Unveiling the Function of the Mitochondrial Filament-Forming Protein LACTB in Lipid Metabolism and Cancer

LACTB is a relatively unknown mitochondrial protein structurally related to the bacterial penicillin-binding and beta-lactamase superfamily of serine proteases. LACTB has recently gained an increased interest due to its potential role in lipid metabolism and tumorigenesis. To date, around ninety studies pertaining to LACTB have been published, but the exact biochemical and cell biological function of LACTB still remain elusive. In this review, we summarise the current knowledge about LACTB with particular attention to the implications of the recently published study on the cryo-electron microscopy structure of the filamentous form of LACTB. From this and other studies, several specific properties of LACTB emerge, suggesting that the protein has distinct functions in different physiological settings. Resolving these issues by further research may ultimately lead to a unified model of LACTB’s function in cell and organismal physiology. LACTB is the only member of its protein family in higher animals and LACTB may, therefore, be of particular interest for future drug targeting initiatives

Unveiling the Function of the Mitochondrial Filament-Forming Protein LACTB in Lipid Metabolism and Cancer

LACTB is a relatively unknown mitochondrial protein structurally related to the bacterial penicillin-binding and beta-lactamase superfamily of serine proteases. LACTB has recently gained an increased interest due to its potential role in lipid metabolism and tumorigenesis. To date, around ninety studies pertaining to LACTB have been published, but the exact biochemical and cell biological function of LACTB still remain elusive. In this review, we summarise the current knowledge about LACTB with particular attention to the implications of the recently published study on the cryo-electron microscopy structure of the filamentous form of LACTB. From this and other studies, several specific properties of LACTB emerge, suggesting that the protein has distinct functions in different physiological settings. Resolving these issues by further research may ultimately lead to a unified model of LACTB’s function in cell and organismal physiology. LACTB is the only member of its protein family in higher animals and LACTB may, therefore, be of particular interest for future drug targeting initiatives

Destabilization of the Outer and Inner Mitochondrial Membranes by Core and Linker Histones

Peer reviewe

c-Abl Inhibitors Enable Insights into the Pathophysiology and Neuroprotection in Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder causing movement disabilities and several non-motor symptoms in afflicted patients. Recent studies in animal models of PD and analyses of brain specimen from PD patients revealed an increase in the level and activity of the non-receptor tyrosine kinase Abelson (c-Abl) in dopaminergic neurons with phosphorylation of protein substrates, such as alpha-synuclein and the E3 ubiquitin ligase, Parkin. Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia have shown promising neuroprotective effects in cell and animal models of PD. This has raised hope that similar beneficial outcome may also be observed in the treatment of PD patients by using c-Abl inhibitors. Here we highlight the background for the current optimism, reviewing c-Abl and its relationship to pathophysiological pathways prevailing in PD, as well as discussing issues related to the pharmacology and safety of current c-Abl inhibitors. Clearly more rigorously controlled and well-designed trials are needed before the c-Abl inhibitors can be used in the neuroclinic to possibly benefit an increasing number of PD patients.Peer reviewe

Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration - A Mass Spectrometry Imaging Study of the Perfused Rat Liver

Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition. MALDI mass spectra of thin-sections of freeze-clamped rat liver perfused with metformin showed a peak at 130.16 m/z which was unambiguously assigned to metformin. The mass spectrometric detection limit was at a tissue concentration of about 250 nM, and uptake of metformin from the perfusion medium to the liver occurred with a K-m of 0.44 mM. Metformin was evenly distributed in the liver irrespective of its concentration in the perfusion medium and the duration of a perfusion. At a parenchymal concentration of 30 mu M, metformin did not induce any significant suppression of the basal or lactate-induced glucose release from the liver. These results show that matrix-assisted laser desorption/ionization mass spectrometry imaging can be applied to estimate the tissue concentration and distribution of metformin in a therapeutically relevant micromolar concentration range. Our findings challenge the view that metformin causes an inhibition of glucose release from the liver by an acute inhibition of mitochondrial glycerol 3-phosphate dehydrogenase (EC 1.1.5.3).Peer reviewe

Study and Prevention of Lipid Oxidation in Meat

In according to the importance of meat in the diet and of its diffuse use in Western Countries, it’s necessary to give attention to a particular nutritional aspect of meat, concerning food safety, which is one of the most important goals in food science nowadays. It is well know that PUFA fatty acid and iron are among main factors improving lipid oxidation, so their reduction by animal diet may be an efficacy mean to improve oxidative stability in meat. However, this measure may not be acceptable in practice because PUFA and iron are both nutritional elements for human health. This research work has begun from studying of antioxidant to prevent lipid oxidation until arriving to find a model to induce oxidation to investigate the process in vitro. Work plan can be schedules in three parts: Part 1: protective effects of natural antioxidants against peroxidation during cooking and storage Part 2: Determination of MDA and TBARs in Buffalo Meat from Animals with dietary supplementation of Vitamin E Part 3: Development of analytical procedures to study changes in the lipid composition of meat caused by induced oxidation

Road traffic Modelling and Simulating with fluid-dynamic approach

In this work we present a mathematical model for fluid-dynamic flows on road networks, based on conservation laws according with Piccoli et al. approach. The road network is represented by means of a links and nodes structure. A description of Riemann Solver at junction is given and a complete implementation of this model is then presented, together with some results from computational experiences on different real case studies of road networks