Effects of DNA supercoiling on chromatin architecture

Disruptions in chromatin structure are necessary for the regulation of eukaryotic genomes, from remodelling of nucleosomes at the base pair level through to large-scale chromatin domains that are hundreds of kilobases in size. RNA polymerase is a powerful motor which, prevented from turning with the tight helical pitch of the DNA, generates over-wound DNA ahead of itself and under-wound DNA behind. Mounting evidence supports a central role for transcription-dependent DNA supercoiling in disrupting chromatin structure at all scales. This supercoiling changes the properties of the DNA helix in a manner that substantially alters the binding specificity of DNA binding proteins and complexes, including nucleosomes, polymerases, topoisomerases and transcription factors. For example, transient over-wound DNA destabilises nucleosome core particles ahead of a transcribing polymerase, whereas under-wound DNA facilitates pre-initiation complex formation, transcription factor binding and nucleosome core particle association behind the transcribing polymerase. Importantly, DNA supercoiling can also dissipate through DNA, even in a chromatinised context, to influence both local elements and large chromatin domains. We propose a model in which changes in unconstrained DNA supercoiling influences higher levels of chromatin organisation through the additive effects of DNA supercoiling on both DNA-protein and DNA-nucleosome interactions. This model links small-scale changes in DNA and chromatin to the higher-order fibre and large-scale chromatin structures, providing a mechanism relating gene regulation to chromatin architecture in vivo

High degree of BMI misclassification of malnutrition among Swedish elderly population: Age-adjusted height estimation using knee height and demispan.

Background/Objectives:The degree of misclassification of obesity and undernutrition among elders owing to inaccurate height measurements is investigated using height predicted by knee height (KH) and demispan equations.Subjects/Methods:Cross-sectional investigation was done among a random heterogeneous sample from five municipalities in Southern Sweden from a general population study 'Good Aging in Skåne' (GÅS). The sample comprised two groups: group 1 (KH) including 2839 GÅS baseline participants aged 60-93 years with a valid KH measurement and group 2 (demispan) including 2871 GÅS follow-up examination participants (1573 baseline; 1298 new), aged 60-99 years, with a valid demispan measurement. Participation rate was 80%. Height, weight, KH and demispan were measured. KH and demispan equations were formulated using linear regression analysis among participants aged 60-64 years as reference. Body mass index (BMI) was calculated in kg/m(2).Results:Undernutrition prevalences in men and women were 3.9 and 8.6% by KH, compared with 2.4 and 5.4% by standard BMI, and more pronounced for all women aged 85+ years (21% vs 11.3%). The corresponding value in women aged 85+ years by demispan was 16.5% vs 10% by standard BMI. Obesity prevalences in men and women were 17.5 and 14.6% by KH, compared with 19.0 and 20.03% by standard BMI. Values among women aged 85+ years were 3.7% vs 10.4% by KH and 6.5% vs 12.7% by demispan compared with the standard.Conclusions:There is an age-related misclassification of undernutrition and obesity attributed to inaccurate height estimation among the elderly. This could affect the management of patients at true risk. We therefore propose using KH- and demispan-based formulae to address this issue.European Journal of Clinical Nutrition advance online publication, 10 September 2014; doi:10.1038/ejcn.2014.183

Hypoglycemic effect of <it>Carica papaya</it> leaves in streptozotocin-induced diabetic rats

<p>Abstract</p> <p>Background</p> <p>Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of <it>C. papaya</it> leaves in diabetic rats. Several studies have reported that some parts of the <it>C. papaya</it> plant exert hypoglycemic effects in both animals and humans.</p> <p>Methods</p> <p>Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of <it>C. papaya</it> was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks.</p> <p>Results</p> <p>The aqueous extract of <it>Carica papaya</it> (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, <it>C. papaya</it> could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, <it>C. papaya</it> prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of <it>C. papaya</it> extract was also detected in diabetic rats.</p> <p>Conclusions</p> <p>This study showed that the aqueous extract of <it>C. papaya</it> exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas.</p