient’s cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing. 相似文献
97.
Xuemei Zhao Katie Southwick Helene L. Cardasis Yi Du Michael E. Lassman Dan Xie Mohamed El‐Sherbeini Wayne M. Geissler KellyAnn D. Pryor Andreas Verras Margarita Garcia‐Calvo Dong‐Ming Shen Nathan A. Yates Shirly Pinto Ronald C. Hendrickon 《Proteomics》2010,10(15):2882-2886
Prolylcarboxypeptidase (PRCP) is a serine protease that catalyzes the cleavage of C‐terminal amino acids linked to proline in peptides. It is ubiquitously expressed and is involved in regulating blood pressure, proliferation, inflammation, angiogenesis, and weight maintenance. To identify the candidate proximal target engagement markers for PRCP inhibition in the central nervous system, we profiled the peptidome of human cerebrospinal fluid to look for PRCP substrates using a MS‐based in vitro substrate profiling assay. These experiments identified a single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor‐like protein 2. 相似文献
98.
Tenzin Gayden Maria Regueiro Slavica Vujovic Danica Popovic Marija Djuric Oliver Stojkovic Rene J. Herrera 《American journal of physical anthropology》2010,142(3):380-390
Southeastern Europe and, particularly, the Balkan Peninsula are especially useful when studying the mechanisms responsible for generating the current distribution of Paleolithic and Neolithic genetic signals observed throughout Europe. In this study, 404 individuals from Montenegro and 179 individuals from Serbia were typed for 17 Y‐STR loci and compared across 9 Y‐STR loci to geographically targeted previously published collections to ascertain the phylogenetic relationships of populations within the Balkan Peninsula and beyond. We aim to provide information on whether groups in the region represent an amalgamation of Paleolithic and Neolithic genetic substrata, or whether acculturation has played a critical role in the spread of agriculture. We have found genetic markers of Middle Eastern, south Asian and European descent in the area, however, admixture analyses indicate that over 80% of the Balkan gene pool is of European descent. Altogether, our data support the view that the diffusion of agriculture into the Balkan region was mostly a cultural phenomenon although some genetic infiltration from Africa, the Levant, the Caucasus, and the Near East has occurred. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
99.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献100.
Bert Vander Cruyssen Patrick Durez Rene Westhovens Filip De Keyser 《Arthritis research & therapy》2010,12(3):1-8