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961.
962.
Michael S. Visser Kevin D. Freeman-Cook Steven J. Brickner Katherine E. Brighty Phuong T. Le Sarah K. Wade Rhonda Monahan Gary J. Martinelli Kyle T. Blair Dianna E. Moore 《Bioorganic & medicinal chemistry letters》2010,20(22):6730-6734
Novel hygromycin A derivatives bearing a variety of functionalized aminocyclitol moieties have been synthesized in an effort to increase the antibacterial activity and drug-like properties of this class of agents. A systematic study of the effect of alkylation and removal of the hydroxyls of the aminocyclitol directed us to a series of alkylated aminocyclitol derivatives with improved Gram-positive activity. 相似文献
963.
Amyloid formation plays a central role in the cause and progression of Alzheimer's disease. The major component of this amyloid is the amyloid-beta (A beta) peptide, which is currently the subject of intense study. This review discusses some recent studies in the area of A beta synthesis, purification and structural analysis. Also discussed are proposed mechanisms for A beta-induced neurotoxicity and some recent advances in the development of A beta-related therapeutic strategies. 相似文献
964.
K J Smith J D Wade A A Claasz L Otvos C Temelcos Y Kubota J M Hutson G W Tregear R A Bathgate 《Journal of peptide science》2001,7(9):495-501
The recently identified protein, insulin 3 (INSL3), has structural features that make it a bona fide member of the insulin superfamily. Its predicted amino acid sequence contains the classic two-peptide chain (A- and B-) structure with conserved cysteine residues that results in a disulphide bond disposition identical to that of insulin. Recently, the generation of insl3 knockout mice has demonstrated that testicular descent is blocked due to the failure of a specific ligament, the gubernaculum, to develop. The mechanism by which INSL3 exerts its action on the gubernaculum is currently unknown. The purpose of this study was to, for the first time, synthesize rat INSL3 and test its action on organ cultures of foetal rat gubernaculum. INSL3 also contains a cassette of residues Arg-X-X-X-Arg within the B-chain, a motif that is essential for characteristic activity of another related member of the superfamily, relaxin. Hence, the relaxin activity of rat INSL3 was also tested in two different relaxin bioassays. The primary structure of rat INSL3 was determined by deduction from its cDNA sequence and successfully prepared by solid phase peptide synthesis of the two constituent chains followed by their combination in solution. Following confirmation of its chemical integrity by a variety of analytical techniques, circular dichroism spectroscopy confirmed the presence of high beta-turn and alpha-helical content, with a remarkable spectral similarity to the synthetic ovine INSL3 peptide and to synthetic rat relaxin. The synthetic rat INSL3 bound with very low affinity to rat relaxin receptors and had no activity in a relaxin bioassay. Furthermore, it did not augment or antagonize relaxin activity. The rat INSL3 did however induce growth of foetal rat gubernaculum in whole organ cultures demonstrating that INSL3 has a direct action on this structure. 相似文献
965.
966.
Fnu Nagajyothi Louis M. Weiss Dazhi Zhao Wade Koba Linda A. Jelicks Min-Hui Cui Stephen M. Factor Philipp E. Scherer Herbert B. Tanowitz 《PLoS neglected tropical diseases》2014,8(10)
Background
Trypanosoma cruzi, the causative agent of Chagas disease, has high affinity for lipoproteins and adipose tissue. Infection results in myocarditis, fat loss and alterations in lipid homeostasis. This study was aimed at analyzing the effect of high fat diet (HFD) on regulating acute T. cruzi infection-induced myocarditis and to evaluate the effect of HFD on lipid metabolism in adipose tissue and heart during acute T. cruzi infection.Methodology/Principal Findings
CD1 mice were infected with T. cruzi (Brazil strain) and fed either a regular control diet (RD) or HFD for 35 days following infection. Serum lipid profile, tissue cholesterol levels, blood parasitemia, and tissue parasite load were analyzed to evaluate the effect of diet on infection. MicroPET and MRI analysis were performed to examine the morphological and functional status of the heart during acute infection. qPCR and immunoblot analysis were carried out to analyze the effect of diet on the genes involved in the host lipid metabolism during infection. Oil red O staining of the adipose tissue demonstrated reduced lipolysis in HFD compared to RD fed mice. HFD reduced mortality, parasitemia and cardiac parasite load, but increased parasite load in adipocytes. HFD decreased lipolysis during acute infection. Both qPCR and protein analysis demonstrated alterations in lipid metabolic pathways in adipose tissue and heart in RD fed mice, which were further modulated by HFD. Both microPET and MRI analyses demonstrated changes in infected RD murine hearts which were ameliorated by HFD.Conclusion/Significance
These studies indicate that Chagasic cardiomyopathy is associated with a cardiac lipidpathy and that both cardiac lipotoxicity and adipose tissue play a role in the pathogenesis of Chagas disease. HFD protected mice from T. cruzi infection-induced myocardial damage most likely due to the effects of HFD on both adipogenesis and T. cruzi infection-induced cardiac lipidopathy. 相似文献967.
Annette M. Hormann Frederick S. vom Saal Susan C. Nagel Richard W. Stahlhut Carol L. Moyer Mark R. Ellersieck Wade V. Welshons Pierre-Louis Toutain Julia A. Taylor 《PloS one》2014,9(10)
Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults. 相似文献
968.
Maria A. Sleddering Albert J. Markvoort Harish K. Dharuri Skhandhan Jeyakar Marieke Snel Peter Juhasz Moira Lynch Wade Hines Xiaohong Li Ingrid M. Jazet Aram Adourian Peter A. J. Hilbers Johannes W. A. Smit Ko Willems Van Dijk 《PloS one》2014,9(11)
Very low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin), obesity-associated (complement C3), and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers.
Trial Registration
Controlled-Trials.com ISRCTN76920690 相似文献969.
O'Hora J Cartwright A Wade CD Hough AD Shum GL 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(6):1586-1591
A number of studies have investigated the efficacy of several repetitions of proprioceptive neuromuscular facilitation stretching (PNF) and static stretching (SS). However, there is limited research comparing the effects of a single bout of these stretching maneuvers. The aim of this study was to compare the effectiveness of a single bout of a therapist-applied 30-second SS vs. a single bout of therapist-applied 6-second hamstring (agonist) contract PNF. Forty-five healthy subjects between the ages of 21 and 35 were randomly allocated to 1 of the 2 stretching groups or a control group, in which no stretching was received. The flexibility of the hamstring was determined by a range of passive knee extension, measured using a universal goniometer, with the subject in the supine position and the hip at 90° flexion, before and after intervention. A significant increase in knee extension was found for both intervention groups after a single stretch (SS group = 7.53°, p < 0.01 and PNF group = 11.80°, p < 0.01). Both interventions resulted in a significantly greater increase in knee extension when compared to the control group (p < 0.01). The PNF group demonstrated significantly greater gains in knee extension compared to the SS group (mean difference 4.27°, p < 0.01). It can be concluded that a therapist applied SS or PNF results in a significant increase in hamstring flexibility. A hamstring (agonist) contract PNF is more effective than an SS in a single stretching session. These findings are important to physiotherapists or trainers working in clinical and sporting environments. Where in the past therapists may have spent time conducting multiple repetitions of a PNF and an SS, a single bout of either technique may be considered just as effective. A key component of the study methodology was the exclusion of a warm-up period before stretching. Therefore, the findings of efficacy of a single PNF are of particular relevance in sporting environments and busy clinical settings where time may be limited. 相似文献
970.
Wouter D van Dijk Lisette van den Bemt Saskia van den Haak-Rongen Erik Bischoff Chris van Weel Johannes CCM in 't Veen Tjard RJ Schermer 《Respiratory research》2011,12(1):151