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61.
Two forward genetic screens for vein density mutants in sorghum converge on a cytochrome P450 gene in the brassinosteroid pathway 下载免费PDF全文
Govinda Rizal Vivek Thakur Jacqueline Dionora Shanta Karki Samart Wanchana Kelvin Acebron Nikki Larazo Richard Garcia Abigail Mabilangan Florencia Montecillo Florence Danila Reychelle Mogul Paquito Pablico Hei Leung Jane A. Langdale John Sheehy Steven Kelly William Paul Quick 《The Plant journal : for cell and molecular biology》2015,84(2):257-266
The specification of vascular patterning in plants has interested plant biologists for many years. In the last decade a new context has emerged for this interest. Specifically, recent proposals to engineer C4 traits into C3 plants such as rice require an understanding of how the distinctive venation pattern in the leaves of C4 plants is determined. High vein density with Kranz anatomy, whereby photosynthetic cells are arranged in encircling layers around vascular bundles, is one of the major traits that differentiate C4 species from C3 species. To identify genetic factors that specify C4 leaf anatomy, we generated ethyl methanesulfonate‐ and γ‐ray‐mutagenized populations of the C4 species sorghum (Sorghum bicolor), and screened for lines with reduced vein density. Two mutations were identified that conferred low vein density. Both mutations segregated in backcrossed F2 populations as homozygous recessive alleles. Bulk segregant analysis using next‐generation sequencing revealed that, in both cases, the mutant phenotype was associated with mutations in the CYP90D2 gene, which encodes an enzyme in the brassinosteroid biosynthesis pathway. Lack of complementation in allelism tests confirmed this result. These data indicate that the brassinosteroid pathway promotes high vein density in the sorghum leaf, and suggest that differences between C4 and C3 leaf anatomy may arise in part through differential activity of this pathway in the two leaf types. 相似文献
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Letizia Cito Paola Indovina Iris Maria Forte Francesca Pentimalli Domenico Di Marzo Pasquale Somma Daniela Barone Antonella Penon Danila Penon Elisa Ceccherini Pietro Micheli Luca Saragoni Marina Di Domenico Antonia Feola Franco Roviello Eliseo Mattioli Antonio Giordano 《Journal of cellular physiology》2015,230(4):802-805
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Giovanna Pescatore Danila Branca Fabrizio Fiore Olaf Kinzel Laura Llauger Bufi Ester Muraglia Federica Orvieto Michael Rowley Carlo Toniatti Caterina Torrisi Philip Jones 《Bioorganic & medicinal chemistry letters》2010,20(3):1094-1099
Herein we describe the discovery of a novel series of pyrrolo[1,2-a]pyrazin-1(2H)-one PARP inhibitors. Optimization led to compounds that display excellent PARP-1 enzyme potency and inhibit the proliferation of BRCA deficient cells in the low double-digit nanomolar range showing excellent selectivity over BRCA proficient cancer cells. 相似文献
64.
Evidence of post‐glacial secondary contact and subsequent anthropogenic influence on the genetic composition of Fennoscandian moose (Alces alces) 下载免费PDF全文
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Wael Harb Andrea Fan Tony Tran Daniel C. Danila David Keys Michael Schwartz Cristian Ionescu-Zanetti 《Translational oncology》2013,6(5):528-IN1
Circulating tumor cells (CTCs) provide a readily accessible source of tumor material from patients with cancer. Molecular profiling of these rare cells can lead to insight on disease progression and therapeutic strategies. A critical need exists to isolate CTCs with sufficient quantity and sample integrity to adapt to conventional analytical techniques. We present a microfluidic platform (IsoFlux) that uses flow control and immunomagnetic capture to enhance CTC isolation. A novel cell retrieval mechanism ensures complete transfer of CTCs into the molecular assay. Improved sensitivity to the capture antigen was demonstrated by spike-in experiments for three cell lines of varying levels of antigen expression. We obtained spike-in recovery rates of 74%, 75%, and 85% for MDA-MB-231 (low), PC3 (middle), and SKBR3 (high) cell lines. Recovery using matched enumeration protocols and matched samples (PC3) yielded 90% and 40% recovery for the IsoFlux and CellSearch systems, respectively. In matched prostate cancer samples (N = 22), patients presenting more than four CTCs per blood draw were 95% and 36% using IsoFlux and CellSearch, respectively. An assay for detecting KRAS mutations was described along with data from patients with colorectal cancer, of which 87% presented CTCs above the assay's limit of detection (four CTCs). The CTC KRAS mutant rate was 50%, with 46% of patients displaying a CTC KRAS mutational status that differed from the previously acquired tissue biopsy data. The microfluidic system and mutation assay presented here provide a complete workflow to track oncogene mutational changes longitudinally with high success rates. 相似文献
67.
Camilla Krakstad Even Birkeland Danila Seidel Kanthida Kusonmano Kjell Petersen Siv Mj?s Erling A. Hoivik Elisabeth Wik Mari Kylles? Halle Anne M. ?yan Karl-Henning Kalland Henrica Maria Johanna Werner Jone Trovik Helga Salvesen 《PloS one》2012,7(12)
Background
Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with metastatic endometrial carcinoma. In order to improve treatment, underlying molecular characteristics of primary and metastatic disease must be explored.Methodology/Principal Findings
We utilized the mass spectrometric-based mutation detection technology OncoMap to define the types and frequency of point somatic mutations in endometrial cancer. 67 primary tumors, 15 metastases corresponding to 7 of the included primary tumors and 11 endometrial cancer cell lines were screened for point mutations in 28 known oncogenes. We found that 27 (40.3%) of 67 primary tumors harbored one or more mutations with no increase in metastatic lesions. FGFR2, KRAS and PIK3CA were consistently the most frequently mutated genes in primary tumors, metastatic lesions and cell lines.Conclusions/Significance
Our results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies. 相似文献68.
Danila Boytsov Christof Hannesschlaeger Andreas Horner Christine Siligan Peter Pohl 《Biotechnology journal》2020,15(7)
Measurements of the unitary hydraulic conductivity of membrane channels, pf, may be hampered by difficulties in producing sufficient quantities of purified and reconstituted proteins. Low yield expression, the purely empiric choice of detergents, as well as protein aggregation and misfolding during reconstitution may result in an average of less than one reconstituted channel per large unilamellar vesicle. This limits their applicability for pf measurements, independent of whether light scattering or fluorescence quenching of encapsulated dyes is monitored. Here the micropipette aspiration technique is adopted because its superb sensitivity allows resolving pf values for one order of magnitude smaller protein densities in sphingomyelin and cholesterol rich giant unilamellar vesicles (GUVs). Protein density is derived from intensity fluctuations that fluorescently labeled channels in the aspirated GUV induce by diffusing through the diffraction limited spot. A perfusion system minimizes unstirred layers in the immediate membrane vicinity as demonstrated by the distribution of both encapsulated and extravesicular aqueous dyes. pf amounted to 2.4 ± 0.1 × 10?13 cm³ s?1 for aquaporin‐1 that served as a test case. The new assay paves the way for directly monitoring the effect that interaction of aquaporins with other proteins or inhibitors may have on pf on a single sample. 相似文献
69.
Danila?Vella Italo?Zoppis Giancarlo?Mauri Pierluigi?Mauri Dario?Di SilvestreEmail author 《EURASIP Journal on Bioinformatics and Systems Biology》2017,2017(1):6
The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis. 相似文献
70.
Paula I Burgos Zenoria L Causey Ashutosh Tamhane James M Kelley Elizabeth E Brown Laura B Hughes Maria I Danila Amalia van Everdingen Doyt L Conn Beth L Jonas Leigh F Callahan Edwin A Smith Richard D Brasington Jr Larry W Moreland Désirée M van der Heijde Graciela S Alarcón S Louis Bridges Jr 《Arthritis research & therapy》2010,12(3):1-7