329 research outputs found
Discord of the Devil: The Pueblo Revolt, the Salem Witchcraft Trials and how the Spirit World Helped Make America
Teaching Note - Toward Twenty-first-century Teaching: Interdisciplinarity at Bridgewater and Beyond
South African indigenous fruits ā Underutilized resource for boosting daily antioxidant intake among local indigent populations?
Consuming more than seven portions of fruit and vegetables daily substantially lowers the risk of mortality from any cause, yet many South Africans living below the poverty line have a very low or even zero intake of fruit and vegetables. Advice on the importance of consuming a healthy, and at the same time affordable diet needs to be provided by suggesting alternatives among indigenous plants that are nutritionally superior to āexoticā fruits. But to what extent could antioxidant intake be boosted through the ingestion of selected indigenous fruits? Ten indigenous South African fruits were evaluated for their antioxidant activity and compared with blueberry and cranberry. An Antioxidant Potency Composite Index was drawn up based on the results of three equally weighted assays, namely Total Phenolic Content (FCR), Trolox Equivalent Antioxidant Capacity (TEAC) and Total Antioxidant Capacity (H-ORACFL+L-ORACFFL). The antioxidant potency rankings obtained were as follows: wild plum > wild olive > colpoon > blueberry > christmas berry > crossberry > waterberry > cranberry > tortoise berry > bietou > num-num > sour fig. Blueberry and cranberry ranked 5th and 9th, respectively. It was shown that by introducing servings of as little as 25 g of wild plum, waterberry, num num or sour fig into the diet, the daily antioxidant intake can be boosted to within an acceptable range to support health. All of these freely available fruits are known and have been traditionally used by rural communities in South Africa.Keywords: antioxidant capacity (AOC), antioxidant potency composite index, oxygen radical antioxidant capacity (ORAC), total phenolic content (TPC), trolox equivalent antioxidant capacity (TEAC
Role of protein kinase C-delta in the regulation of collagen gene expression in scleroderma fibroblasts
Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a \u3e80% reduction in COL1A1 mRNA, and a \u3e70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections with COL1A1 promoter deletion constructs demonstrated that rottlerin profoundly reduced COL1A1 transcription and that this effect required a 129-bp promoter region encompassing nucleotides -804 to -675. This COL1A1 segment imparted rottlerin sensitivity to a heterologous promoter. Cotransfections of COL1A1 promoter constructs with a dominant-negative PKC-delta expression plasmid showed that suppression of this kinase silenced COL1A1 promoter activity. The results indicate that PKC-delta participates in the upregulation of collagen gene transcription in SSc and suggest that treatment with PKC-delta inhibitors could suppress fibrosis in this disease
Quality of life, coping ability, and metabolic control in patients with type 1 diabetes managed by group care and a carbohydrate counting program.
Group care is a clinical-pedagogic model in which traditional routine visits are substituted by sessions of group education. This approach improves quality of life and metabolic control in patients with type 2 diabetes (1) but only quality of life in those with type 1 diabetes (2). The latter must match multiple daily insulin administrations with blood glucose monitoring, dietary intake, and energy expenditure (3). We hypothesized that to improve their coping strategies, patients with type 1 diabetes need more specific training in the technical aspects of day-to-day management of insulin therapy. To verify this, we studied the effects of embedding a carbohydrate counting program within group care on quality of life, knowledge
When āpervertsā were religious: the Protestant sexualisation of asceticism in nineteenth-century Britain, India and Ireland
Anti-Catholic polemics from the mid-nineteenth century made frequent comparison between religious practices in Britain, Ireland and India. The supposed atrocities taking place at locations such as Lough Dearg in Country Donegal and at āJuggernautā (Jagganath) at Puri were denounced in terms which hinted strongly at a striking combination of extreme asceticism and perverse sexual enjoyment. In the same period the word āperversionā, which had hitherto referred to apostasy, started to develop connotations of sexual deviance. Protestant sexualised readings of Catholic and Hindu asceticism appear to have been an important site for the development of conceptions of deviant sexuality in general and masochism in particular
Simvastatin inhibits TGFĪ²1-induced fibronectin in human airway fibroblasts
<p>Abstract</p> <p>Background</p> <p>Bronchial fibroblasts contribute to airway remodelling, including airway wall fibrosis. Transforming growth factor (TGF)-Ī²1 plays a major role in this process. We previously revealed the importance of the mevalonate cascade in the fibrotic response of human airway smooth muscle cells. We now investigate mevalonate cascade-associated signaling in TGFĪ²1-induced fibronectin expression by bronchial fibroblasts from non-asthmatic and asthmatic subjects.</p> <p>Methods</p> <p>We used simvastatin (1-15 Ī¼M) to inhibit 3-hydroxy-3-methlyglutaryl-coenzyme A (HMG-CoA) reductase which converts HMG-CoA to mevalonate. Selective inhibitors of geranylgeranyl transferase-1 (GGT1; GGTI-286, 10 Ī¼M) and farnesyl transferase (FT; FTI-277, 10 Ī¼M) were used to determine whether GGT1 and FT contribute to TGFĪ²1-induced fibronectin expression. In addition, we studied the effects of co-incubation with simvastatin and mevalonate (1 mM), geranylgeranylpyrophosphate (30 Ī¼M) or farnesylpyrophosphate (30 Ī¼M).</p> <p>Results</p> <p>Immunoblotting revealed concentration-dependent simvastatin inhibition of TGFĪ²1 (2.5 ng/ml, 48 h)-induced fibronectin. This was prevented by exogenous mevalonate, or isoprenoids (geranylgeranylpyrophosphate or farnesylpyrophosphate). The effects of simvastatin were mimicked by GGTI-286, but not FTI-277, suggesting fundamental involvement of GGT1 in TGFĪ²1-induced signaling. Asthmatic fibroblasts exhibited greater TGFĪ²1-induced fibronectin expression compared to non-asthmatic cells; this enhanced response was effectively reduced by simvastatin.</p> <p>Conclusions</p> <p>We conclude that TGFĪ²1-induced fibronectin expression in airway fibroblasts relies on activity of GGT1 and availability of isoprenoids. Our results suggest that targeting regulators of isoprenoid-dependent signaling holds promise for treating airway wall fibrosis.</p
CTGF expression is up-regulated by PROK1 in early pregnancy and influences HTR-8/Svneo cell adhesion and network formation
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Arterial stiffening in western diet-fed mice is associated with increased vascular elastin, transforming growth factor-Ć, and plasma neuraminidase
Consumption of excess fat and carbohydrate (Western diet, WD) is associated with alterations in the structural characteristics of blood vessels. This vascular remodeling contributes to the development of cardiovascular disease, particularly as it affects conduit and resistance arteries. Vascular remodeling is often associated with changes in the elastin-rich internal elastic lamina (IEL) and the activation of transforming growth factor (TGF)-Ć. In addition, obesity and type II diabetes have been associated with increased serum neuraminidase, an enzyme known to increase TGF-Ć cellular output. Therefore, we hypothesized that WD-feeding would induce structural modifications to the IEL of mesenteric resistance arteries in mice, and that these changes would be associated with increased levels of circulating neuraminidase and the up-regulation of elastin and TGF-Ć in the arterial wall. To test this hypothesis, a WD, high in fat and sugar, was used to induce obesity in mice, and the effect of this diet on the structure of mesenteric resistance arteries was investigated. 4-week old, Post-weaning mice were fed either a normal diet (ND) or WD for 16 weeks. Mechanically, arteries from WD-fed mice were stiffer and less distensible, with marginally increased wall stress for a given strain, and a significantly increased Young's modulus of elasticity. Structurally, the wall cross-sectional area and the number of fenestrae found in the internal elastic lamina (IEL) of mesenteric arteries from mice fed a WD were significantly smaller than those of arteries from the ND-fed mice. There was also a significant increase in the volume of elastin, but not collagen in arteries from the WD cohort. Plasma levels of neuraminidase and the amount of TGF-Ć in mesenteric arteries were elevated in mice fed a WD, while ex vivo, cultured vascular smooth muscle cells exposed to neuraminidase secreted greater amounts of tropoelastin and TGF-Ć than those exposed to vehicle. These data suggest that consumption of a diet high in fat and sugar causes stiffening of the vascular wall in resistance arteries through a process that may involve increased neuraminidase and TGF-Ć activity, elevated production of elastin, and a reduction in the size and number of fenestrae in the arterial IEL
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