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61.
62.
Padhukasahasram B Halperin E Wessel J Thomas DJ Silver E Trumbower H Cargill M Stephan DA 《PloS one》2010,5(12):e14338
The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies. 相似文献
63.
Debajit Saha David Morton Michael Ariel Ralf Wessel 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(2):153-165
The optic tectum holds a central position in the tectofugal pathway of non-mammalian species and is reciprocally connected
with the nucleus isthmi. Here, we recorded from individual nucleus isthmi pars parvocellularis (Ipc) neurons in the turtle
eye-attached whole-brain preparation in response to a range of computer-generated visual stimuli. Ipc neurons responded to
a variety of moving or flashing stimuli as long as those stimuli were small. When mapped with a moving spot, the excitatory
receptive field was of circular Gaussian shape with an average half-width of less than 3°. We found no evidence for directional
sensitivity. For moving spots of varying sizes, the measured Ipc response-size profile was reproduced by the linear Difference-of-Gaussian
model, which is consistent with the superposition of a narrow excitatory center and an inhibitory surround. Intracellular
Ipc recordings revealed a strong inhibitory connection from the nucleus isthmi pars magnocellularis (Imc), which has the anatomical
feature to provide a broad inhibitory projection. The recorded Ipc response properties, together with the modulatory role
of the Ipc in tectal visual processing, suggest that the columns of Ipc axon terminals in turtle optic tectum bias tectal
visual responses to small dark changing features in visual scenes. 相似文献
64.
65.
Wessel Van Leeuwen Marc J. M. Hagendoorn Tom Ruttink Remco Van Poecke Linus H. W. Van Der Plas Alexander R. Van Der Krol 《Plant Molecular Biology Reporter》2000,18(2):143-144
The properties of the firefly luciferase (LUC) make it a very good nondestructive reporter to quantify and image transgene
promoter activity in plants. The short half-life of the LUC mRNA and protein, and the very limited regeneration of the LUC
protein after reacting with luciferin, enables monitoring of changes in gene activity with a high time resolution. However,
the ease at which luciferase activity is measuredin planta, using a light sensitive camera system (2D-luminometer), contrasts sharply with the complications that arise from interpreting
the results. A variegated pattern of luciferase activity, that is often observed inin planta measurements, might either be caused by differences in influx, availability of the substrates (luciferin, oxygen, ATP) or
by local differences in reporter gene activity. Here we tested the possible contribution of differences in the availability
of each substrate to the variegatedin planta luciferase activity, and we show whenin planta luciferase activity is measured under substrate equilibrium conditions and can be related to the promoter activity of the
reporter gene. Furthermore, we demonstrate the effects of protein stability, apparent half-life of luciferase activity, regeneration
of luciferase and pH on thein vivo andin vitro luciferase measurements. The combined results give the prerequisites for the correct utilisation of the luciferase reporter
system, especially forin vivo gene expression studies in plant research. 相似文献
66.
Marcelo Desimone Martina Krüger Tim Wessel Marco Wehofsky Ralf Hoffmann Edgar Wagner 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2000,737(1-2)
Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. Although some aminopeptidase activities have been found in plant chloroplasts, the identity of these proteins remains unclear. In this work, we report the purification to apparent homogeneity of a soluble aminopeptidase from isolated barley chloroplasts which preferentially degraded alanyl-p-nitroanilide (Ala-pNA). After organelle isolation in a density gradient and precipitation of soluble proteins with ammonium sulfate, the proteins were purified in three consecutive steps including hydrophobic interaction, gel permeation and ion-exchange chromatographies. The purified enzyme appeared as a single band with a Mr of 84 000 in sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis. The Mr of the native enzyme was estimated to be 93 000 by gel permeation chromatography, suggesting that the protein is a monomer. Mass spectrometry analysis of tryptic digests indicates that the primary structure of the protein has not been reported previously. The enzyme was characterized as a metalloprotease as it could be totally inhibited by 1,10-phenanthroline. Strong inhibition could also be observed using the specific aminopeptidase inhibitors amastatin and bestatin. Besides Ala-pNA, the purified protein could also cleave with decreasing activity glycyl-pNA, leucyl-pNA, lysyl-pNA, methionyl-pNA and arginyl-pNA. The possible physiological role of this enzyme in the chloroplast stroma is discussed. 相似文献
67.
68.
Xie X Rivier AS Zakrzewicz A Bernimoulin M Zeng XL Wessel HP Schapira M Spertini O 《The Journal of biological chemistry》2000,275(44):34818-34825
Selectins play a major role in the inflammatory reaction by initiating neutrophil attachment to activated vascular endothelium. Some heparin preparations can interact with L- and P-selectin; however, the determinants required for inhibiting selectin-mediated cell adhesion have not yet been characterized. We now report that carboxyl-reduced and sulfated heparin (prepared by chemical modifications of porcine intestinal mucosal heparin leading to the replacement of carboxylates by O-sulfate groups) and trestatin A sulfate (obtained by sulfation of trestatin A, a non-uronic pseudo-nonasaccharide extracted from Streptomyces dimorphogenes) exhibit strong anti-P-selectin and anti-L-selectin activity while lacking antithrombin-mediated anticoagulant activity. In vitro experiments revealed that both compounds inhibited P-selectin- and L-selectin-mediated cell adhesion under laminar flow conditions. Moreover, carboxyl-reduced and sulfated heparin and trestatin A sulfate were also active in vivo, as assessed by experiments showing 1) that microinfusion of trestatin A sulfate reduced by 96% leukocyte rolling along rat mesenteric postcapillary venules and 2) that both compounds inhibited (by 58-81%) neutrophil migration into thioglycollate-inflamed peritoneum of BALB/c mice. These results indicate that nonanticoagulant sulfated saccharides targeted at P-selectin and L-selectin may have therapeutic potential in inflammatory disorders. 相似文献
69.
C. Zühlke Yorck Hellenbroich Franziska Schaaff Ulrike Gehlken Karl Wessel Thomas Schubert Jorge Cervos-Navarro H. Pickartz Eberhard Schwinger 《Human genetics》1997,100(3-4):339-344
Neurodegenerative disorders, including spinocerebellar ataxias (SCA), Huntington disease (HD) and dentatorubral-pallidoluysian
atrophy (DRPLA), are associated with unstable CAG repeats. To investigate the mitotic stability of the repetitive element
in the genes for SCA1, SCA3, HD, and DRPLA we extracted DNA from up to 13 tissue samples from four deceased individuals with
progressive neurological disorders and neuropathological signs. Due to the formalin fixation of some tissues the genomic DNA
was highly degraded and unsuitable for amplification of fragments longer than 150 bp. After size selection and primer extension
preamplification, specific analyses could be performed even for expanded alleles. In all four patients the SCA1 mutation could
be demonstrated, in one case with remarkable somatic heterogeneity of the elongated allele, whereas alleles of the normal
range were stable in all tissues examined.
Received: 3 February 1997 / Accepted: 9 April 1997 相似文献
70.
Sujay S. Kaushal Arthur J. Gold Susana Bernal Tammy A. Newcomer Johnson Kelly Addy Amy Burgin Douglas A. Burns Ashley A. Coble Eran Hood YueHan Lu Paul Mayer Elizabeth C. Minor Andrew W. Schroth Philippe Vidon Henry Wilson Marguerite A. Xenopoulos Thomas Doody Joseph G. Galella Phillip Goodling Katherine Haviland Shahan Haq Barret Wessel Kelsey L. Wood Norbert Jaworski Kenneth T. Belt 《Biogeochemistry》2018,141(3):281-305
In the Anthropocene, watershed chemical transport is increasingly dominated by novel combinations of elements, which are hydrologically linked together as ‘chemical cocktails.’ Chemical cocktails are novel because human activities greatly enhance elemental concentrations and their probability for biogeochemical interactions and shared transport along hydrologic flowpaths. A new chemical cocktail approach advances our ability to: trace contaminant mixtures in watersheds, develop chemical proxies with high-resolution sensor data, and manage multiple water quality problems. We explore the following questions: (1) Can we classify elemental transport in watersheds as chemical cocktails using a new approach? (2) What is the role of climate and land use in enhancing the formation and transport of chemical cocktails in watersheds? To address these questions, we first analyze trends in concentrations of carbon, nutrients, metals, and salts in fresh waters over 100 years. Next, we explore how climate and land use enhance the probability of formation of chemical cocktails of carbon, nutrients, metals, and salts. Ultimately, we classify transport of chemical cocktails based on solubility, mobility, reactivity, and dominant phases: (1) sieved chemical cocktails (e.g., particulate forms of nutrients, metals and organic matter); (2) filtered chemical cocktails (e.g., dissolved organic matter and associated metal complexes); (3) chromatographic chemical cocktails (e.g., ions eluted from soil exchange sites); and (4) reactive chemical cocktails (e.g., limiting nutrients and redox sensitive elements). Typically, contaminants are regulated and managed one element at a time, even though combinations of elements interact to influence many water quality problems such as toxicity to life, eutrophication, infrastructure corrosion, and water treatment. A chemical cocktail approach significantly expands evaluations of water quality signatures and impacts beyond single elements to mixtures. High-frequency sensor data (pH, specific conductance, turbidity, etc.) can serve as proxies for chemical cocktails and improve real-time analyses of water quality violations, identify regulatory needs, and track water quality recovery following storms and extreme climate events. Ultimately, a watershed chemical cocktail approach is necessary for effectively co-managing groups of contaminants and provides a more holistic approach for studying, monitoring, and managing water quality in the Anthropocene. 相似文献