Dissecting the effects of free fatty acids on the thermodynamic stability of complex model membranes mimicking insulin secretory granules

A stepwise micro-DSC study of Small, Large and Giant Unilamellar Vesicles prepared as pure and mixed systems of DMPC, DPPC, DSPC and DOPC was performed, achieving the preparation of final model membranes whose phospholipid compositions represent the 75% in terms of the phospholipids tails and the 50% headgroups of the Insulin Secretory Granules (vesicles located in the pancreatic Langerhans \u3b2-cells and which are responsible for insulin and amylin storage and secretion in response to nutrient intake). Moreover, the effect of Free Fatty Acids, whose levels are recurrently altered in diabetic and/or obese subjects, on the thermodynamic stability of the final membranes was eventually investigated. The results allowed to discriminate each single thermodynamic contribution among the main factors that dictate the overall thermodynamic stability of these complex unilamellar systems evidencing mainly entropic effects hierarchically summarized as phospholipid unsaturations > phospholipid tail length > membrane curvature. The effect of the Free Fatty Acids highlighted a strong stabilizing effect on the membranes as well as more pronounced phase segregations in the case of saturated acids (palmitic and stearic), whereas the opposite effect was observed in the case of an unsaturated one (oleic)

Solving the Problem of Organ Donation Shortage

Organ donation, a medically perfected procedure, affords a second chance at life for many people. Unfortunately, organ transplantation demonstrates the stark reality of supply and demand. Thousands of individuals are added to the transplant list each day, but many more die during the same time frame waiting for new organs. The solution to this dilemma seems simple: increase the supply. This article will discuss several ways to achieve this goal. First, through the HIV Organ Policy Equity Act, which allows for HIV-positive-to-HIV-positive transplants, more transplantable organs will hopefully be available in the future. Second, the supply of organs may increase by changing the standards of organ donation from irreversible loss of brain function to irreversible loss of cardiac function. Third, educating individuals, especially minorities, about donation and the regionally based system for transplants may result in a larger number of matching donors and a greater number of potential recipients on multiple transplant lists. Finally, efforts such as payments and advertising for organs, giving priority transplants to registered donors, and even confronting the disparate number of elderly donors whose organs are never transplanted, may result in an increase in the organ supply

Solving the Problem of Organ Donation Shortage

Organ donation, a medically perfected procedure, affords a second chance at life for many people. Unfortunately, organ transplantation demonstrates the stark reality of supply and demand. Thousands of individuals are added to the transplant list each day, but many more die during the same time frame waiting for new organs. The solution to this dilemma seems simple: increase the supply. This article will discuss several ways to achieve this goal. First, through the HIV Organ Policy Equity Act, which allows for HIV-positive-to-HIV-positive transplants, more transplantable organs will hopefully be available in the future. Second, the supply of organs may increase by changing the standards of organ donation from irreversible loss of brain function to irreversible loss of cardiac function. Third, educating individuals, especially minorities, about donation and the regionally based system for transplants may result in a larger number of matching donors and a greater number of potential recipients on multiple transplant lists. Finally, efforts such as payments and advertising for organs, giving priority transplants to registered donors, and even confronting the disparate number of elderly donors whose organs are never transplanted, may result in an increase in the organ supply

Metabolic risk of new food technologies: calorimetric study of model cell membranes for the determination of the influence of free fatty acids (FFA) in diabetes mellitus onset

Type 2 diabetes mellitus (T2DM) is a chronic disease that continues to spread in both developed and developing countries. Indeed, the individuals affected by diabetes mellitus (type 1 and type 2) in the world are now close to 400 million and estimates suggest that they will reach 600 million by 2035. The rapid spreading of this disorder is influenced not only by genetic factors but also by environmental ones: socio-economic variations, evolution of lifestyle and changes in dietary habits have contributed to increase the percentage of overweight and obese individuals, which in turn have led to a greater diffusion of diabetes. In fact, weight gain is closely related to insulin-resistance onset, which is considered as the starting point for the development of the disease. However, the manner in which obesity and nutrition factors are linked to the onset of T2DM is not fully understood yet, especially at a molecular level. The aim of the project presented here is to prepare and characterize (thermodynamically and spectroscopically) model membranes which simulate as possible the phospholipid bilayers of the Langerhans \u3b2-cells in order to highlight and discriminate the role of the lipid composition and foodborne stress (in terms of [Ca2+] and [FFA]) in the membrane stability. Moreover, the interaction between the model membrane and hIAPP, which seems to be involved in \u3b2-cells death, will be used to evaluate the influence of membrane stability on T2DM onset

Thermodynamic stability of complex model membranes: the role of composition, morphology and food fatty acids

Free Fatty Acids (FFAs) have been shown to be involved in several membrane-mediated cellular processes as lipid-assisted protein transport across the bilayer, fusion of lipid vesicles/cells and signalling for several cell mechanisms (e.g. insulin secretion). However, altered plasma FFAs levels typical of obese and/or diabetic subjects have been proposed to contribute to the onset and progression of type 2 diabetes mellitus through both their possible involvement in altered metabolic pathways and their direct action on cell membranes. Moreover, the action of FFAs has also been hypothesized to play a role in the interaction of amylin, an amyloidogenic protein, with cell membranes likely leading to the pancreatic \u3b2-cells failure by apoptosis. Among several studies highlighting the FFAs-membrane interaction by means of spectroscopic, imaging, molecular dynamics and/or theoretical approaches, few works are devoted to a thermodynamic characterization of the role of FFAs on the overall membrane stability, however without considering the compositional and morphological complexity of real biological vesicles. In such a frame, the present work was aimed at the calorimetric investigation of small, large and giant unilamellar vesicles prepared as pure and mixed systems of phospholipids with different length and unsaturation level. The preparation of a final model membrane was finally achieved mimicking the phospholipid bilayer of Insulin Secretory Granules (ISGs), vesicles located in the pancreatic Langerhans \u3b2-cells and which are responsible for insulin and amylin storage and secretion in response to nutrients intake. This study was performed through micro-DSC and allowed to discriminate each single thermodynamic contribution among the main factors that dictate the overall thermodynamic stability of these complex unilamellar systems (phospholipid unsaturations > phospholipid tail length > membrane curvature). The effect of three different FFAs, such as palmitic, stearic and oleic acids, added in different percentages both to a completely saturated ternary model membrane and to an unsaturated one (i.e. the final model membrane made by the saturated one including the 5% of 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) was eventually investigated highlighting a strong stabilizing effect as well as more pronounced phase segregations in the case of saturated acids, whereas the opposite effect was observed in the case of unsaturated FFAs. Moreover, the stabilizing effects deriving from saturated FFAs were more pronounced in less stable membranes, i.e. the unsaturated one, whereas the destabilizing effects deriving from the unsaturated FFAs were more pronounced in more stable membranes, i.e. the completely saturated one

The DSC monitoring of oil melting to follow the oil curing

The drying of an oil paint is due to the polyunsaturations of the oil in the binder. Polyunsaturated oils dry trough an autoxidation process in which the double bonds of linolenic and linoleic acids naturally react with the oxygen present in the atmosphere. The gradual conversion of the liquid oil through a soft gel to a rubbery solid occurs as a result of a multistep free radical chain reaction. During the propagation step, hydroperoxides are formed. A method frequently used to follow the oil curing is the DSC monitoring of the peroxide decomposition peak during time. Since the oil polymerization affects its crystallinity, we propose here an altemative method to asses the oil curing. The melting peak of linseed oil samples is measured at different times of curing and compared with the pro\ufb01le of the peroxide decomposition peak over time. The comparison shows that the two phenomena are strongly correlated and that, when the maximum of the peroxide content is reached, the melting peak disappears. The study of the DSC melting peak is therefore proposed as a valid alternative tool to monitor the curing of an oil paint

Midterm Outcomes of the Nellix Endovascular Aneurysm Sealing System: A Dual-Center Experience

Purpose: To report midterm outcomes of the Nellix Endovascular Aneurysm Sealing (EVAS) System in the treatment of abdominal aortic aneurysm (AAA). Methods: Between September 2013 and July 2014, 64 AAA patients (mean age 76.6±6.8 years; 61 men) were treated with the EVAS system at 2 centers (only procedures performed at least 12 months prior to the analysis were included). Most patients were treated for a stable AAA, while 1 patient was treated for a ruptured aneurysm. Mean aneurysm diameter was 57.3±9.3 mm. The proximal neck measured a mean 21.5±3.3 mm in diameter and 27.0±12.1 mm long; the neck angle was 16.9°±19.3°. Eleven (17.2%) patients were treated outside the instructions for use (IFU). Results: Technical success was achieved in 63 (98.4%) of 64 patients; 1 type Ia endoleak was treated intraoperatively. One (1.6%) aneurysm-related death occurred at 4 months due to a secondary aortoenteric fistula. Overall, endoleaks occurred in 3 (4.7%) patients (2 type Ia, 1 type II). The estimated rates for 18-month overall survival, freedom from aneurysm-related death, and freedom from secondary interventions were 92.7%, 98.4%, and 95.0%, respectively. Patients treated outside the IFU had a significantly higher incidence of device-related complications (p=0.03). Conclusion: The use of the Nellix device in everyday clinical practice is safe and offers promising midterm results. The risk of secondary aortoenteric fistula requires further analysis. Longer follow-up is needed to assess the actual efficacy of the device, although the risk of migration with late endoleak seems low

Knotlike Cosmic Strings in The Early Universe

In this paper, the knotlike cosmic strings in the Riemann-Cartan space-time of the early universe are discussed. It has been revealed that the cosmic strings can just originate from the zero points of the complex scalar quintessence field. In these strings we mainly study the knotlike configurations. Based on the integral of Chern-Simons 3-form a topological invariant for knotlike cosmic strings is constructed, and it is shown that this invariant is just the total sum of all the self-linking and linking numbers of the knots family. Furthermore, it is also pointed out that this invariant is preserved in the branch processes during the evolution of cosmic strings