Familial Study on "Sinking pre-beta", the Lp(a) Lipoprotein, and its Relationship with Serum Lipids, Apolipoprotein A-I and B and Clinical Atherosclerosis

Peer Reviewe

Synergistic icephobic behaviour of swollen nitrile butadiene rubber graphene and/or carbon nanotube composites

Spontaneous change of adhesion of solidifying liquid on surfaces is of significant importance in materials technology where it finds applications such as anti-icing components operating in extreme environments like those of seals. In this work, nitrile butadiene rubber (NBR) composites reinforced with graphene, carbon nanotubes, and a mix of them after immersion in several fluids, experienced both a swelling and a reduction of the cross-link density that reduces ice adhesion, being this effect more evident for graphene containing samples. These results have been rationalized via a first principles atomistic modellization of interfaces formed by ice water of increasing thickness and graphene and scaling laws from fracture mechanics, revealing a clear synergy between swelling and nanocarbon phase in the icephobic nature of the composite, dictated by a competition between elastic modulus and adsorption energy. These findings could find an upscale in component validation readily applied to different areas where de-icing demands handling of large amount of environmental harmful agents.GG wants to thank CINECA [grant number HP10CN7DI0] and acknowledge PRACE for awarding us access to resource Marconi based in Italy at CINECA [Grant number Pra14_3664]. G.G. is similarly grateful to CARIT [grant number FCARITR17FR]” for supporting this research. MALM thanks the support from the MINECO [grant number MAT2016- 81138-R]. NMP is supported by the European Commission under the Graphene Flagship Core2 [WP14 “Composites” grant number 785219] and FET Proactive “Neurofibres” [grant number 732344]. NMP is supported by theItalian Ministry of Education, University and Research (MIUR) under the “Departments of Excellence” grant L.232/2016. LV is supported by the European Commission under the Graphene Flagship Core2 [WP14 “Composites” grant number 785219]. LV and GG rea supported by the Italian Ministry of Education, University and Research (MIUR) under the “Departments of Excellence” grant L.232/2016Peer Reviewe

Abdominal obesity, cardiometabolic risk and endocannabinoid system

Abdominal obesity is the most prevalent manifestation of metabolic syndrome and is of central importance in the definition of global cardiometabolic risk. Visceral adipose tissue releases a large number of bioactive mediators, which influence body weight homeostasis, insulin resistance, alterations in lipids, blood pressure, coagulation, fibrinolysis and inflammation, leading to increased risk of cardiovascular events and of type 2 diabetes. Lifestyle modification is the first-line approach to the management of abdominal obesity and metabolic syndrome. However for patients at higher risk, who cannot achieve an appreciable reduction in weight and in global cardiometabolic risk with lifestyle modification alone, an adjunctive long term pharmacotherapy should be considered. The endocannabinoid system activity regulates food intake and metabolic factors through cannabinoid-1 (CB1) receptor located in multiple sites, including hypothalamus and limbic forebrain, adipose tissue, skeletal muscle, liver and the gastrointestinal tract. Evidence suggests that CB1 receptor blockade offers a novel therapeutic strategy. Data from four phase III trials suggest that rimonabant, the first cannabinoid receptor inhibitor, modulates cardiometabolic risk factors, both through its impact on body weight and metabolic parameters such as HDL-cholesterol, tryglicerides, Hb1Ac, through direct pathways that are not related to weight loss

Fish intake, independent of apo(a) size, accounts for lower plasma lipoprotein(a) levels in Bantu fishermen of Tanzania: The Lugalawa Study.

Plasma lipoprotein(a) [Lp(a)] levels are largely genetically determined by sequences linked to the gene encoding apolipoprotein(a) [apo(a)], the distinct protein component of Lp(a). Apo(a) is highly polymorphic in length due to variation in the numbers of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a) are inversely correlated with apo(a) size. In 2 racially homogeneous Bantu populations from Tanzania differing in their dietary habits, we found that median plasma levels of Lp(a) were 48% lower in those living on a fish diet than in those living on a vegetarian diet. Considering the relationship between apo(a) size and Lp(a) plasma concentration, we have extensively evaluated apo(a) isoform distribution in the 2 populations to determine the impact of apo(a) size in the determination of Lp(a) values. The majority of individuals (82% of the fishermen and 80% of the vegetarians) had 2 expressed apo(a) alleles. Additionally, the fishermen had a high frequency of large apo(a) isoforms, whereas a higher frequency of small isoforms was found in the vegetarians. When subjects from the 2 groups were matched for apo(a) phenotype, the median Lp(a) value was 40% lower in Bantus on the fish diet than in those on the vegetarian diet. A significant inverse relationship was also found between plasma n-3 polyunsaturated fatty acids and Lp(a) levels (r=-0.24, P=0.01). The results of this study are consistent with the concept that a diet rich in n-3 polyunsaturated fatty acids, and not genetic differences, is responsible for the lower plasma levels of Lp(a) in the fish-eating Bantus and strongly suggest that a sustained fish-based diet is able to lower plasma levels of Lp(a)

Loss of apoB-100 secondary structure and conformation in hydroperoxide rich, electronegative LDL-

A subpopulation of low-density lipoproteins (LDL) is present in human plasma that contains lipid hydroperoxides and is more negatively charged (LDL(-)) than normal native LDL. By circular dichroism and tryptophan lifetime measurements we found that apoB-100 secondary structure is markedly decreased and its conformation is severely altered in LDL(-). The low tryptophan fluorescence intensity confirms the oxidative degradation of the lipoprotein, and the very long lifetime value of one of its decay components indicates a low polarity environment for the remaining unbleached residues. Either a peculiar folding or, most likely, a sinking of the apoB-100 into the lipid core can account for the observed long lifetime component. Oxidation in vitro produces a similar unfolding of the apolipoprotein but the lifetime of tryptophan fluorescence is shifted to lower values, indicating that the denatured apoprotein remains at the hydrophilic surface of the lipoprotein particle. A disordering and an increased polarity of the LDL(-) surface lipids was demonstrated by measuring the generalized polarization of 2-dimethylamino-6-lauroylnaphthalene (Laurdan). The looser monolayer packing apparently favors the new conformation of apoB-100 and its sinking into a more hydrophobic environment, possibly accounting for it reduced receptor binding properties