Publications

Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation within the liver affecting 1 in 4 people worldwide. As the new silent killer of the twenty-first century, NAFLD impacts on both the request and the availability of new liver donors. The liver is the first line of defense against endogenous and exogenous metabolites and toxins. It also retains the ability to switch between different metabolic pathways according to food type and availability. This ability becomes a disadvantage in obesogenic societies where most people choose a diet based on fats and carbohydrates while ignoring vitamins and fiber. The chronic exposure to fats and carbohydrates induces dramatic changes in the liver zonation and triggers the development of insulin resistance. Common believes on NAFLD and different diets are based either on epidemiological studies, or meta-analysis, which are not controlled evidences; in most of the cases, they are biased on test-subject type and their lifestyles. The highest success in reverting NAFLD can be attributed to diets based on high protein instead of carbohydrates. In this review, we discuss the impact of NAFLD on body metabolic plasticity. We also present a detailed analysis of the most recent studies that evaluate high-protein diets in NAFLD with a special focus on the liver and the skeletal muscle protein metabolisms.

JTD Keywords: High protein diet, Low carbohydrates, NAFLD, NASH, Physical activity

One mechanism leading to neurodegeneration during Alzheimer's Disease (AD) is amyloid beta peptide (A beta)-induced neurotoxicity. Among the factors proposed to potentiate A beta toxicity is its covalent modification through carbohydrate-derived advanced glycation endproducts (AGEs). Other experimental evidence, though, indicates that certain polymeric carbohydrates like the glycosaminoglycan (GAG) chains found in proteoglycan molecules attenuate the neurotoxic effect of A beta in primary neuronal cultures. Pretreatment of the 42-residue A beta fragment (A beta(1-42)) with the ubiquitous brain carbohydrates, glucose, fructose, and the GAG chondroitin sulfate B (CSB) inhibits A beta beta(1-42)-induced apoptosis and reduces the peptide neurotoxicity on neuroblastoma cells, a cytoprotective effect that is partially reverted by AGE inhibitors such as pyridoxamine and L-carnosine. Thioflavin T fluorescence measurements indicate that at concentrations close to physiological, only CSB promotes the formation of A beta amyloid fibril structure. Atomic force microscopy imaging and Western blot analysis suggest that glucose favours the formation of globular oligomeric structures derived from aggregated species. Our data suggest that at short times carbohydrates reduce A beta(1-42) toxicity through different mechanisms both dependent and independent of AGE formation.

JTD Keywords: Alzheimer's disease, Advanced glycation endproducts, Amyloid fibrils, Amyloid beta peptide, Apoptosis, Carbohydrates, Glycosaminoglycans

The Cambrian explosion of life was a relatively short period approximately 540 Ma that marked a generalized acceleration in the evolution of most animal phyla, but the trigger of this key biological event remains elusive. Sponges are the oldest extant Precambrian metazoan phylum and thus a valid model to study factors that could have unleashed the rise of multicellular animals. One such factor is the advent of self-/non-self-recognition systems, which would be evolutionarily beneficial to organisms to prevent germ-cell parasitism or the introduction of deleterious mutations resulting from fusion with genetically different individuals. However, the molecules responsible for allorecognition probably evolved gradually before the Cambrian period, and some other (external) factor remains to be identified as the missing triggering event. Sponge cells associate through calcium-dependent, multivalent carbohydrate-carbohydrate interactions of the g200 glycan found on extracellular proteoglycans. Single molecule force spectroscopy analysis of g200-g200 binding indicates that calcium affects the lifetime (+Ca/-Ca: 680 s/3 s) and bond reaction length (+Ca/-Ca: 3.47 /2.27). Calculation of mean g200 dissociation times in low and high calcium within the theoretical framework of a cooperative binding model indicates the nonlinear and divergent characteristics leading to either disaggregated cells or stable multicellular assemblies, respectively. This fundamental phenomenon can explain a switch from weak to strong adhesion between primitive metazoan cells caused by the well-documented rise in ocean calcium levels at the end of Precambrian time. We propose that stronger cell adhesion allowed the integrity of genetically uniform animals composed only of "self" cells, facilitating genetic constitutions to remain within the metazoan individual and be passed down inheritance lines. The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self-/non-self-recognition and of a surge in seawater calcium that increased the binding forces between their calcium-dependent cell adhesion molecules.

JTD Keywords: Calcium, Cambrian explosion, Carbohydrates, Cell adhesion, Origin of Metazoa, Sponges

In the past years, the quartz crystal microbalance (QCM) has been successfully applied to follow interfacial physical chemistry phenomena in a label free and real time manner. However, carbohydrate self adhesion has only been addressed partially using this technique. Carbohydrates play an important role in cell adhesion, providing a highly versatile form of attachment, suitable for biologically relevant recognition events in the initial steps of adhesion. Here, we provide a QCM study of carbohydrates' self-recognition in the presence of calcium, based on a species-specific cell recognition model provided by marine sponges. Our results show a difference in adhesion kinetics when varying either the calcium concentration (with a constant carbohydrate concentration) or the carbohydrate concentration (with constant calcium concentration).

JTD Keywords: Biomedical materials, Calcium, Cellular biophysics, Microbalances, Porous materials, Quartz, Surface chemistry/ bio-QCM, Carbohydrates self-interaction, Quartz crystal microbalance, Interfacial physical chemistry phenomena, Carbohydrate self adhesion, Biologically relevant recognition events, Marine sponges, Adhesion kinetics, Calcium concentration, Carbohydrate concentration, Biosensors, Biomedical materials, Surface chemistry, Cellular biophysics