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1.
Isolation of cationic peptides from rat polymorphonuclear leukocyte granule contents using fast protein liquid chromatography 总被引:4,自引:0,他引:4
Separation of extracted rat polymorphonuclear leukocyte (PMN) granule contents using fast protein liquid chromatography yielded four major protein fractions. These fractions consisted of myeloperoxidase (peak A), neutral protease (peak B), lysozyme (peak C), and low molecular weight, cationic peptides (peak D). This study represents the first noted purification of the cationic peptides of rat PMN granules. 相似文献
2.
Weickert MO Loeffelholz CV Roden M Chandramouli V Brehm A Nowotny P Osterhoff MA Isken F Spranger J Landau BR Pfeiffer AF Möhlig M 《American journal of physiology. Endocrinology and metabolism》2007,293(4):E1078-E1084
Liver fatty acid-binding protein (L-FABP) is a highly conserved key factor in lipid metabolism. Amino acid replacements in L-FABP might alter its function and thereby affect glucose metabolism in lipid-exposed subjects, as indicated by studies in L-FABP knockout mice. Amino acid replacements in L-FABP were investigated in a cohort of 1,453 Caucasian subjects. Endogenous glucose production (EGP), gluconeogenesis, and glycogenolysis were measured in healthy carriers of the only common Thr(94)-to-Ala amino acid replacement (Ala/Ala(94)) vs. age-, sex-, and BMI-matched wild-type (Thr/Thr(94)) controls at baseline and after 320-min lipid/heparin-somatostatin-insulin-glucagon clamps (n = 18). Whole body glucose disposal was further investigated (subset; n = 13) using euglycemic-hyperinsulinemic clamps without and with lipid/heparin infusion. In the entire cohort, the only common Ala/Ala(94) mutation was significantly associated with reduced body weight, which is in agreement with a previous report. In lipid-exposed, individually matched subjects there was a genotype vs. lipid-treatment interaction for EGP (P = 0.009) driven mainly by reduced glycogenolysis in Ala/Ala(94) carriers (0.46 +/- 0.05 vs. 0.59 +/- 0.05 mgxkg(-1)xmin(-1), P = 0.013). The lipid-induced elevation of plasma glucose levels was smaller in Ala/Ala(94) carriers compared with wild types (P < 0.0001). Whole body glucose disposal was not different between lipid-exposed L-FABP genotypes. In summary, the Ala/Ala(94)-mutation contributed significantly to reduced glycogenolysis and less severe hyperglycemia in lipid-exposed humans and was further associated with reduced body weight in a large cohort. Data clearly show that investigation of L-FABP phenotypes in the basal overnight-fasted state yielded incomplete information, and a challenge test was essential to detect phenotypical differences in glucose metabolism between L-FABP genotypes. 相似文献
3.
Savidge TC Urvil P Oezguen N Ali K Choudhury A Acharya V Pinchuk I Torres AG English RD Wiktorowicz JE Loeffelholz M Kumar R Shi L Nie W Braun W Herman B Hausladen A Feng H Stamler JS Pothoulakis C 《Nature medicine》2011,17(9):1136-1141
The global prevalence of severe Clostridium difficile infection highlights the profound clinical significance of clostridial glucosylating toxins. Virulence is dependent on the autoactivation of a toxin cysteine protease, which is promoted by the allosteric cofactor inositol hexakisphosphate (InsP(6)). Host mechanisms that protect against such exotoxins are poorly understood. It is increasingly appreciated that the pleiotropic functions attributed to nitric oxide (NO), including host immunity, are in large part mediated by S-nitrosylation of proteins. Here we show that C. difficile toxins are S-nitrosylated by the infected host and that S-nitrosylation attenuates virulence by inhibiting toxin self-cleavage and cell entry. Notably, InsP(6)- and inositol pyrophosphate (InsP(7))-induced conformational changes in the toxin enabled host S-nitrosothiols to transnitrosylate the toxin catalytic cysteine, which forms part of a structurally conserved nitrosylation motif. Moreover, treatment with exogenous InsP(6) enhanced the therapeutic actions of oral S-nitrosothiols in mouse models of C. difficile infection. Allostery in bacterial proteins has thus been successfully exploited in the evolutionary development of nitrosothiol-based innate immunity and may provide an avenue to new therapeutic approaches. 相似文献
4.
Hattersley JG Möhlig M Roden M Arafat AM Loeffelholz CV Nowotny P Machann J Hierholzer J Osterhoff M Khan M Pfeiffer AF Weickert MO 《PloS one》2012,7(6):e39029
We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6 ± 1.0 years, BMI 31.5 ± 0.4 kg/m(2); 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6-6(2)H(2)] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39-56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r(2) = 27-32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations. 相似文献
5.
The warm-season perennial switchgrass (Panicum virgatum) is a candidate bioenergy crop. To be successful, switchgrass production must be maintained on low-quality landscapes with minimal inputs while facing future climates that are expected to be more extreme and more variable. We propose that antecedent rainfall constrains how plants respond to drought, as well as subsequently recover from drought. To test this idea, we examined how six switchgrass genotypes responded to a 1-year severe drought and then recovered under normal rainfall in the following year. These plants had previously grown for 3 years under a range of dry to wet rainfall levels in a shallow-soil common garden with no fertilizer. Plants previously exposed to drought produced less biomass, and basal area after the severe drought was relieved compared to previously well-watered plants. In addition, there were legacy effects caused by plant size: plants that were larger pre-drought were more likely to survive the severe drought, and plants that were larger during the severe drought recovered more biomass, basal area, and tillers post-drought. Although genotypes differed somewhat in their responses, the size constraint was consistent across genotypes. These findings suggest that we can establish more drought-resilient switchgrass stands by, for example, planning for initial irrigation or planting during a wet year to allow plants to grow larger prior to experiencing drought. Additional studies are needed to understand whether these rainfall and size legacies persist or are transient. 相似文献
6.
The successful transfer of the resistance plasmid RP1 into the Gram-negative bacterium Acinetobacter calcoaceticus resulted in increased resistance of this microorganism to the antibiotics kanamycin and tetracycline. Microorganisms harboring the RP1 plasmid showed altered fatty acid composition in the lipopolysaccharide fraction and increased outer membrane permeability compared to organisms without the plasmid. Thermotropic gel to liquid crystal lipid phase changes were detected in both inner and outer membranes and purified lipopolysaccharide by Fourier transform infrared spectroscopy. The phase transition temperatures observed in the outer membranes and isolated lipopolysaccharide of the plasmid-containing cells were significantly higher than those of the plasmid-free organisms, while little difference was observed for the inner membranes. The plasmid-induced decrease in outer membrane fluidity may play a mediating role in the mechanisms of antibiotic resistance and susceptibility to host immune cells in Gram-negative microorganisms. 相似文献
7.
Sami J Savio Lara CV Harrison Tiina Luukkaala Tomi Heinonen Prasun Dastidar Seppo Soimakallio Hannu J Eskola 《Biomedical engineering online》2010,9(1):60
Background
The accuracy of texture analysis in clinical evaluation of magnetic resonance images depends considerably on imaging arrangements and various image quality parameters. In this paper, we study the effect of slice thickness on brain tissue texture analysis using a statistical approach and classification of T1-weighted images of clinically confirmed multiple sclerosis patients. 相似文献8.
José Rodrigues Coura Pedro Albajar Vi?as Angela CV Junqueira 《Memórias do Instituto Oswaldo Cruz》2014,109(7):856-862
Chagas disease is maintained in nature through the interchange of three cycles: the
wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has
existed for millions of years maintained between triatomines and wild mammals. Human
infection was only detected in mummies from 4,000-9,000 years ago, before the
discovery of the disease by Carlos Chagas in 1909. With the beginning of
deforestation in the Americas, two-three centuries ago for the expansion of
agriculture and livestock rearing, wild mammals, which had been the food source for
triatomines, were removed and new food sources started to appear in peridomestic
areas: chicken coops, corrals and pigsties. Some accidental human cases could also
have occurred prior to the triatomines in peridomestic areas. Thus, triatomines
progressively penetrated households and formed the domestic cycle of Chagas disease.
A new epidemiological, economic and social problem has been created through the
globalisation of Chagas disease, due to legal and illegal migration of individuals
infected by Trypanosoma cruzi or presenting Chagas disease in its
varied clinical forms, from endemic countries in Latin America to non-endemic
countries in North America, Europe, Asia and Oceania, particularly to the United
States of America and Spain. The main objective of the present paper was to present a
general view of the interchanges between the wild, peridomestic and domestic cycles
of the disease, the development of T. cruzi among triatomine, their
domiciliation and control initiatives, the characteristics of the disease in
countries in the Americas and the problem of migration to non-endemic countries. 相似文献
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10.
Olga Pivovarova Christian von Loeffelholz Iryna Ilkavets Carsten Sticht Sergei Zhuk Veronica Murahovschi Sonja Lukowski Stephanie D?cke Jennifer Kriebel Tonia de las Heras Gala Anna Malashicheva Anna Kostareva Johan F Lock Martin Stockmann Harald Grallert Norbert Gretz Steven Dooley Andreas FH Pfeiffer Natalia Rudovich 《Cell cycle (Georgetown, Tex.)》2015,14(14):2293-2300