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排序方式: 共有405条查询结果,搜索用时 15 毫秒
71.
Wang XX Jiang T Shen Y Santamaria H Solis N Arbeeny C Levi M 《American journal of physiology. Renal physiology》2011,300(3):F801-F810
Diet-induced obesity (DIO) and insulin resistance in mice are associated with proteinuria, renal mesangial expansion, accumulation of extracellular matrix proteins, and activation of oxidative stress, proinflammatory cytokines, profibrotic growth factors, and the sterol regulatory element binding proteins, SREBP-1 and SREBP-2, that mediate increases in fatty acid and cholesterol synthesis. The purpose of the present study was to determine whether treatment of DIO mice with the vitamin D receptor (VDR) agonist doxercalciferol (1α-hydroxyvitamin D2) prevents renal disease. Our results indicate that treatment of DIO mice with the VDR agonist decreases proteinuria, podocyte injury, mesangial expansion, and extracellular matrix protein accumulation. The VDR agonist also decreases macrophage infiltration, oxidative stress, proinflammatory cytokines, and profibrotic growth factors. Furthermore, the VDR agonist also prevents the activation of the renin-angiotensin-aldosterone system including the angiotensin II type 1 receptor and the mineralocorticoid receptor. An additional novel finding of our study is that activation of VDR results in decreased accumulation of neutral lipids (triglycerides and cholesterol) and expression of adipophilin in the kidney by decreasing SREBP-1 and SREBP-2 expression and target enzymes that mediate fatty acid and cholesterol synthesis and increasing expression of the farnesoid X receptor. This study therefore demonstrates multiple novel effects of VDR activation in the kidney which prevent renal manifestations of DIO in the kidney. 相似文献
72.
Chee J Angstetra E Mariana L Graham KL Carrington EM Bluethmann H Santamaria P Allison J Kay TW Krishnamurthy B Thomas HE 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(4):1702-1712
TNF has been implicated in the pathogenesis of type 1 diabetes. When administered early in life, TNF accelerates and increases diabetes in NOD mice. However, when administered late, TNF decreases diabetes incidence and delays onset. TNFR1-deficient NOD mice were fully protected from diabetes and only showed mild peri-insulitis. To further dissect how TNFR1 deficiency affects type 1 diabetes, these mice were crossed to β cell-specific, highly diabetogenic TCR transgenic I-A(g7)-restricted NOD4.1 mice and Kd-restricted NOD8.3 mice. TNFR1-deficient NOD4.1 and NOD8.3 mice were protected from diabetes and had significantly less insulitis compared with wild type NOD4.1 and NOD8.3 controls. Diabetic NOD4.1 mice rejected TNFR1-deficient islet grafts as efficiently as control islets, confirming that TNFR1 signaling is not directly required for β cell destruction. Flow cytometric analysis showed a significant increase in the number of CD4(+)CD25(+)Foxp3(+) T regulatory cells in TNFR1-deficient mice. TNFR1-deficient T regulatory cells were functionally better at suppressing effector cells than were wild type T regulatory cells both in vitro and in vivo. This study suggests that blocking TNF signaling may be beneficial in increasing the function of T regulatory cells and suppression of type 1 diabetes. 相似文献
73.
Magnetospirillum magnetotacticum are magnetotactic bacteria that form a single chain of magnetite magnetosomes within its cytoplasm. Here, we studied the
ultrastructure of M. magnetotacticum by freeze-fracture and deep-etching to understand the spatial correlation between the
magnetosome chain and the cell envelope and its possible implications for magnetotaxis. Magnetosomes were found mainly near
the cell envelope, forming chains that were closely associated with the granular cytoplasmic material. The membrane surrounding
the magnetosomes could be visualized in deep-etching preparations. Thin connections between magnetosome chains and the cell
envelope were observed in deep-etching images. These results strengthen the hypothesis for the existence of structures that
transfer the torque from the magnetosome chains to the whole cell during the orientation of magnetotactic bacteria to a magnetic
field lines. 相似文献
74.
Culture‐independent characterization of a novel magnetotactic member affiliated to the Beta class of the Proteobacteria phylum from an acidic lagoon 下载免费PDF全文
Fernanda Abreu Pedro Leão Gabriele Vargas Jefferson Cypriano Viviane Figueiredo Alex Enrich‐Prast Dennis A. Bazylinski Ulysses Lins 《Environmental microbiology》2018,20(7):2615-2624
Magnetotactic bacteria (MTB) comprise a group of motile microorganisms common in most mesothermal aquatic habitats with pH values around neutrality. However, during the last two decades, a number of MTB from extreme environments have been characterized including: cultured alkaliphilic strains belonging to the Deltaproteobacteria class of the Proteobacteria phylum; uncultured moderately thermophilic strains belonging to the Nitrospirae phylum; cultured and uncultured moderately halophilic or strongly halotolerant bacteria affiliated with the Deltaproteobacteria and Gammaproteobacteria classes and an uncultured psychrophilic species belonging to the Alphaproteobacteria class. Here, we used culture‐independent techniques to characterize MTB from an acidic freshwater lagoon in Brazil (pH ~ 4.4). MTB morphotypes found in this acidic lagoon included cocci, rods, spirilla and vibrioid cells. Magnetite (Fe3O4) was the only mineral identified in magnetosomes of these MTB while magnetite magnetosome crystal morphologies within the different MTB cells included cuboctahedral (present in spirilla), elongated prismatic (present in cocci and vibrios) and bullet‐shaped (present in rod‐shaped cells). Intracellular pH measurements using fluorescent dyes showed that the cytoplasmic pH was close to neutral in most MTB cells and acidic in some intracellular granules. Based on 16S rRNA gene phylogenetic analyses, some of the retrieved gene sequences belonged to the genus Herbaspirillum within the Betaproteobacteria class of the Proteobacteria phylum. Fluorescent in situ hybridization using a Herbaspirillum‐specific probe hybridized with vibrioid MTB in magnetically‐enriched samples. Transmission electron microscopy of the Herbaspirillum‐like MTB revealed the presence of many intracellular granules and a single chain of elongated prismatic magnetite magnetosomes. Diverse populations of MTB have not seemed to have been described in detail in an acid environment. In addition, this is the first report of an MTB phylogenetically affiliated with Betaproteobacteria class. 相似文献
75.
Alvaro C. Ucero Alberto Benito-Martin Isabel Fuentes-Calvo Beatriz Santamaria Julia Blanco Jose M. Lopez-Novoa Marta Ruiz-Ortega Jesus Egido Linda C. Burkly Carlos Martinez-Salgado Alberto Ortiz 《生物化学与生物物理学报:疾病的分子基础》2013,1832(10):1744-1755
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) regulates apoptosis, proliferation and inflammation in renal epithelial cells and plays a role in acute kidney injury. However, there is little information on the chronic effects of TWEAK. We hypothesized that TWEAK may influence renal fibrosis and regulate kidney fibroblast biology, in part, through Ras pathway.We studied a chronic model of experimental unilateral ureteral obstruction in wild type and TWEAK deficient mice, and a murine model of systemic TWEAK overexpression. TWEAK actions were also explored in cultured renal and embryonic fibroblasts.TWEAK and TWEAK receptor expression was increased in the obstructed kidneys. The absence of TWEAK decreased early kidney tubular damage, inflammatory infiltrates and myofibroblast number. TWEAK deficient mice had decreased renal fibrosis 21 days after obstruction, as assessed by extracellular matrix staining. In mice without prior underlying kidney disease, systemic overexpression of TWEAK induced kidney inflammation and fibrosis. In cultured fibroblasts, TWEAK induced proliferation through activation of the Ras/ERK pathway. TWEAK also activated nuclear factor κB (NFκB)-dependent inflammatory chemokine production in murine renal fibroblasts.In conclusion, lack of TWEAK reduces renal fibrosis in a model of persistent kidney insult and overexpression of TWEAK led to renal fibrosis. TWEAK actions on renal fibroblasts may contribute to the in vivo observations, as TWEAK promotes inflammatory activity and proliferation in fibroblast cultures. 相似文献
76.
Scorza T Grubb K Cambos M Santamaria C Tshikudi Malu D Spithill TW 《International journal for parasitology》2008,38(7):819-827
A current goal of malaria vaccine research is the development of vaccines that will cross-protect against multiple strains of malaria. In the present study, the breadth of cross-reactivity induced by a 30K multivalent DNA vaccine has been evaluated in susceptible A/J mice (H-2a) against infection with the Plasmodium chabaudi adami DK strain and a virulent parasite subspecies, Plasmodium chabaudi chabaudi AS. Immunized A/J mice were significantly protected against infection with both P. c. adami DK (31–40% reduction in cumulative parasitemia) and P. c. chabaudi AS parasites, where a 30–39% reduction in cumulative parasitemia as well as enhanced survival was observed. The 30K vaccine-induced specific IFN-γ production by splenocytes in response to native antigens from both P. c. chabaudi AS and P. c. adami DK. Specific antibodies reacting with surface antigens expressed on P. c. adami DS and P. c. chabaudi AS infected red blood cells, and with opsonizing properties, were detected. These results suggest that multivalent vaccines encoding conserved antigens can feasibly induce immune cross-reactivity that span Plasmodium strains and subspecies and can protect hosts of distinct major histocompatibility complex haplotypes. 相似文献
77.
Andrew Pullin Geoff Frampton Rob Jongman Christian Kohl Barbara Livoreil Alexandra Lux György Pataki Gillian Petrokofsky Aranka Podhora Heli Saarikoski Luis Santamaria Stefan Schindler Isabel Sousa-Pinto Marie Vandewalle Heidi Wittmer 《Biodiversity and Conservation》2016,25(7):1285-1300
Responding to different questions generated by biodiversity and ecosystem services policy or management requires different forms of knowledge (e.g. scientific, experiential) and knowledge synthesis. Additionally, synthesis methods need to be appropriate to policy context (e.g. question types, budget, timeframe, output type, required scientific rigour). In this paper we present a range of different methods that could potentially be used to conduct a knowledge synthesis in response to questions arising from knowledge needs of decision makers on biodiversity and ecosystem services policy and management. Through a series of workshops attended by natural and social scientists and decision makers we compiled a range of question types, different policy contexts and potential methodological approaches to knowledge synthesis. Methods are derived from both natural and social sciences fields and reflect the range of question and study types that may be relevant for syntheses. Knowledge can be available either in qualitative or quantitative form and in some cases also mixed. All methods have their strengths and weaknesses and we discuss a sample of these to illustrate the need for diversity and importance of appropriate selection. To summarize this collection, we present a table that identifies potential methods matched to different combinations of question types and policy contexts, aimed at assisting teams undertaking knowledge syntheses to select appropriate methods. 相似文献
78.
Gudrun C. Hartmann Elena Santamaria Victor M. Fernández R. K. Thauer 《Journal of biological inorganic chemistry》1996,1(5):446-450
H2–forming N 5,N 10 –methylenetetrahydromethanopterin dehydrogenase is a novel type of hydrogenase that contains neither nickel nor iron-sulfur clusters. Evidence has been presented that the reaction mechanism catalyzed by the enzyme is very similar to that of the formation of carbocations and H2 from alkanes under superacidic conditions. We present here further results in support of this mechanism. It was found that the purified enzyme per se did not catalyze the conversion of para H2 to ortho H2, a reaction catalyzed by all other hydrogenases known to date. However, it catalyzed the conversion in the presence of the substrate N 5,N 10 –methenyltetrahydromethanopterin (CH≡H4MPT+), indicating that for heterolytic cleavage of H2 the enzyme-CH≡H4MPT+ complex is required. In D2O, the formation of HD and D2 from H2 rather than a para–ortho H2 conversion was observed, indicating that after heterolytic cleavage of H2 the dissociation of the proton from the enzyme-substrate complex is fast relative to the re-formation of free H2. 相似文献
79.
80.
Leimkuhler S Freuer A Araujo JA Rajagopalan KV Mendel RR 《The Journal of biological chemistry》2003,278(28):26127-26134
Biosynthesis of the molybdenum cofactor involves the initial formation of precursor Z, its subsequent conversion to molybdopterin (MPT) by MPT synthase, and attachment of molybdenum to the dithiolene moiety of MPT. The sulfur used for the formation of the dithiolene group of MPT exists in the form of a thiocarboxylate group at the C terminus of the smaller subunit of MPT synthase. Human MPT synthase contains the MOCS2A and MOCS2B proteins that display homology to the Escherichia coli proteins MoaD and MoaE, respectively. MOCS2A and MOCS2B were purified after heterologous expression in E. coli, and the separately purified subunits readily assemble into a functional MPT synthase tetramer. The rate of conversion of precursor Z to MPT by the human enzyme is slower than that of the eubacterial homologue. To obtain insights into the molecular mechanism leading to human molybdenum cofactor deficiency, site-specific mutations identified in patients showing symptoms of molybdenum cofactor deficiency were generated. Characterization of a V7F substitution in MOCS2A, identified in a patient with an unusual mild form of the disease, showed that the mutation weakens the interaction between MOCS2A and MOCS2B, whereas a MOCS2B-E168K mutation identified in a severely affected patient attenuates binding of precursor Z. 相似文献