RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described neurodegenerative disorder of older adult carriers of premutation alleles (60–200 CGG repeats) in the fragile X mental retardation gene (FMR1). It has been proposed that FXTAS is an RNA-mediated neurodegenerative disease caused by the titration of RNA-binding proteins by the CGG repeats. To test this hypothesis, we utilize a transgenic Drosophila model of FXTAS that expresses a premutation-length repeat (90 CGG repeats) from the 5′ UTR of the human FMR1 gene and displays neuronal degeneration. Here, we show that overexpression of RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppresses the phenotype of the CGG transgenic fly. Furthermore, we show that hnRNP A2/B1 directly interacts with riboCGG repeats and that the CUGBP1 protein interacts with the riboCGG repeats via hnRNP A2/B1

Analyzing and Mapping Sweat Metabolomics by High-Resolution NMR Spectroscopy

The content of human sweat is studied by high-resolution NMR, and the majority of organic components most often found in sweat of conditionally healthy people are identified. Original and simple tools are designed for sweat sampling from different areas of human body. The minimal surface area needed for sampling is in the range of 50–100 cm2. On all the surface parts of the human body examined in this work, the main constituents forming a sweat metabolic profile are lactate, glycerol, pyruvate, and serine. The only exception is the sole of the foot (planta pedis), where trace amounts of glycerol are found. An attempt is made to explain the presence of specified metabolites and their possible origin

Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in OffspringSummary

Background & Aims: The obesity-associated nonalcoholic fatty liver disease represents a common cause of pediatric liver diseases, including the pediatric liver cancer hepatoblastoma. The mechanisms behind the development of fatty liver in children are not yet known. We examined the role of the C/EBPα-p300 pathway in the development of maternal obesity-associated fatty liver phenotype in offspring. Methods: Because the ability of C/EBPα to promote fatty liver phenotype is enhanced by CDK4-mediated phosphorylation of C/EBPα at Ser193 and subsequent formation of C/EBPα-p300 complexes, we used wild-type (WT) and C/EBPα-S193D and C/EBPα-S193A mutant mice to study the effects of maternal high-fat diet (HFD) on the liver health of offspring. The females of these mouse lines were fed an HFD before mating, and the pups were further subjected to either an HFD or a normal diet for 12 weeks. Results: WT female mice on the HFD before and during pregnancy and their subsequent offspring on the HFD had severe fatty liver, fibrosis, and an increased rate of liver proliferation. However, the HFD in C/EBPα-S193A mice did not cause development of these disorders. In HFD-HFD treated WT mice, C/EBPα is phosphorylated at Ser193 and forms complexes with p300, which activate expression of genes involved in development of fatty liver, fibrosis, and proliferation. However, S193A-C/EBPα mice do not have complexes of C/EBPα-S193A with p300, leading to a lack of activation of genes of fatty liver, fibrosis, and proliferation. The mutant C/EBPα-S193D mice have accelerated cdk4-dependent pathway and have developed steatosis at early stages. Conclusions: These studies identified the epigenetic cause of obese pregnancy–associated liver diseases and suggest a potential therapy based on inhibition of cdk4-ph-S193-C/EBPα-p300 pathway

Influence of the Preparation "Nicavet-1000" on a Morphofunctional Condition of some Organs of Rats at Experimental Aluminium Intoxication

During the conducted research, it is established that aluminium chloride intoxication leads to the considerable changes of composition of red blood, development of a hypercalcemia and change of a bone structure of animals. A number of significant morphofunctional changes in the hippocampus of the examined animals are also noted. The use of the tissue preparation "Nicavet-1000" leads to the normalization of both hematocrit and other parameters of red blood, as well as to the intensification of erythropoiesis. Use of the preparation "Nicavet-1000", judging from the results of research, prevents pathological changes in a bone tissue, caused by aluminium chloride. "Nicavet-1000" leads to the expressed normalization of both the morphological, and micromorphometric parameters characterizing a hippocampus of rats

Influence of the Preparation "Nicavet-1000" on a Morphofunctional Condition of some Organs of Rats at Experimental Aluminium Intoxication

During the conducted research, it is established that aluminium chloride intoxication leads to the considerable changes of composition of red blood, development of a hypercalcemia and change of a bone structure of animals. A number of significant morphofunctional changes in the hippocampus of the examined animals are also noted. The use of the tissue preparation "Nicavet-1000" leads to the normalization of both hematocrit and other parameters of red blood, as well as to the intensification of erythropoiesis. Use of the preparation "Nicavet-1000", judging from the results of research, prevents pathological changes in a bone tissue, caused by aluminium chloride. "Nicavet-1000" leads to the expressed normalization of both the morphological, and micromorphometric parameters characterizing a hippocampus of rats

Dynamics of Oligomer Formation by Denatured Carbonic Anhydrase II

Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. Many proteins unrelated to amyloidoses also fibrillate at the appropriate conditions. These proteins serve as a model for studying the processes of protein misfolding, oligomerization and fibril formation. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation. The urea-induced unfolding of bovine carbonic anhydrase II, BCA II, is characterized by a combination of high-resolution NMR, circular dichroism spectroscopy and small angle X-ray scattering. It is shown that the formation of associates of protein molecules in complex with solvent (water and urea), APS, takes place in the presence of 4–6 M urea. The subsequent increase in urea concentration to 8 M is accompanied by a disruption of APS and leads to a complete unfolding of a protein molecule. Analysis of BCA II self-association in the presence of 4.2 M urea revealed that APS are relatively large mostly β-structural blocks with the averaged molecular mass of 190–220 kDa. This work also demonstrates some novel NMR-based methodological approaches that provide useful information on protein self-association

Calcification of Various Bioprosthetic Materials in Rats: Is It Really Different?

The causes of heart valve bioprosthetic calcification are still not clear. In this paper, we compared the calcification in the porcine aorta (Ao) and the bovine jugular vein (Ve) walls, as well as the bovine pericardium (Pe). Biomaterials were crosslinked with glutaraldehyde (GA) and diepoxide (DE), after which they were implanted subcutaneously in young rats for 10, 20, and 30 days. Collagen, elastin, and fibrillin were visualized in non-implanted samples. Atomic absorption spectroscopy, histological methods, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to study the dynamics of calcification. By the 30th day, calcium accumulated most intensively in the collagen fibers of the GA-Pe. In elastin-rich materials, calcium deposits were associated with elastin fibers and localized differences in the walls of Ao and Ve. The DE-Pe did not calcify at all for 30 days. Alkaline phosphatase does not affect calcification since it was not found in the implant tissue. Fibrillin surrounds elastin fibers in the Ao and Ve, but its involvement in calcification is questionable. In the subcutaneous space of young rats, which are used to model the implants’ calcification, the content of phosphorus was five times higher than in aging animals. We hypothesize that the centers of calcium phosphate nucleation are the positively charged nitrogen of the pyridinium rings, which is the main one in fresh elastin and appears in collagen as a result of GA preservation. Nucleation can be significantly accelerated at high concentrations of phosphorus in biological fluids. The hypothesis needs further experimental confirmation

¹⁴N-NMR spectrum of human sweat from forehead (male).

<p>¹⁴N-NMR spectrum of human sweat from forehead (male).</p

¹H-NMR spectrum of sweat from child back (A) and male sole of foot (B).

<p>In contrast to spectra of sweat from human back and forehead (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028824#pone-0028824-g001" target="_blank">Figs. 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028824#pone-0028824-g002" target="_blank">2</a>), the observed signal of glycerol in the 3.5–3.8 ppm region of NMR spectra was very weak.</p

¹H-NMR spectrum of sweat from human back, «sugar region» is highlighted (male).

<p>¹H-NMR spectrum of sweat from human back, «sugar region» is highlighted (male).</p