排序方式： 共有33条查询结果，搜索用时 15 毫秒
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Asagiri M Hirai T Kunigami T Kamano S Gober HJ Okamoto K Nishikawa K Latz E Golenbock DT Aoki K Ohya K Imai Y Morishita Y Miyazono K Kato S Saftig P Takayanagi H 《Science (New York, N.Y.)》2008,319(5863):624-627
Cathepsin K was originally identified as an osteoclast-specific lysosomal protease, the inhibitor of which has been considered might have therapeutic potential. We show that inhibition of cathepsin K could potently suppress autoimmune inflammation of the joints as well as osteoclastic bone resorption in autoimmune arthritis. Furthermore, cathepsin K-/- mice were resistant to experimental autoimmune encephalomyelitis. Pharmacological inhibition or targeted disruption of cathepsin K resulted in defective Toll-like receptor 9 signaling in dendritic cells in response to unmethylated CpG DNA, which in turn led to attenuated induction of T helper 17 cells, without affecting the antigen-presenting ability of dendritic cells. These results suggest that cathepsin K plays an important role in the immune system and may serve as a valid therapeutic target in autoimmune diseases. 相似文献
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Olivieri A Achilli A Pala M Battaglia V Fornarino S Al-Zahery N Scozzari R Cruciani F Behar DM Dugoujon JM Coudray C Santachiara-Benerecetti AS Semino O Bandelt HJ Torroni A 《Science (New York, N.Y.)》2006,314(5806):1767-1770
Sequencing of 81 entire human mitochondrial DNAs (mtDNAs) belonging to haplogroups M1 and U6 reveals that these predominantly North African clades arose in southwestern Asia and moved together to Africa about 40,000 to 45,000 years ago. Their arrival temporally overlaps with the event(s) that led to the peopling of Europe by modern humans and was most likely the result of the same change in climate conditions that allowed humans to enter the Levant, opening the way to the colonization of both Europe and North Africa. Thus, the early Upper Palaeolithic population(s) carrying M1 and U6 did not return to Africa along the southern coastal route of the "out of Africa" exit, but from the Mediterranean area; and the North African Dabban and European Aurignacian industries derived from a common Levantine source. 相似文献
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Sara König Ulrich Weller Bibiana Betancur-Corredor Birgit Lang Thomas Reitz Martin Wiesmeier Ute Wollschläger Hans-Jörg Vogel 《European Journal of Soil Science》2023,74(5):e13411
The increasing demand for biomass for food, animal feed, fibre and bioenergy requires optimization of soil productivity, while at the same time, protecting other soil functions such as nutrient cycling and buffering, carbon storage, habitat for biological activity and water filter and storage. Therefore, one of the main challenges for sustainable agriculture is to produce high yields while maintaining all the other soil functions. Mechanistic simulation models are an essential tool to fully understand and predict the complex interactions between physical, biological and chemical processes of soils that generate those functions. We developed a soil model to simulate the impact of various agricultural management options and climate change on soil functions by integrating the relevant processes mechanistically and in a systemic way. As a special feature, we include the dynamics of soil structure induced by tillage and biological activity, which is especially relevant in arable soils. The model operates on a 1D soil profile consisting of a number of discrete layers with dynamic thickness. We demonstrate the model performance by simulating crop growth, root growth, nutrient and water uptake, nitrogen cycling, soil organic matter turnover, microbial activity, water distribution and soil structure dynamics in a long-term field experiment including different crops and different types and levels of fertilization. The model is able to capture essential features that are measured regularly including crop yield, soil organic carbon, and soil nitrogen. In this way, the plausibility of the implemented processes and their interactions is confirmed. Furthermore, we present the results of explorative simulations comparing scenarios with and without tillage events to analyse the effect of soil structure on soil functions. Since the model is process-based, we are confident that the model can also be used to predict quantities that have not been measured or to estimate the effect of management measures and climate states not yet been observed. The model thus has the potential to predict the site-specific impact of management decisions on soil functions, which is of great importance for the development of a sustainable agriculture that is currently also on the agenda of the ‘Green Deal’ at the European level. 相似文献
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Schuler D Chevalier HJ Merker M Morgenthal K Ravanat JL Sagelsdorff P Walter M Weber K McGregor D 《Journal of toxicologic pathology》2011,24(3):149-162
Inhalation of vanadium pentoxide clearly increases the incidence of
alveolar/bronchiolar neoplasms in male and female B6C3F1 mice at all
concentrations tested (1, 2 or 4 mg/m3), whereas responses in F344/N
rats was, at most, ambiguous. While vanadium pentoxide is mutagenic in
vitro and possibly in vivo in mice, this does not
explain the species or site specificity of the neoplastic response. A nose-only
inhalation study was conducted in female B6C3F1 mice (0, 0.25, 1 and
4 mg/m3, 6 h/day for 16 days) to explore histopathological,
biochemical (α-tocopherol, glutathione and F2-isoprostane) and genetic (comet
assays and 9 specific DNA-oxo-adducts) changes in the lungs. No treatment
related histopathology was observed at 0.25 mg/m3. At 1 and
4 mg/m3, exposure-dependent increases were observed in lung
weight, alveolar histiocytosis, sub-acute alveolitis and/or granulocytic
infiltration and a generally time-dependent increased cell proliferation rate of
histiocytes. Glutathione was slightly increased, whereas there were no
consistent changes in α-tocopherol or 8-isoprostane F2α. There was no evidence
for DNA strand breakage in lung or BAL cells, but there was an increase in
8-oxodGuo DNA lesions that could have been due to vanadium pentoxide induction
of the lesions or inhibition of repair of spontaneous lesions. Thus, earlier
reports of histopathological changes in the lungs after inhalation of vanadium
pentoxide were confirmed, but no evidence has yet emerged for a genotoxic mode
of action. Evidence is weak for oxidative stress playing any role in lung
carcinogenesis at the lowest effective concentrations of vanadium pentoxide. 相似文献
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The aim of this prospective study was to evaluate the prevalence of feline haemotropic mycoplasmas in Germany, to determine probable risk factors for these infections and to compare the diagnostic value of microscopic examination of blood smears to polymerase chain reaction (PCR). For the prevalence study, convenience samples (Ethylene diamine-tetraacetic acid (EDTA) blood) from 262 (64.5% male and 35.5% female) cats were included. A PCR for the detection of Mycoplasma haemofelis (MHF) and 'Candidatus Mycoplasma haemominutum' (CMH) as well as a feline leukaemia virus (FeLV)/feline immunodeficiency virus (FIV) enzyme-linked immunoassay was performed. Blood smears from 224 cats were examined and the sensitivity and specificity of the microscopic diagnosis were determined. The prevalence of CMH, MHF, and CMH/MHF co-infection was 22.5%, 4.5%, and 0.8%, respectively. CMH was significantly associated with male gender (P=0.047), older age (P=0.0015) and both FeLV (P=0.002) and FIV infections (P<0.0001). However, there was no association between the presence of anaemia and CMH/MHF infection. The respective sensitivity and specificity of the microscopic diagnosis were 10.3% and 87.1% for a CMH infection and 0.0% and 98.0% for MHF infection. 相似文献
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Lauer B Ottleben I Jacobsen HJ Reinard T 《Journal of agricultural and food chemistry》2005,53(4):899-904
The selection of synthetic antibody fragments from large phage libraries has become a common method for the generation of specific antibodies. The technique is particularly valuable when antibodies against small, non-immunogenic molecules (haptens) or highly toxic substances have to be produced. In addition, haptens are usually coupled to protein carriers, bearing the risk that the free hapten is not detectable. Here, a single variable chain antibody (scFv) against the highly toxic mycotoxin fumonisin B1 has been produced. The hapten was coupled via a linker to biotin. Using this conjugate and a naive scFv library, it was possible to circumvent both the necessity of immunization and the risk of a disguised hapten. The scFv obtained after three panning rounds was found to bind specifically to both free fumonisin B1 and fumonisin-biotin conjugate. Also fumonisin B2 was bound by the scFv. Modeling of both scFv and fumonisin B1 molecule revealed a good fitting of structures. The antibody obtained can potentially be used for developing a rapid and affordable immunoassay for detection of food contamination and can be applied in immunoaffinity chromatography, usually carried out prior to HPLC analysis of mycotoxin-contaminated food and feed. 相似文献