HDAC3 is a molecular brake of the metabolic switch supporting white adipose tissue browning.

White adipose tissue (WAT) can undergo a phenotypic switch, known as browning, in response to environmental stimuli such as cold. Post-translational modifications of histones have been shown to regulate cellular energy metabolism, but their role in white adipose tissue physiology remains incompletely understood. Here we show that histone deacetylase 3 (HDAC3) regulates WAT metabolism and function. Selective ablation of Hdac3 in fat switches the metabolic signature of WAT by activating a futile cycle of de novo fatty acid synthesis and β-oxidation that potentiates WAT oxidative capacity and ultimately supports browning. Specific ablation of Hdac3 in adipose tissue increases acetylation of enhancers in Pparg and Ucp1 genes, and of putative regulatory regions of the Ppara gene. Our results unveil HDAC3 as a regulator of WAT physiology, which acts as a molecular brake that inhibits fatty acid metabolism and WAT browning.Histone deacetylases, such as HDAC3, have been shown to alter cellular metabolism in various tissues. Here the authors show that HDAC3 regulates WAT metabolism by activating a futile cycle of fatty acid synthesis and oxidation, which supports WAT browning

Insight on colorectal carcinoma infiltration by studying perilesional extracellular matrix

The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential

High Abundance Proteins Depletion vs Low Abundance Proteins Enrichment: Comparison of Methods to Reduce the Plasma Proteome Complexity

BACKGROUND: To date, the complexity of the plasma proteome exceeds the analytical capacity of conventional approaches to isolate lower abundance proteins that may prove to be informative biomarkers. Only complex multistep separation strategies have been able to detect a substantial number of low abundance proteins (<100 ng/ml). The first step of these protocols is generally the depletion of high abundance proteins by the use of immunoaffinity columns or, alternatively, the enrichment of by the use of solid phase hexapeptides ligand libraries. METHODOLOGY/PRINCIPAL FINDINGS: Here we present a direct comparison of these two approaches. Following either approach, the plasma sample was further fractionated by SCX chromatography and analyzed by RP-LC-MS/MS with a Q-TOF mass spectrometer. The depletion of the 20 most abundant plasma proteins allowed the identification of about 25% more proteins than those detectable following low abundance proteins enrichment. The two datasets are partially overlapping and the identified proteins belong to the same order of magnitude in terms of plasma concentration. CONCLUSIONS/SIGNIFICANCE: Our results show that the two approaches give complementary results. However, the enrichment of low abundance proteins has the great advantage of obtaining much larger amount of material that can be used for further fractionations and analyses and emerges also as a cheaper and technically simpler approach. Collectively, these data indicate that the enrichment approach seems more suitable as the first stage of a complex multi-step fractionation protocol

Factors affecting adherence to guidelines for antithrombotic therapy in elderly patients with atrial fibrillation admitted to internal medicine wards

Current guidelines for ischemic stroke prevention in atrial fibrillation or flutter (AFF) recommend Vitamin K antagonists (VKAs) for patients at high-intermediate risk and aspirin for those at intermediate-low risk. The cost-effectiveness of these treatments was demonstrated also in elderly patients. However, there are several reports that emphasize the underuse of pharmacological prophylaxis of cardio-embolism in patients with AFF in different health care settings. AIMS: To evaluate the adherence to current guidelines on cardio-embolic prophylaxis in elderly (> 65 years old) patients admitted with an established diagnosis of AFF to the Italian internal medicine wards participating in REPOSI registry, a project on polypathologies/polytherapies stemming from the collaboration between the Italian Society of Internal Medicine and the Mario Negri Institute of Pharmacological Research; to investigate whether or not hospitalization had an impact on guidelines adherence; to test the role of possible modifiers of VKAs prescription. METHODS: We retrospectively analyzed registry data collected from January to December 2008 and assessed the prevalence of patients with AFF at admission and the prevalence of risk factors for cardio-embolism. After stratifying the patients according to their CHADS(2) score the percentage of appropriateness of antithrombotic therapy prescription was evaluated both at admission and at discharge. Univariable and multivariable logistic regression models were employed to verify whether or not socio-demographic (age >80years, living alone) and clinical features (previous or recent bleeding, cranio-facial trauma, cancer, dementia) modified the frequency and modalities of antithrombotic drugs prescription at admission and discharge. RESULTS: Among the 1332 REPOSI patients, 247 were admitted with AFF. At admission, CHADS(2) score was ≥ 2 in 68.4% of patients, at discharge in 75.9%. Among patients with AFF 26.5% at admission and 32.8% at discharge were not on any antithrombotic therapy, and 43.7% at admission and 40.9% at discharge were not taking an appropriate therapy according to the CHADS(2) score. The higher the level of cardio-embolic risk the higher was the percentage of antiplatelet- but not of VKAs-treated patients. At admission or at discharge, both at univariable and at multivariable logistic regression, only an age >80 years and a diagnosis of cancer, previous or active, had a statistically significant negative effect on VKAs prescription. Moreover, only a positive history of bleeding events (past or present) was independently associated to no VKA prescription at discharge in patients who were on VKA therapy at admission. If heparin was considered as an appropriate therapy for patients with indication for VKAs, the percentage of patients admitted or discharged on appropriate therapy became respectively 43.7% and 53.4%. CONCLUSION: Among elderly patients admitted with a diagnosis of AFF to internal medicine wards, an appropriate antithrombotic prophylaxis was taken by less than 50%, with an underuse of VKAs prescription independently of the level of cardio-embolic risk. Hospitalization did not improve the adherence to guideline

Case–control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk

Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg213His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case–control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens

Production and quality of biomass fuels from mechanized collection and processing of vineyard pruning residues

Vineyards cover about eight millions of hectares worldwide and their annual pruning generates a large amount of ligno-cellulosic biomass, potentially available for industrial and energy use. Commercial pruning residue harvesters are now available, which may allow cost-effective recovery. The study aimed at determining the quantity and the quality of pruning residues potentially derived from vineyard management. Data were obtained from 17 fields in Northern and Central Italy. Fields were harvested with seven different machines. The experimental design adapted to the necessities of field trials, but was adequate for testing the main sources of variability. Net residue yield varies around 1 oven dry tonne per hectare, with minor differences between grape varietals and harvesting technologies. Losses are still high, and are generally related to ineffective management techniques. Moisture content at harvest varies between 40% and 45%, whereas the higher heating value is slightly lower than that of forest fuels. Comminuted vineyard residues are unsuitable for firing residential boilers, due to the frequent presence of oversize and/or undersize particles. The application of pesticides does not result in any significant contamination with noxious chemicals, because these products are almost completely weathered before residues are recovered. In wine-producing regions, the recovery of vineyard pruning residue may represent a substantial source of industrial bio-fuel