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Parallel analysis of genetic selections using whole genome oligonucleotide arrays 总被引:9,自引:0,他引:9 下载免费PDF全文
Raymond J. Cho Micheline Fromont-Racine Lisa Wodicka Becket Feierbach Timothy Stearns Pierre Legrain David J. Lockhart Ronald W. Davis 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(7):3752-3757
Thousands of genes have recently been sequenced in organisms ranging from Escherichia coli to human. For the majority of these genes, however, available sequence does not define a biological role. Efficient functional characterization of these genes requires strategies for scaling genetic analyses to the whole genome level. Plasmid-based library selections are an established approach to the functional analysis of uncharacterized genes and can help elucidate biological function by identifying, for example, physical interactors for a gene and genetic enhancers and suppressors of mutant phenotypes. The application of these selections to every gene in a eukaryotic genome, however, is generally limited by the need to manipulate and sequence hundreds of DNA plasmids. We present an alternative approach in which identification of nucleic acids is accomplished by direct hybridization to high-density oligonucleotide arrays. Based on the complete sequence of Saccharomyces cerevisiae, high-density arrays containing oligonucleotides complementary to every gene in the yeast genome have been designed and synthesized. Two-hybrid protein–protein interaction screens were carried out for S. cerevisiae genes implicated in mRNA splicing and microtubule assembly. Hybridization of labeled DNA derived from positive clones is sufficient to characterize the results of a screen in a single experiment, allowing rapid determination of both established and previously unknown biological interactions. These results demonstrate the use of oligonucleotide arrays for the analysis of two-hybrid screens. This approach should be generally applicable to the analysis of a range of genetic selections. 相似文献
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Musab S. Hommos An S. De Vriese Mariam P. Alexander Sanjeev Sethi Lisa Vaughan Ladan Zand Kharmen Bharucha Nicola Lepori Andrew D. Rule Fernando C. Fervenza 《Mayo Clinic proceedings. Mayo Clinic》2017,92(12):1772-1781
Objectives
To describe the change in the incidence rates of primary and secondary focal segmental glomerulosclerosis (FSGS) from 1994 through 2013 in Olmsted County, Minnesota, and to identify the clinical and biopsy characteristics that distinguish primary from secondary FSGS.Patients and Methods
Olmsted County adult residents with native kidney biopsy from January 1, 1994, through December 31, 2013, and FSGS as the only glomerulopathy were identified. The clinical and pathologic characterstics of primary and secondary FSGS were described and compared, and incidence rates were calculated.Results
Of 370 adults biopsied, 281 had glomerular diseases, of which 46 (16%) had FSGS. From 1994-2003 to 2004-2013, there were significant increases in kidney biopsy rates (14.7 [95% CI, 12.1-17.3] vs 22.9 [95% CI, 20.0-25.7] per 100,000 person-years, 17% increase per 5 years; P<.001) and total FSGS rates (1.4 [95% CI, 0.6-2.2] vs 3.2 [95% CI, 2.1-4.3] per 100,000 person-years, 41% increase per 5 years; P=.02). Compared with patients with limited foot process effacement (<80%), patients with diffuse effacement (≥80%) without an identifiable cause had lower serum albumin levels (P<.001), had higher proteinuria (P<.001), and were more likely to have nephrotic syndrome (100% vs 4%; P<.001). Patients with diffuse effacement without an identifiable cause were classified as primary FSGS, which accounted for 3 of 12 patients (25%) during 1994-2003 and 9 of 34 (26%) during 2004-2013.Conclusion
Although the incidence of FSGS has increased, the proportions of primary and secondary FSGS have remained stable. 相似文献995.
Lisa Hopp PhD RN FAAN 《International journal of nursing practice》2015,21(5):683-686
Risk of bias is an inherent quality of primary research and therefore of systematic reviews. This column addresses the Cochrane Collaboration's approach to assessing, risks of bias, the meaning of each, indicators of low, high and uncertain, and ways that risk of bias can be represented in a Cochrane systematic review report. The sources of risk of bias that reviewers evaluate include selection, performance, detection, attrition and reporting bias. Each poses threat to the internal validity of the primary studies and requires the reviewer to judge the level of risk as high, low or unclear. Reviewers need to address how studies of higher risk of bias might impact the pooled effect. 相似文献
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Kuan-Ying A. Huang Pramila Rijal Lisa Schimanski Timothy J. Powell Tzou-Yien Lin John W. McCauley Rodney S. Daniels Alain R. Townsend 《The Journal of clinical investigation》2015,125(7):2631-2645
The selective pressure that drives antigenic changes in influenza viruses is thought to
originate from the human immune response. Here, we have characterized the B cell
repertoire from a previously vaccinated donor whose serum had reduced neutralizing
activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was
markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the
ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed
in childhood, was retained. In vitro selection of virus variants with representative
monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the
Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for
resistance to neutralization by multiple monoclonal antibodies and the donor serum. The
K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of
the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an
antibody response tightly focused on this common surface that is capable of selecting
current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid
replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal
antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in
influenza viruses. 相似文献
999.
Michael S. Kiernan Susanna R. Stevens W.H. Wilson Tang Javed Butler Kevin J. Anstrom Edo Y. Birati Justin L. Grodin Divya Gupta Kenneth B. Margulies Shane LaRue Victor G. Dávila-Román Adrian F. Hernandez Lisa de las Fuentes 《Journal of cardiac failure》2018,24(7):428-438
Background
Poor response to loop diuretic therapy is a marker of risk during heart failure hospitalization. We sought to describe baseline determinants of diuretic response and to further explore the relationship between this response and clinical outcomes.Methods and Results
Patient data from the National Heart, Lung, and Blood Institute Heart Failure Network ROSE-AHF and CARRESS-HF clinical trials were analyzed to determine baseline determinants of diuretic response. Diuretic efficiency (DE) was defined as total 72-hour fluid output per total equivalent loop diuretic dose. Data from DOSE-AHF was then used to determine if these predictors of DE correlated with response to a high- versus low-dose diuretic strategy. At 72 hours, the high-DE group had median fluid output of 9071 ml (interquartile range: 7240–11775) with median furosemide dose of 320 mg (220–480) compared with 8030 ml (6300–9915) and 840 mg (600–1215) respectively for the low DE group. Cystatin C was independently associated with DE (odds ratio 0.36 per 1mg/L increase; 95% confidence interval: 0.24–0.56; P < 0.001). Independently from baseline characteristics, reduced fluid output, weight loss and DE were each associated with increased 60 day mortality. Among patients with estimated glomerular filtration rate below the median, those randomized to a high-dose strategy had improved symptoms compared with those randomized to a low-dose strategy.Conclusions
Elevated baseline cystatin C, as a biomarker of renal dysfunction, is associated with reduced diuretic response during heart failure hospitalization. Higher loop diuretic doses are required for therapeutic decongestion in patients with renal insufficiency. Poor response identifies a high-risk population. 相似文献1000.
A phase I/II trial of vorinostat (SAHA) in combination with rituximab‐CHOP in patients with newly diagnosed advanced stage diffuse large B‐cell lymphoma (DLBCL): SWOG S0806 下载免费PDF全文