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221.
Sudeep Chenna Narendra Jaya Prakash Chalise Mattias Magnusson Srinivas Uppugunduri 《PloS one》2015,10(10)
Objective
Uridine has earlier been show to down modulate inflammation in models of lung inflammation. The aim of this study was to evaluate the anti-inflammatory effect of uridine in arthritis.Methods
Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice pre-immunized with mBSA. Uridine was either administered locally by direct injection into the knee joint or systemically. Systemic treatment included repeated injections or implantation of a pellet continuously releasing uridine during the entire experimental procedure. Anti-mBSA specific immune responses were determined by ELISA and cell proliferation and serum cytokine levels were determined by Luminex. Immunohistochemistry was used to identify cells, study expression of cytokines and adhesion molecules in the joint.Results
Local administration of 25–100 mg/kg uridine at the time of arthritis onset clearly prevented development of joint inflammation. In contrast, systemic administration of uridine (max 1.5 mg uridine per day) did not prevent development of arthritis. Protection against arthritis by local administration of uridine did not affect the anti-mBSA specific immune response and did not prevent the rise in serum levels of pro-inflammatory cytokines associated with the triggering of arthritis. In contrast, local uridine treatment efficiently inhibited synovial expression of ICAM-1 and CD18, local cytokine production and recruitment of leukocytes to the synovium.Conclusion
Local, but not systemic administration of uridine efficiently prevented development of antigen-induced arthritis. The protective effect did not involve alteration of systemic immunity to mBSA but clearly involved inhibition of synovial expression of adhesion molecules, decreased TNF and IL-6 production and prevention of leukocyte extravasation. Further, uridine is a small, inexpensive molecule and may thus be a new therapeutic option to treat joint inflammation in RA. 相似文献222.
Dimitrios Konstantinidis Filipa Pereira EvaMaria Geissen Kristina Grkovska Eleni Kafkia Paula Jouhten Yongkyu Kim Saravanan Devendran Michael Zimmermann Kiran Raosaheb Patil 《Molecular systems biology》2021,17(8)
Adaptive laboratory evolution has proven highly effective for obtaining microorganisms with enhanced capabilities. Yet, this method is inherently restricted to the traits that are positively linked to cell fitness, such as nutrient utilization. Here, we introduce coevolution of obligatory mutualistic communities for improving secretion of fitness‐costly metabolites through natural selection. In this strategy, metabolic cross‐feeding connects secretion of the target metabolite, despite its cost to the secretor, to the survival and proliferation of the entire community. We thus co‐evolved wild‐type lactic acid bacteria and engineered auxotrophic Saccharomyces cerevisiae in a synthetic growth medium leading to bacterial isolates with enhanced secretion of two B‐group vitamins, viz., riboflavin and folate. The increased production was specific to the targeted vitamin, and evident also in milk, a more complex nutrient environment that naturally contains vitamins. Genomic, proteomic and metabolomic analyses of the evolved lactic acid bacteria, in combination with flux balance analysis, showed altered metabolic regulation towards increased supply of the vitamin precursors. Together, our findings demonstrate how microbial metabolism adapts to mutualistic lifestyle through enhanced metabolite exchange. 相似文献
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225.
Dent A. Earl Kristina D. Louie Carolyne Bardeleben Camm C. Swift David K. Jacobs 《Conservation Genetics》2010,11(1):103-114
The federally endangered tidewater goby, Eucyclogobius newberryi, is the most locally differentiated vertebrate with marine dispersal on the California Coast. It inhabits seasonally closed
estuaries along the California coast; a habitat heavily impacted by anthropogenic filling and artificial opening, and exhibits
varied metapopulation behavior as a consequence of hydrologic variation and anthropogenic impact. We describe 19 taxon-specific
microsatellite loci, and assess genetic variation across the taxon range relative to genetic subdivision. A highly divergent
southern clade, with reduced genetic variation, now confined to Northern San Diego County, appears to merit status as a separate
species. The mid-coast is subdivided into regional groups with overall similarity to, and minor differences from previous
mitochondrial sequence based clades. The northernmost region, although locally differentiated, forms a star phylogeny with
limited geographic structure which we attribute to dispersal during Pleistocene/Holocene sea-level rise followed by increasing
isolation during the Holocene. Bottleneck/founder events are evident in some habitats thought to have experienced (anthropogenic)
extirpation. Further work with more, and larger, samples will be required to assess local and regional differences. Analytical
methods employed include Analysis of Molecular Variance (AMOVA), Neighbor-Joining, Bayesian/STRUCTURE analysis and Principle
Components Analysis (PCA). 相似文献
226.
Alexander Weng Kristina Jenett-Siems Peter Schmieder Diana Bachran Christopher Bachran Cornelia Görick Mayank Thakur Hendrik Fuchs Matthias F. Melzig 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(7-8):713-718
Saponinum album (Merck), which is a crude mixture of saponins from Gypsophila paniculata L., was shown to improve the anti cancer therapy when used in vivo in combination with saporin-based targeted toxins. Unfortunately saponinum album cannot be used for further development since Merck has ceased its production in the 1990s. As pure saponins are mandatory for use in medical purposes we developed a convenient method for saponin isolation directly from the roots of Gypsophila paniculata L. The developed method is rapid, cheap and scaling up is also possible. By combining dialysis and HPLC three saponins were isolated in a one-step procedure. Chemical structures of the purified saponins were characterized by extensive one and two-dimensional NMR-spectroscopy and by using ESI-TOF-MS. The biological activities of the purified saponins were also investigated. The method presented herein enabled a rapid and cheap isolation of saponins for tumour therapy. 相似文献
227.
Karin?Born Anja?Manns Kristina?Dzeyk Sabine?Lutz-Wahl Daniel?Gau Lutz?FischerEmail author 《Biotechnology letters》2010,32(2):249-253
Ultrasonic resonator technology (URT) was compared with the well established UV–Vis/ninhydrin assay to estimate protease activities
in defined buffer systems. Hydrolysis of casein was measured using subtilisin, trypsin, halophilic protease from Haloferax mediterranei and Bacillus lentus alkaline protease. Sensitivity, reproducibility, working range as well as the limit of detection and the limit of quantification
were comparable for both methods. Salt concentrations (0.5 M NaCl) interfered with the URT method. The quantification of protease
activity by URT was possible when the product concentration measured by the UV–Vis/ninhydrin assay was correlated to the corresponding
ultrasonic velocity signals. 相似文献
228.
Helmut P Sandeck Oluf D Røe Kristina Kjærheim Helena Willén Erik Larsson 《Diagnostic pathology》2010,5(1):1-15
Background
In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.Methods
Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.Results
49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM. With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia. In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers. The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3). 46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.Conclusions
In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment. 相似文献229.
Cyclotides are disulfide-rich plant proteins that are exceptional in their cyclic structure; their N and C termini are joined by a peptide bond, forming a continuous circular backbone, which is reinforced by three interlocked disulfide bonds. Cyclotides have been found mainly in the coffee (Rubiaceae) and violet (Violaceae) plant families. Within the Violaceae, cyclotides seem to be widely distributed, but the cyclotide complements of the vast majority of Violaceae species have not yet been explored. This study provides insight into cyclotide occurrence, diversity and biosynthesis in the Violaceae, by identifying mature cyclotide proteins, their precursors and enzymes putatively involved in their biosynthesis in the tribe Rinoreeae and the genus Gloeospermum. Twelve cyclotides from two Panamanian species, Gloeospermum pauciflorum Hekking and Gloeospermum blakeanum (Standl.) Hekking (designated Glopa A-E and Globa A-G, respectively) were characterised through cDNA screening and protein isolation. Screening of cDNA for the oxidative folding enzymes protein-disulfide isomerase (PDI) and thioredoxin (TRX) resulted in positive hits in both species. These enzymes have demonstrated roles in oxidative folding of cyclotides in Rubiaceae, and results presented here indicate that Violaceae plants have evolved similar mechanisms of cyclotide biosynthesis. We also describe PDI and TRX sequences from a third cyclotide-expressing Violaceae species, Viola biflora L., which further support this hypothesis. 相似文献
230.
Cecilia Ferndahl Nicklas Bonander Christel Logez Renaud Wagner Lena Gustafsson Christer Larsson Kristina Hedfalk Richard AJ Darby Roslyn M Bill 《Microbial cell factories》2010,9(1):47