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981.
Valuable binding-site annotation data are stored in databases. However, several types of errors can, and do, occur in the
process of manually incorporating annotation data from the scientific literature into these databases. Here, we introduce
MotifAdjuster , a tool that helps to detect these errors, and we demonstrate its efficacy on public data sets. 相似文献
982.
Carsten Schleh Christian Mühlfeld Karin Pulskamp Andreas Schmiedl Matthias Nassimi Hans D Lauenstein Armin Braun Norbert Krug Veit J Erpenbeck Jens M Hohlfeld 《Respiratory research》2009,10(1):90
Background
Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO2) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO2 effects on surfactant ultrastructure were visualized.Methods
A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 μg/ml) of TiO2 NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope.Results
TiO2 NSP, but not MSP, induced a surfactant dysfunction. For TiO2 NSP, adsorption surface tension (γads) increased in a dose-dependent manner from 28.2 ± 2.3 mN/m to 33.2 ± 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (γmin) slightly increased from 4.8 ± 0.5 mN/m up to 8.4 ± 1.3 mN/m (p < 0.01) at high TiO2 NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both γads (63.6 ± 0.4 mN/m) and γmin (21.1 ± 0.4 mN/m). Interestingly, TiO2 NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae.Conclusion
TiO2 nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung. 相似文献983.
Louise M Sørensen Rene Lametsch Mikael R Andersen Per V Nielsen Jens C Frisvad 《BMC microbiology》2009,9(1):255-20
Background
Aspergillus niger is a filamentous fungus found in the environment, on foods and feeds and is used as host for production of organic acids, enzymes and proteins. The mycotoxin fumonisin B2 was recently found to be produced by A. niger and hence very little is known about production and regulation of this metabolite. Proteome analysis was used with the purpose to reveal how fumonisin B2 production by A. niger is influenced by starch and lactate in the medium. 相似文献984.
Konstantin Schneider Jens Olaf Krömer Christoph Wittmann Isabel Alves-Rodrigues Andreas Meyerhans Juana Diez Elmar Heinzle 《Microbial cell factories》2009,8(1):12-14
Background
The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the replication of some positive-strand viruses and therefore are potential targets for new antiviral drugs. To prioritize host targets for antiviral drug screening a comparative metabolome analysis in Saccharomyces cerevisiae reference strain BY4742 Matα his3Δ1 leu2Δ0 lys2Δ0 ura3Δ0 and deletion strains pat1Δ, lsm1Δ and dhh1Δ was performed. 相似文献985.
Lake-Ee Quek Christoph Wittmann Lars K Nielsen Jens O Krömer 《Microbial cell factories》2009,8(1):25-15
Background
The quantitative analysis of metabolic fluxes, i.e., in vivo activities of intracellular enzymes and pathways, provides key information on biological systems in systems biology and metabolic engineering. It is based on a comprehensive approach combining (i) tracer cultivation on 13C substrates, (ii) 13C labelling analysis by mass spectrometry and (iii) mathematical modelling for experimental design, data processing, flux calculation and statistics. Whereas the cultivation and the analytical part is fairly advanced, a lack of appropriate modelling software solutions for all modelling aspects in flux studies is limiting the application of metabolic flux analysis. 相似文献986.
Julia Freise Iris Bernau Sabine Meier Henning Zeidler Jens G Kuipers 《Arthritis research & therapy》2009,11(6):R175-10
Introduction
Polymerase chain reaction (PCR) and ligase chain reaction (LCR) are used in research for detection of Chlamydia trachomatis (C. tr.) in synovial fluid (SF). However there is no standardized system for diagnostic use in clinical practice, therefore this study aimed at determining the molecular biology method best suited to detect C. tr. from SF. 相似文献987.
DNA electrotransfer to muscle tissue yields long-term, high levels of gene expression; showing great promise for future gene
therapy. We want to characterize the novel far-red fluorescent protein Katushka as a marker for gene expression using time
domain fluorescence in vivo imaging. Highly efficient transgenic expression was observed after DNA electrotransfer with 100-fold
increase in fluorescent intensity. The fluorescent signal peaked 1 week after transfection and returned to background level
within 4 weeks. Katushka expression was not as stable as GFP expression, which was detectable for 8 weeks. Depth and 3D analysis
proved that the expression was located in the target muscle. In vivo bio-imaging using the novel Katushka fluorescent protein
enables excellent evaluation of the transfection efficacy, and spatial distribution, but lacks long-term stability. 相似文献
988.
Lucas P Carlstrom Jackie K Jens Marley E Dobyns Merry Passage Patricia I Dickson N Matthew Ellinwood 《Comparative medicine》2009,59(4):378-382
Issues of cost and genetics can result in inbreeding of canine genetic disease colonies. Beagles often are used to maintain such colonies, providing stock for outcrosses. Factor VII (FVII) deficiency is a hemostatic disorder found at increased frequency in beagles and has been characterized at the DNA level. Deficiency of FVII presents obstacles in colonies founded with beagles. An initial finding of a FVII-deficient pup from a longstanding colony prompted us to evaluate FVII deficiency fully in this colony. Current and archival records and tissues were used to reconstruct the colony pedigree, assess the contribution from beagles, and test samples to document the source and frequency of the mutant FVII allele. As part of this study we developed a PCR-based diagnostic assay that was simpler than what was previously available. Pedigree analysis revealed a founder effect implicating beagles that led to high frequency (55%) of the mutant allele. In addition, affected animals were identified. The complete picture of the clinical effect within the colony remains unclear, but unusual neonatal presentations, including hemoabdomen, have occurred in pups affected with FVII deficiency. Use of a PCR-based diagnostic assay to screen all potential beagle breeding stock will prevent similar occurrences of FVII deficiency in future canine research colonies.Abbreviations: FVII, factor VII; MPS I, mucopolysaccharidosis I; PT, prothrombin timeThe importance of developing clinically relevant large animal models for human genetic diseases is becoming increasingly evident.4 For example, preclinical assessments of gene transfer experiments require large long-lived animal models physiologically and genetically comparable to humans. Canine models are ideal because their genome has been sequenced, they are large and long-lived, and because more than 60% of inherited diseases of dogs are known to be homologs of human diseases.4The maintenance of genetic diseases in research colonies results, for all practical purposes, in a founder effect by which allelic frequencies in a research colony may be skewed upward from those in the general population, due to founding of the colony by a limited number of animals. This founder effect is due to insufficient genetic outcrosses, resulting from economic constraints and considerations such as the inbreeding needed with a recessive condition. Practically speaking, colony founders may inevitably be incompletely characterized at the genetic level, potentially leading to increased prevalence of an additional genetic disease. When available, practical screening tests (clotting times, cardiac evaluation, and so on) or breed-specific genetic tests should be conducted to reduce additional genetic diseases within a research colony.The occurrence of additional genetic diseases in research colonies can limit or confound the primary research objective and affect the number of research animals used and their health and welfare. Inherited factor VII (FVII) deficiency in beagles is such a condition.8 Although largely an asymptomatic defect, this autosomal recessive hemostatic disorder, can lead to excessive bleeding after surgery or trauma, hematoma formation, body cavity bleeding, and persistent uterine and vaginal hemorrhage.23 Factor VII deficiency also occurs in Alaskan malamutes,14 mixed breeds,13 and Alaskan klee kai dogs.11 Clinical symptoms in canines can be reduced by transfusions with fresh plasma or blood, or administration of recombinant activated human FVII.9,17 However, treatments are only a temporary solution, because the half-life of FVII protein is only 3 to 4 h and, in canines, treatment with human proteins raises concern about antibody responses to those proteins, thus potentially limiting further therapy. The FVII mutation initially described in beagles (referred to henceforth as the ‘beagle mutation’ in full recognition of its occurrence in additional breeds) is well described.1 Furthermore the beagle mutation has been documented to cause the FVII deficiency seen in the Alaskan klee kai,11 Airedale terrier, giant schnauzer, and Scottish deerhound.22 The published assay is a restriction digest to test beagles for the causative transitional missense mutation of a guanine-to-adenine located in exon 5 (leading to the G96E mutant protein).1 However, because the assay relies on an enzyme with multiple sites in the resultant amplicon, interpretation of results can be problematic, potentially requiring direct DNA sequencing for confirmation of the genotype.Herein we present data from a long-standing canine research breeding colony for mucopolysaccharidosis type I (MPS I) which indicate that FVII deficiency should be a primary concern when developing research colonies by using beagle breeding stock. We suspected factor VII deficiency in this colony after an episode of hemoabdomen in a neonate, which was noted shortly after the colony was transferred to a different institution. Using an improved PCR-based diagnostic assay for the beagle FVII mutation, we have documented the history of this mutant allele within the colony in detail and have identified the presence of this allele in other canine colonies. 相似文献
989.
Nicole Philippi Dorothee Walter Rebekka Schlatter Karine Ferreira Michael Ederer Oliver Sawodny Jens Timmer Christoph Borner Thomas Dandekar 《BMC systems biology》2009,3(1):97-11
Background
The decision pro- or contra apoptosis is complex, involves a number of different inputs, and is central for the homeostasis of an individual cell as well as for the maintenance and regeneration of the complete organism. 相似文献990.
Munir A. Al-Zeer Hesham M. Al-Younes Peter R. Braun Jens Zerrahn Thomas F. Meyer 《PloS one》2009,4(2)
Chlamydial infection of the host cell induces Gamma interferon (IFNγ), a central immunoprotector for humans and mice. The primary defense against Chlamydia infection in the mouse involves the IFNγ-inducible family of IRG proteins; however, the precise mechanisms mediating the pathogen''s elimination are unknown. In this study, we identify Irga6 as an important resistance factor against C. trachomatis, but not C. muridarum, infection in IFNγ-stimulated mouse embryonic fibroblasts (MEFs). We show that Irga6, Irgd, Irgm2 and Irgm3 accumulate at bacterial inclusions in MEFs upon stimulation with IFNγ, whereas Irgb6 colocalized in the presence or absence of the cytokine. This accumulation triggers a rerouting of bacterial inclusions to autophagosomes that subsequently fuse to lysosomes for elimination. Autophagy-deficient Atg5−/− MEFs and lysosomal acidification impaired cells surrender to infection. Irgm2, Irgm3 and Irgd still localize to inclusions in IFNγ-induced Atg5−/− cells, but Irga6 localization is disrupted indicating its pivotal role in pathogen resistance. Irga6-deficient (Irga6−/−) MEFs, in which chlamydial growth is enhanced, do not respond to IFNγ even though Irgb6, Irgd, Irgm2 and Irgm3 still localize to inclusions. Taken together, we identify Irga6 as a necessary factor in conferring host resistance by remodelling a classically nonfusogenic intracellular pathogen to stimulate fusion with autophagosomes, thereby rerouting the intruder to the lysosomal compartment for destruction. 相似文献