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101.
Yu ET Hawkins A Kuntz ID Rahn LA Rothfuss A Sale K Young MM Yang CL Pancerella CM Fabris D 《Journal of proteome research》2008,7(11):4848-4857
Modern biomedical research is evolving with the rapid growth of diverse data types, biophysical characterization methods, computational tools and extensive collaboration among researchers spanning various communities and having complementary backgrounds and expertise. Collaborating researchers are increasingly dependent on shared data and tools made available by other investigators with common interests, thus forming communities that transcend the traditional boundaries of the single research laboratory or institution. Barriers, however, remain to the formation of these virtual communities, usually due to the steep learning curve associated with becoming familiar with new tools, or with the difficulties associated with transferring data between tools. Recognizing the need for shared reference data and analysis tools, we are developing an integrated knowledge environment that supports productive interactions among researchers. Here we report on our current collaborative environment, which focuses on bringing together structural biologists working in the area of mass spectrometric based methods for the analysis of tertiary and quaternary macromolecular structures (MS3D) called the Collaboratory for MS3D (C-MS3D). C-MS3D is a Web-portal designed to provide collaborators with a shared work environment that integrates data storage and management with data analysis tools. Files are stored and archived along with pertinent meta data in such a way as to allow file handling to be tracked (data provenance) and data files to be searched using keywords and modification dates. While at this time the portal is designed around a specific application, the shared work environment is a general approach to building collaborative work groups. The goal of this is to not only provide a common data sharing and archiving system, but also to assist in the building of new collaborations and to spur the development of new tools and technologies. 相似文献
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104.
Malin Sandström Anders Lansner Jeanette Hellgren-Kotaleski Jean-Pierre Rospars 《Journal of computational neuroscience》2009,27(3):337-355
We modeled the firing rate of populations of olfactory receptor neurons (ORNs) responding to an odorant at different concentrations.
Two cases were considered: a population of ORNs that all express the same olfactory receptor (OR), and a population that expresses
many different ORs. To take into account ORN variability, we replaced single parameter values in a biophysical ORN model with
values drawn from statistical distributions, chosen to correspond to experimental data. For ORNs expressing the same OR, we
found that the distributions of firing frequencies are Gaussian at all concentrations, with larger mean and standard deviation
at higher concentrations. For a population expressing different ORs, the distribution of firing frequencies can be described
as the superposition of a Gaussian distribution and a lognormal distribution. Distributions of maximum value and dynamic range
of spiking frequencies in the simulated ORN population were similar to experimental results. 相似文献
105.
Effect of Tree Species and Mycorrhizal Colonization on the Archaeal Population of Boreal Forest Rhizospheres
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Group 1.1c Crenarchaeota are the predominating archaeal group in acidic boreal forest soils. In this study, we show that the detection frequency of 1.1c crenarchaeotal 16S rRNA genes in the rhizospheres of the boreal forest trees increased following colonization by the ectomycorrhizal fungus Paxillus involutus. This effect was very clear in the fine roots of Pinus sylvestris, Picea abies, and Betula pendula, the most common forest trees in Finland. The nonmycorrhizal fine roots had a clearly different composition of archaeal 16S rRNA genes in comparison to the mycorrhizal fine roots. In the phylogenetic analysis, the 1.1c crenarchaeotal 16S rRNA gene sequences obtained from the fine roots formed a well-defined cluster separate from the mycorrhizal ones. Alnus glutinosa differed from the other trees by having high diversity and detection levels of Crenarchaeota both on fine roots and on mycorrhizas as well as by harboring a distinct archaeal flora. The similarity of the archaeal populations in rhizospheres of the different tree species was increased upon colonization by the ectomycorrhizal fungus. A minority of the sequences obtained from the mycorrhizas belonged to Euryarchaeota (order Halobacteriales). 相似文献
106.
Angela M. Zivkovic Michelle M. Wiest UyenThao Nguyen Malin L. Nording Steven M. Watkins J. Bruce German 《Metabolomics : Official journal of the Metabolomic Society》2009,5(2):209-218
The development of assessment techniques with immediate clinical applicability is a priority for resolving the growing epidemic
in metabolic disease. Many imbalances in diet-dependent metabolism are not detectable in the fasted state. Resolving the high
inter-individual variability in response to diet requires the development of techniques that can detect metabolic dysfunction
at the level of the individual. The intra- and inter-individual variation in lipid metabolism in response to a standardized
test meal was determined. Following an overnight fast on three different days, three healthy subjects consumed a test meal
containing 40% of their daily calories. Plasma samples were collected at fasting, and 1, 3, 6, and 8 h after the test meal.
Plasma fatty acid (FA) concentrations within separated lipid classes and lipoprotein fractions were measured at each time
point. The intra-individual variation within each subject across three days was lower than the inter-individual differences
among the three subjects for over 50% of metabolites in the triacylglycerol (TG), FA, and phosphatidylcholine (PC) lipid classes
at 6 h, and for 25–50% of metabolites across lipid classes at 0, 1, 3, and 8 h. The consistency of response within individuals
was visualized by principal component analysis (PCA) and confirmed by ANOVA. Three representative metabolites that discriminated
among the three individuals in the apolipoprotein B (ApoB) fraction, TG16:1n7, TG18:2n6, and PC18:3n3, are discussed in detail.
The postprandial responses of individuals were unique within metabolites that were individual discriminators (ID) of metabolic
phenotype. This study shows that the targeted metabolomic measurement of individual metabolic phenotype in response to a specially
formulated lipid challenge is possible even without lead-in periods, dietary and lifestyle control, or intervention over a
3-month period in healthy free-living individuals. 相似文献
107.
Ivan Dimitrijevic Marie-Louise Edvinsson Qingwen Chen Malin Malmsjö Per-Ola Kimblad Lars Edvinsson 《BMC cardiovascular disorders》2009,9(1):1-11
Background
Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease.Methods
Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro pharmacology.Results
ETA and, to a lesser extent, ETB receptor staining was observed in the healthy vascular smooth muscle cells. The level of ETB receptor expression was higher in patients undergoing CABG surgery (250% ± 23%; P < 0.05) and in the patients with angina pectoris (199% ± 6%; P < 0.05), than in the healthy controls (100% ± 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ETB receptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ETA receptors. AT1 and, to a lesser extent, AT2 receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT1 receptor expression was higher in both the angina pectoris (128% ± 25%; P < 0.05) and in the CABG patients (203% ± 41%; P < 0.05), as compared to the healthy controls (100% ± 25%). The increased AT1 receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s).Conclusion
The results demonstrate, for the first time, upregulation of ETB and AT1 receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions. 相似文献108.
Sara Lindstr?m Malin Eriksson Tandis Vazin Julia Sandberg Joakim Lundeberg Jonas Frisén Helene Andersson-Svahn 《PloS one》2009,4(9)
With recent findings on the role of reprogramming factors on stem cells, in vitro screening assays for studying (de)-differentiation is of great interest. We developed a miniaturized stem cell screening chip that is easily accessible and provides means of rapidly studying thousands of individual stem/progenitor cell samples, using low reagent volumes. For example, screening of 700,000 substances would take less than two days, using this platform combined with a conventional bio-imaging system. The microwell chip has standard slide format and consists of 672 wells in total. Each well holds 500 nl, a volume small enough to drastically decrease reagent costs but large enough to allow utilization of standard laboratory equipment. Results presented here include weeklong culturing and differentiation assays of mouse embryonic stem cells, mouse adult neural stem cells, and human embryonic stem cells. The possibility to either maintain the cells as stem/progenitor cells or to study cell differentiation of stem/progenitor cells over time is demonstrated. Clonality is critical for stem cell research, and was accomplished in the microwell chips by isolation and clonal analysis of single mouse embryonic stem cells using flow cytometric cell-sorting. Protocols for practical handling of the microwell chips are presented, describing a rapid and user-friendly method for the simultaneous study of thousands of stem cell cultures in small microwells. This microwell chip has high potential for a wide range of applications, for example directed differentiation assays and screening of reprogramming factors, opening up considerable opportunities in the stem cell field. 相似文献
109.
Kerstin Svensson Malin Granberg Linda Karlsson Vera Neubauerova Mats Forsman Anders Johansson 《PloS one》2009,4(12)
A robust, rapid and flexible real-time PCR assay for hierarchical genetic typing of clinical and environmental isolates of Francisella is presented. Typing markers were found by multiple genome and gene comparisons, from which 23 canonical single nucleotide polymorphisms (canSNPs) and 11 canonical insertion-deletion mutations (canINDELs) were selected to provide phylogenetic guidelines for classification from genus to isolate level. The specificity of the developed assay, which uses 68 wells of a 96-well real-time PCR format with a detection limit of 100 pg DNA, was assessed using 62 Francisella isolates of diverse genetic and geographical origins. It was then successfully used for typing 14 F. tularensis subsp. holarctica isolates obtained from tularemia patients in Sweden in 2008 and five more genetically diverse Francisella isolates of global origins. When applied to human ulcer specimens for direct pathogen detection the results were incomplete due to scarcity of DNA, but sufficient markers were identified to detect fine-resolution differences among F. tularensis subsp. holarctica isolates causing infection in the patients. In contrast to other real-time PCR assays for Francisella, which are typically designed for specific detection of a species, subspecies, or strain, this type of assay can be easily tailored to provide appropriate phylogenetic and/or geographical resolution to meet the objectives of the analysis. 相似文献
110.
Masterton M Hansson MG Höglund AT 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2010,41(4):340-346
With the advanced methods of analysing old biological material, it is pressing to discuss what should be allowed to be done with human remains, particularly for well documented historical individuals. We argue that Queen Christina of Sweden, who challenged the traditional gender roles, has an interest in maintaining her privacy when there are continued attempts to reveal her ‘true’ gender. In the long-running philosophical debate on posthumous wronging, the fundamental question is: Who is wronged? Our aim is to find this ‘missing subject’ using narrative theory.Narrative identity emphasises the fact that no person is alone in knowing or telling their life story. People’s lives are entangled and parts of the life story of a deceased person can remain in the living realm. Since the narrative identity of a person does not necessarily end upon their death, and this narrative continues to relate directly to the person who once existed, it is the narrative subject that can continue to be posthumously wronged. Queen Christina can no longer maintain her own identity, but we maintain it by our research into her life. We propose three duties relevant for posthumous wronging: the duty of truthfulness, the duty of recognition and the duty to respect privacy. 相似文献