The Ubiquitin-Proteasome System and Inflammatory Activity in Diabetic Atherosclerotic Plaques

The role of ubiquitin-proteasome system in the accelerated atherosclerotic progression of diabetic patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic diabetic and nondiabetic patients, as well as the effect of rosiglitazone, a peroxisome proliferator–activated receptor (PPAR)-γ activator, in diabetic plaques. Plaques were obtained from 46 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Diabetic patients received 8 mg rosiglitazone (n = 23) or placebo (n = 23) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-cells (CD3), inflammatory cells (HLA-DR), ubiquitin, proteasome 20S activity, nuclear factor (NF)-κB, inhibitor of κB (IκB)-β, tumor necrosis factor (TNF)-α, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Compared with nondiabetic plaques, diabetic plaques had more macrophages, T-cells, and HLA-DR+ cells (P < 0.001); more ubiquitin, proteasome 20S activity (TNF-α), and NF-κB (P < 0.001); and more markers of oxidative stress (nitrotyrosine and O2− production) and MMP-9 (P < 0.01), along with a lesser collagen content and IκB-β levels (P < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated diabetic plaques presented less inflammatory cells (P < 0.01); less ubiquitin, proteasome 20S, TNF-α, and NF-κB (P < 0.01); less nitrotyrosine and superoxide anion production (P < 0.01); and greater collagen content (P < 0.01), indicating a more stable plaque phenotype. Similar findings were obtained in circulating monocytes obtained from the two groups of diabetic patients and cultured in the presence or absence of rosiglitazone (7.0 μmol/l). Ubiquitin-proteasome over-activity is associated with enhanced inflammatory reaction and NF-κB expression in diabetic plaques. The inhibition of ubiquitin-proteasome activity in atherosclerotic lesions of diabetic patients by rosiglitazone is associated with morphological and compositional characteristics of a potential stable plaque phenotype, possibly by downregulating NF-κB-mediated inflammatory pathways

The Zea mays mutants opaque-2 and opaque-7 disclose extensive changes in endosperm metabolism as revealed by protein, amino acid, and transcriptome-wide analyses

<p>Abstract</p> <p>Background</p> <p>The changes in storage reserve accumulation during maize (<it>Zea mays </it>L.) grain maturation are well established. However, the key molecular determinants controlling carbon flux to the grain and the partitioning of carbon to starch and protein are more elusive. The <it>Opaque-2 </it>(<it>O2</it>) gene, one of the best-characterized plant transcription factors, is a good example of the integration of carbohydrate, amino acid and storage protein metabolisms in maize endosperm development. Evidence also indicates that the <it>Opaque-7 </it>(<it>O7</it>) gene plays a role in affecting endosperm metabolism. The focus of this study was to assess the changes induced by the <it>o2 </it>and <it>o7 </it>mutations on maize endosperm metabolism by evaluating protein and amino acid composition and by transcriptome profiling, in order to investigate the functional interplay between these two genes in single and double mutants.</p> <p>Results</p> <p>We show that the overall amino acid composition of the mutants analyzed appeared similar. Each mutant had a high Lys and reduced Glx and Leu content with respect to wild type. Gene expression profiling, based on a unigene set composed of 7,250 ESTs, allowed us to identify a series of mutant-related down (17.1%) and up-regulated (3.2%) transcripts. Several differentially expressed ESTs homologous to genes encoding enzymes involved in amino acid synthesis, carbon metabolism (TCA cycle and glycolysis), in storage protein and starch metabolism, in gene transcription and translation processes, in signal transduction, and in protein, fatty acid, and lipid synthesis were identified. Our analyses demonstrate that the mutants investigated are pleiotropic and play a critical role in several endosperm-related metabolic processes. Pleiotropic effects were less evident in the <it>o7 </it>mutant, but severe in the <it>o2 </it>and <it>o2o7 </it>backgrounds, with large changes in gene expression patterns, affecting a broad range of kernel-expressed genes.</p> <p>Conclusion</p> <p>Although, by necessity, this paper is descriptive and more work is required to define gene functions and dissect the complex regulation of gene expression, the genes isolated and characterized to date give us an intriguing insight into the mechanisms underlying endosperm metabolism.</p

An interdisciplinary approach to evaluating the need for assistive technology reduces equipment abandonment.

Assistive technology makes up a substantial portion of the direct cost of multiple sclerosis (MS). Equipment abandonment results in the needs of the disabled individual being unmet and places stress on the resources available for the funding of such equipment. The aim of the study was to demonstrate whether an interdisciplinary approach to evaluating and prescribing assistive technology reduces equipment abandonment in persons with MS. Data concerning assistive devices acquired by patients being followed at a rehabilitation centre in northern Italy from January 1997 to December 2002, were included in the study. Through December 1999, a physician in physical medicine and rehabilitation prescribed equipment based on a recommendation from the physical therapist. From 2000 to 2002, patients were evaluated following a standardized protocol implemented by an interdisciplinary team comprised of a physical therapist, occupational therapist, physician in physical medicine and rehabilitation and psychologist. Assistive technology obtained during the study period was divided into two datasets based on the year that the aid was obtained: pre-intervention (January 1997 to December 1999) and intervention (January 2000 to December 2002). The analysis included a comparison of the two datasets on number and types of equipment abandoned, timing of abandonment and reasons why devices were abandoned. Fifty-four subjects obtained 151 assistive devices during the study period, 67 devices during pre-intervention and 84 with the intervention. The majority of devices were abandoned immediately or within the first year following obtainment in both groups. A comparison of the number of devices obtained during pre-intervention with those obtained during the intervention showed that the rate of equipment abandonment decreased significantly from 37.3 to 9.5%. An interdisciplinary approach to evaluating assistive technology needs does decrease the risk of equipment abandonment, although it does not completely solve the problem

INAA at the top of the world: elemental characterization and analysis of airborne particulate matter collected at Himalayas at 5,100 m high.

In 1990, following an agreement with the Royal Nepal Academy of Science, the Italian National Research Council (CNR) installed a scientific laboratory (Pyramid) at 5,050 m (s.l.) in the Himalayan region. Among the environmental related researches, the task project RATEAP (Remote Areas Trace Elements Atmospheric Pollution), started in 2001, aims at obtaining information about the chemical composition of the high altitude airborne particulate matter. During the period of March April 2002 series of samplings have been carried out by pump aspiration. Samples of total suspended particles (TSP) as well as of the particles size fraction PM10 and PM2.5 have been collected and submitted to INAA for the determination of more than 30 elements present at nanogram levels, in few micrograms of air dust. Data quality assurance has been performed by the analysis of different NIST SRMs and, in particular, the SRM 2783 Air Particulate on Filter Media

Monitoring media pluralism in the digital era : application of the Media Pluralism Monitor in the European Union, Albania, Montenegro, Republic of North Macedonia, Serbia & Turkey in the year 2020

This report was co-funded by the European Commissio