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91.
Ashley Erin Clark 《The Yale journal of biology and medicine》2012,85(3):421-424
Now in its 8th year, the Yale Healthcare Conference has arguably come upon its
most exciting and dramatic time within the U.S. health care system. Dynamic
speakers from all over the country came together in April 2012 at Yale
University to question, debate, creatively think, and examine challenges within
health care organizations and institutions. One of the most prominent issues
concerned the aftermath of sequencing the human genome and the explosion of
information concerning gene polymorphisms and biomarkers in health and disease.
Clinicians, scientists, and pharmaceuticals are looking to innovative
individually tailored treatments for patients. During the conference breakout
session, speakers Thomas Lynch, MD, director of the Yale Cancer Center and
physician-in-chief of the Smilow Cancer Hospital, and Zen Chu, MBA, co-founder
of Accelerated Medical Ventures and entrepreneur-in-residence at Massachusetts
Institute of Technology, provided enriching discussion on the delivery of
science and genetic care of the individual. 相似文献
92.
Small-Howard A Morozova N Stoytcheva Z Forry EP Mansell JB Harney JW Carlson BA Xu XM Hatfield DL Berry MJ 《Molecular and cellular biology》2006,26(6):2337-2346
Selenocysteine incorporation in eukaryotes occurs cotranslationally at UGA codons via the interactions of RNA-protein complexes, one comprised of selenocysteyl (Sec)-tRNA([Ser]Sec) and its specific elongation factor, EFsec, and another consisting of the SECIS element and SECIS binding protein, SBP2. Other factors implicated in this pathway include two selenophosphate synthetases, SPS1 and SPS2, ribosomal protein L30, and two factors identified as binding tRNA([Ser]Sec), termed soluble liver antigen/liver protein (SLA/LP) and SECp43. We report that SLA/LP and SPS1 interact in vitro and in vivo and that SECp43 cotransfection increases this interaction and redistributes all three proteins to a predominantly nuclear localization. We further show that SECp43 interacts with the selenocysteyl-tRNA([Ser]Sec)-EFsec complex in vitro, and SECp43 coexpression promotes interaction between EFsec and SBP2 in vivo. Additionally, SECp43 increases selenocysteine incorporation and selenoprotein mRNA levels, the latter presumably due to circumvention of nonsense-mediated decay. Thus, SECp43 emerges as a key player in orchestrating the interactions and localization of the other factors involved in selenoprotein biosynthesis. Finally, our studies delineating the multiple, coordinated protein-nucleic acid interactions between SECp43 and the previously described selenoprotein cotranslational factors resulted in a model of selenocysteine biosynthesis and incorporation dependent upon both cytoplasmic and nuclear supramolecular complexes. 相似文献
93.
Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia
Moreno-De-Luca D;SGENE Consortium Mulle JG;Simons Simplex Collection Genetics Consortium Kaminsky EB Sanders SJ;GeneSTAR Myers SM Adam MP Pakula AT Eisenhauer NJ Uhas K Weik L Guy L Care ME Morel CF Boni C Salbert BA Chandrareddy A Demmer LA Chow EW Surti U Aradhya S Pickering DL Golden DM Sanger WG Aston E Brothman AR Gliem TJ Thorland EC Ackley T Iyer R Huang S Barber JC Crolla JA Warren ST Martin CL Ledbetter DH 《American journal of human genetics》2010,87(5):618-630
Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10−5). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only. 相似文献
94.
Brian K. Hand Sam A. Cushman Erin L. Landguth John Lucotch 《Biodiversity and Conservation》2014,23(11):2761-2779
Quantifying the effects of landscape change on population connectivity is compounded by uncertainties about population size and distribution and a limited understanding of dispersal ability for most species. In addition, the effects of anthropogenic landscape change and sensitivity to regional climatic conditions interact to strongly affect habitat fragmentation and loss. To further develop conservation theory and to understand the interplay between all of these factors, we simulated habitat fragmentation and loss across the Western United States for several hypothetical species associated with four biome types, and a range of habitat requirements and dispersal abilities. We found dispersal ability and population size of the focal species to be equally sensitive to habitat extent, while dispersal ability is more sensitive to habitat fragmentation. There were also strong critical threshold effects where habitat connectivity decreased disproportionately to decreases in life-history traits making these species near these thresholds more sensitive to changes in habitat loss and fragmentation. Overall, grassland and forest associated species are also most at risk from habitat loss and fragmentation driven by human related land-use. These two largest biome types were most sensitive at large contiguous patch sizes which is often considered most important for metapopulation viability and biodiversity conservation. Hypothetical simulation studies such as this can be of great value to scientists in further conceptualizing and developing conservation theory, and evaluating spatially-explicit scenarios of habitat connectivity. Our results are available for download in a web-based interactive mapping prototype useful for accessing the results of this study. 相似文献
95.
96.
The structure of the lipopolysaccharide core of Vibrio vulnificus type strain 27562 is presented. LPS hydrolysis gave two oligosaccharides, OS-1 and OS-2, as well as lipid A. NMR spectroscopic data corresponded to the presence of one Kdo residue, one β-glucopyranose, three heptoses, one glyceric acid, one acetate, three PEtN, and one 5,7-diacylamido-3,5,7,9-tetradeoxynonulosonic acid residue (pseudaminic acid, Pse) in OS1. OS2 differed form OS 1 by the absence of glyceric acid, acetate, and Pse residues. Lipid A was analyzed for fatty acid composition and the following fatty acids were found: C14:0, C12:0-3OH, C16:0, C16:1, C14:0-3OH, C18:0, C18:1 in a ratio of 1:3:3:1:2.5:0.6:0.8. 相似文献
97.
Erin Conlisk John Conlisk Brian Enquist Jill Thompson John Harte 《Global Ecology and Biogeography》2009,18(1):1-10
Aim Many ecological surveys record only the presence or absence of species in the cells of a rectangular grid. Ecologists have investigated methods for using these data to predict the total abundance of a species from the number of grid cells in which the species is present. Our aim is to improve such predictions by taking account of the spatial pattern of occupied cells, in addition to the number of occupied cells.
Innovation We extend existing prediction models to include a spatial clustering variable. The extended models can be viewed as combining two macroecological regularities, the abundance–occupancy regularity and a spatial clustering regularity. The models are estimated using data from five tropical forest censuses, including three Panamanian censuses (4, 6 and 50 ha), one Costa Rican census (16 ha) and one Puerto Rican census (16 ha). A serpentine grassland census (8 × 8 m) from northern California is also studied.
Main conclusions Taking account of the spatial clustering of occupied cells improves abundance prediction from presence–absence data, reducing the mean square error of log-predictions by roughly 54% relative to a benchmark Poisson predictor and by roughly 34% relative to current prediction methods. The results have high statistical significance. 相似文献
Innovation We extend existing prediction models to include a spatial clustering variable. The extended models can be viewed as combining two macroecological regularities, the abundance–occupancy regularity and a spatial clustering regularity. The models are estimated using data from five tropical forest censuses, including three Panamanian censuses (4, 6 and 50 ha), one Costa Rican census (16 ha) and one Puerto Rican census (16 ha). A serpentine grassland census (8 × 8 m) from northern California is also studied.
Main conclusions Taking account of the spatial clustering of occupied cells improves abundance prediction from presence–absence data, reducing the mean square error of log-predictions by roughly 54% relative to a benchmark Poisson predictor and by roughly 34% relative to current prediction methods. The results have high statistical significance. 相似文献
98.
Subarna Bhattacharya Paul W. Burridge Erin M. Kropp Sandra L. Chuppa Wai-Meng Kwok Joseph C. Wu Kenneth R. Boheler Rebekah L. Gundry 《Journal of visualized experiments : JoVE》2014,(91)
There is an urgent need to develop approaches for repairing the damaged heart, discovering new therapeutic drugs that do not have toxic effects on the heart, and improving strategies to accurately model heart disease. The potential of exploiting human induced pluripotent stem cell (hiPSC) technology to generate cardiac muscle “in a dish” for these applications continues to generate high enthusiasm. In recent years, the ability to efficiently generate cardiomyogenic cells from human pluripotent stem cells (hPSCs) has greatly improved, offering us new opportunities to model very early stages of human cardiac development not otherwise accessible. In contrast to many previous methods, the cardiomyocyte differentiation protocol described here does not require cell aggregation or the addition of Activin A or BMP4 and robustly generates cultures of cells that are highly positive for cardiac troponin I and T (TNNI3, TNNT2), iroquois-class homeodomain protein IRX-4 (IRX4), myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v) and myosin regulatory light chain 2, atrial isoform (MLC2a) by day 10 across all human embryonic stem cell (hESC) and hiPSC lines tested to date. Cells can be passaged and maintained for more than 90 days in culture. The strategy is technically simple to implement and cost-effective. Characterization of cardiomyocytes derived from pluripotent cells often includes the analysis of reference markers, both at the mRNA and protein level. For protein analysis, flow cytometry is a powerful analytical tool for assessing quality of cells in culture and determining subpopulation homogeneity. However, technical variation in sample preparation can significantly affect quality of flow cytometry data. Thus, standardization of staining protocols should facilitate comparisons among various differentiation strategies. Accordingly, optimized staining protocols for the analysis of IRX4, MLC2v, MLC2a, TNNI3, and TNNT2 by flow cytometry are described. 相似文献
99.
Phytoplankton assemblages across the marine to low-salinity transition zone in a blackwater dominated estuary 总被引:1,自引:0,他引:1
Along the salinity gradient between the freshwater reach ofthe Suwannee River and the marine waters of the Gulf of Mexico,the spatial and temporal composition and abundance of phytoplanktonwas examined in relation to physical and chemical water-columnvariables (i.e. salinity, nutrient and light availability andtemperature). The goal of this study was to explore the applicabilityof the concepts of ecotone and ecocline to the distributionof phytoplankton. This was undertaken in a relatively open estuarydominated by a tannin-colored river, the Suwannee River, alongthe central northwest coast of Florida, USA. Hierarchical clusteranalysis and non-metric multi-dimensional scaling (MDS) wasused to define biologically distinct regions within the estuarybased on the composition of phytoplankton. Variations in phytoplanktonassemblages in relation to environmental variables were investigatedusing a canonical correspondence analysis. The results indicatethat in addition to the alignment of phytoplankton compositionalong a salinity gradient, several key environmental factorsinfluence phytoplankton assemblages within hydrologically distinctregions of the estuary supporting an ecocline view. However,the distribution of dinoflagellate assemblages were in contrastto the more temporally fluid spatial distributions of cyanobacteriaand diatoms in the Suwannee River estuary. The spatially definednature of the dinoflagellate assemblages was more characteristicof an ecotone rather than an ecocline. 相似文献
100.