Dysregulated Lipid Metabolism and Its Role in α-Synucleinopathy in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease, the main pathological hallmark of which is the accumulation of α-synuclein (α-syn) and the formation of filamentous aggregates called Lewy bodies in the brainstem, limbic system, and cortical areas. Lipidomics is a newly emerging field which can provide fresh insights and new answers that will enhance our capacity for early diagnosis, tracking disease progression, predicting critical endpoints, and identifying risk in pre-symptomatic persons. In recent years, lipids have been implicated in many aspects of PD pathology. Biophysical and lipidomic studies have demonstrated that α-syn binds preferentially not only to specific lipid families but also to specific molecular species and that these lipid-protein complexes enhance its interaction with synaptic membranes, influence its oligomerization and aggregation, and interfere with the catalytic activity of cytoplasmic lipid enzymes and lysosomal lipases, thereby affecting lipid metabolism. The genetic link between aberrant lipid metabolism and PD is even more direct, with mutations in GBA and SMPD1 enhancing PD risk in humans and loss of GALC function increasing α-syn aggregation and accumulation in experimental murine models. Moreover, a number of lipidomic studies have reported PD-specific lipid alterations in both patient brains and plasma, including alterations in the lipid composition of lipid rafts in the frontal cortex. A further aspect of lipid dysregulation promoting PD pathogenesis is oxidative stress and inflammation, with proinflammatory lipid mediators such as platelet activating factors (PAFs) playing key roles in arbitrating the progressive neurodegeneration seen in PD linked to α-syn intracellular trafficking. Lastly, there are a number of genetic risk factors of PD which are involved in normal lipid metabolism and function. Genes such as PLA2G6 and SCARB2, which are involved in glycerophospholipid and sphingolipid metabolism either directly or indirectly are associated with risk of PD. This review seeks to describe these facets of metabolic lipid dysregulation as they relate to PD pathology and potential pathomechanisms involved in disease progression, while highlighting incongruous findings and gaps in knowledge that necessitate further research

Organic farming, a viable and feasible component of the Romanian agriculture

Taking into account the fact that organic farming is not a miracle, but a tangible reality of our days, a trend with more and more followers within the producers and consumers, this paper is included within those trying to demonstrate once more that for Romania also, the organic farming is a viable alternative to the traditional farming that leads in time to the degradation of soil and water resources, to air pollution, degradation of population heath etc. By using as working method the direct observation without intervention and consulting specialized reference sources, we have tried to select the most important definitions for the Romanian organic farming. We have also specified the objectives and principles of the organic farming and we have made a selection of the most important legal regulations on which the environment-friendly production is based, both at Community level and at national level. The analysis of the organic farming in Romania also showed that a process of institutional strengthening and development is currently undergoing for the organic farming, as in all the other countries, and the Ministry of Agriculture and Rural Development, by its actions, puts the organic farming in the centre of the development of the Romanian agriculture. As such, the evolution of this sector from one year to another was dynamic, with a steady pace growth of the eco-cultivated areas and of the number of animals resulted from organic livestock breeding. The analysis performed entitles us to consider that the organic farming is an inadequately capitalized opportunity for Romania that could place the country as a front-runner on the European market

Organic farming, a viable and feasible component of the Romanian agriculture

Taking into account the fact that organic farming is not a miracle, but a tangible reality of our days, a trend with more and more followers within the producers and consumers, this paper is included within those trying to demonstrate once more that for Romania also, the organic farming is a viable alternative to the traditional farming that leads in time to the degradation of soil and water resources, to air pollution, degradation of population heath etc. By using as working method the direct observation without intervention and consulting specialized reference sources, we have tried to select the most important definitions for the Romanian organic farming. We have also specified the objectives and principles of the organic farming and we have made a selection of the most important legal regulations on which the environment-friendly production is based, both at Community level and at national level. The analysis of the organic farming in Romania also showed that a process of institutional strengthening and development is currently undergoing for the organic farming, as in all the other countries, and the Ministry of Agriculture and Rural Development, by its actions, puts the organic farming in the centre of the development of the Romanian agriculture. As such, the evolution of this sector from one year to another was dynamic, with a steady pace growth of the eco-cultivated areas and of the number of animals resulted from organic livestock breeding. The analysis performed entitles us to consider that the organic farming is an inadequately capitalized opportunity for Romania that could place the country as a front-runner on the European market

Altered sphingoid base profiles in type 1 compared to type 2 diabetes

Background: Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. Findings: We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 1-deoxySLs were significantly higher in the groups with T2DM but not different between T1DM and controls. In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. Conclusions: Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. Electronic supplementary material The online version of this article (doi:10.1186/1476-511X-13-161) contains supplementary material, which is available to authorized users

Developments in the European market of organic agricultural products

This paper represents an analysis of the development of the European organic agricultural product market, taking into account especially the consumption of organic agricultural products and some aspects regarding the consumers’ behaviour. The period between 2000 and 2012 was analysed, with particular attention to the situation existent in 2012 and with references to the global situation. The tendencies that are foreseen for the future of this market segment are also considered. The conclusions of this analysis emphasize the idea that, in an era when the population is increasingly more informed and interested in its health and of the environment it is living in, the organic food market, which is still a niche market, has real opportunities of development. The only condition is that all of those involved in this sector of organic farming (producers, processors and retailers) join forces in order to develop concepts and strategies for the organic farming of the future

Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury

Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects. DILI patients, whether intrinsic or idiosyncratic cases, had no alterations in total sphingoid base levels and profile composition compared to controls, whereby cardiovascular disease (CVD) was a confounding factor. Upon exclusion of CVD individuals, elevation of 1-deoxysphingosine (1-deoxySO) in the DILI group emerged. Notably, 1-deoxySO values did not correlate with ALT values. While 1-deoxySO was elevated in all DILI cases, only intrinsic DILI cases concomitantly displayed reduction of select shorter chain sphingoid bases. Significant perturbation of the sphingolipid metabolism observed in this small exploratory clinical study is discussed and put into context, in the consideration that sphingolipids might contribute to the onset and progression of DILI, and that circulating sphingoid bases may function as mechanistic markers to study DILI pathophysiology

Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury

Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects. DILI patients, whether intrinsic or idiosyncratic cases, had no alterations in total sphingoid base levels and profile composition compared to controls, whereby cardiovascular disease (CVD) was a confounding factor. Upon exclusion of CVD individuals, elevation of 1-deoxysphingosine (1-deoxySO) in the DILI group emerged. Notably, 1-deoxySO values did not correlate with ALT values. While 1-deoxySO was elevated in all DILI cases, only intrinsic DILI cases concomitantly displayed reduction of select shorter chain sphingoid bases. Significant perturbation of the sphingolipid metabolism observed in this small exploratory clinical study is discussed and put into context, in the consideration that sphingolipids might contribute to the onset and progression of DILI, and that circulating sphingoid bases may function as mechanistic markers to study DILI pathophysiology

Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway

The 1-deoxysphingolipids (1-deoxySLs) are atypical sphingolipids (SLs) that are formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during SL synthesis. The 1-deoxySLs are toxic to neurons and pancreatic β-cells. Pathologically elevated 1-deoxySLs cause the inherited neuropathy, hereditary sensory autonomic neuropathy type 1 (HSAN1), and are also found in T2D. Diabetic sensory polyneuropathy (DSN) and HSAN1 are clinically very similar, suggesting that 1-deoxySLs may be implicated in both pathologies. The 1-deoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl group, which is essential for the canonical degradation of SLs. Here, we report a previously unknown metabolic pathway, which is capable of degrading 1-deoxySLs. Using a variety of metabolic labeling approaches and high-resolution high-accuracy MS, we identified eight 1-deoxySL downstream metabolites, which appear to be formed by cytochrome P450 (CYP)4F enzymes. Comprehensive inhibition and induction of CYP4F enzymes blocked and stimulated, respectively, the formation of the downstream metabolites. Consequently, CYP4F enzymes might be novel therapeutic targets for the treatment of HSAN1 and DSN, as well as for the prevention of T2D

The Impact of Facebook Upon Social Skills of Young People ‒ a Business Employment Perspective

Social networks can be successfully used to promote any business, being developed in such a way to allow both individuals and business organizations to interact one with another. Companies may obtain important information about users of social networks which will help to a better understanding of their profile and needs and, consequently, to build their marketing and sales strategies. According to the latest data, Facebook is the most popular social network, with the highest number of registered users from all over the world. The current paper aims to determine the way Facebook users – and more precisely young students belonging to Romanian economic field, behave in respect to this social network from the point of view of information valuable for businesses. The findings of the paper are based on a survey deployed in 2014 and they reveal that although the time spent for online social interaction with friends is longer than the time spent for face to face discussions, users’ social skills needed for their future employment do not seem affected