A simple electronic ladder model harboring Z4\mathbb{Z}_4 parafermions

Parafermions are anyons with the potential for realizing non-local qubits that are resilient to local perturbations. Compared to Majorana zero modes, braiding of parafermions implements an extended set of topologically protected quantum gates. This, however, comes at the price that parafermionic zero modes can not be realized in the absence of strong interactions whose theoretical description is challenging. In the present work, we construct a simple lattice model for interacting spinful electrons with parafermionic zero energy modes. The explicit microscopic nature of the considered model highlights new realization avenues for these exotic excitations in recently fabricated quantum dot arrays. By density matrix renormalization group calculations, we identify a broad range of parameters, with well-localized zero modes, whose parafermionic nature is substantiated by their unique $8\pi$ periodic Josephson spectrum

Fructose, glucocorticoids and adipose tissue: Implications for the metabolic syndrome

The modern Western society lifestyle is characterized by a hyperenergetic, high sugar containing food intake. Sugar intake increased dramatically during the last few decades, due to the excessive consumption of high-sugar drinks and high-fructose corn syrup. Current evidence suggests that high fructose intake when combined with overeating and adiposity promotes adverse metabolic health effects including dyslipidemia, insulin resistance, type II diabetes, and inflammation. Similarly, elevated glucocorticoid levels, especially the enhanced generation of active glucocorticoids in the adipose tissue due to increased 11β-hydroxysteroid dehydrogenase 1 (11β -HSD1) activity, have been associated with metabolic diseases. Moreover, recent evidence suggests that fructose stimulates the 11β -HSD1-mediated glucocorticoid activation by enhancing the availability of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11β -HSD1 expression and activity, thereby promoting the adipogenic effects of glucocorticoids. This article aims to highlight the interconnections between overwhelmed fructose metabolism, intracellular glucocorticoid activation in adipose tissue, and their metabolic effects on the progression of the metabolic syndrome. © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

On the role of 4-hydroxynonenal in health and disease

AbstractPolyunsaturated fatty acids are susceptible to peroxidation and they yield various degradation products, including the main α,β-unsaturated hydroxyalkenal, 4-hydroxy-2,3-trans-nonenal (HNE) in oxidative stress. Due to its high reactivity, HNE interacts with various macromolecules of the cell, and this general toxicity clearly contributes to a wide variety of pathological conditions. In addition, growing evidence suggests a more specific function of HNE in electrophilic signaling as a second messenger of oxidative/electrophilic stress. It can induce antioxidant defense mechanisms to restrain its own production and to enhance the cellular protection against oxidative stress. Moreover, HNE-mediated signaling can largely influence the fate of the cell through modulating major cellular processes, such as autophagy, proliferation and apoptosis. This review focuses on the molecular mechanisms underlying the signaling and regulatory functions of HNE. The role of HNE in the pathophysiology of cancer, cardiovascular and neurodegenerative diseases is also discussed

Fructose promotes the differentiation of 3T3-L1 adipocytes and accelerates lipid metabolism

Excessive fructose consumption and elevated glucocorticoids contribute to metabolic syndrome. We show that fructose as the only carbohydrate source is sufficient for the differentiation of 3T3-L1 fibroblasts into adipocytes. Differentiation of cells in fructose containing medium resulted in increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression and activity. Experiments with transfected HEK-293 cells suggested more efficient NADPH generation by fructose compared with glucose in the endoplasmic reticulum (ER). Adipocytes differentiated in the presence of fructose showed increased FABP4 expression, C/EBPα to C/EBPβ ratio and lipolysis. Thus, excessive fructose may cause adverse metabolic effects by enhancing 11β-HSD1 activity and increasing lipolysis in adipocytes

Aortoiliacalis stenoocclusiv betegség fedett sztentekkel végzett endovascularis ellátásával szerzett kezdeti tapasztalataink

Bevezetés: A komplex aortoiliacalis stenoocclusiv betegségek kezelésének megoldását hagyományosan a nyitott műtéti technikák jelentik. Napjainkban azonban a kisebb perioperatív megterheléssel járó endovascularis vagy hibrid beavatkozások – mint például a fedettsztent-implantáció – is megoldásként szolgálhatnak, amelyekkel akár aortobiilia- calis, akár aortobifemoralis áthidalások kiválthatók. Célkitűzés: A vascularis centrumunkban végzett ortoiliacalis fedett sztent implantációk korai eredményeinek elemzése. Módszer: A 2019. november 1. és 2021. szeptember 30. között prospektíven regisztrált, konszekutív, aortoiliacalis fedett sztent implantációján átesett betegek adatainak retrospektív elemzését végeztük. Rögzítettük a betegek de- mográfiai és preoperatív egészségügyi adatait, a perioperatív szövődményeket, emellett a pre- és posztoperatívan megállapított Rutherford-stádiumot és boka-kar indexet. Vizsgálatunk elsődleges végpontja a perioperatív mortalitás, illetve az egyéves túlélés és elsődleges nyitva maradás, míg másodlagos végpontja a boka-kar index, illetve a Rutherford-stádium változásának és az amputációs rátának a megállapítása volt. Elemzésünkhöz Kaplan–Meier-analízist és Wilcoxon-féle ’signed-ranked’ tesztet használtunk. Eredmények: Vizsgálatunkba 36 beteget vontunk be. Az átlagos utánkövetési idő 12 ± 6,9 hónap volt. 72,2%-ban (n = 26) TASC C–D klasszifikációjú aortoiliacalis elváltozás miatt végeztünk beavatkozást, 44%-ban (n = 16) kritikus alsó végtagi ischaemia miatt, 64%-ban (n = 23) percutan punkcióból. A kórházban töltött napok száma átlagosan 5 ± 7 nap volt. Perioperatív vérzéses szövődmény 4 (11,1%), reoperáció 6 (16,6%) esetben fordult elő. Perioperatív halálozás nem történt. Az egyéves túlélés 94,3%, az elsődleges nyitva maradás 91,4% volt. A betegek posztoperatív Rutherford-stádiuma (3. [2.] vs. 1. [1.]; p<0,001) és boka-kar indexe (0,4 [0,55] vs. 1 [0,4]; p<0,001) szignifikánsan javult a preoperatívhoz képest. Nem tervezett major amputációt nem végeztünk. Következtetés: Az aortoiliacalis stenoocclusiv betegségek kezelésében fedett sztentek használatával jelentős klinikai javulás mellett kedvező perioperatív mortalitás, egyéves túlélés és elsődleges nyitva maradás, illetve elfogadható perioperatív morbiditás érhető el. Ez az eljárás megfelelő alternatívája lehet a nyitott műtéti megoldásoknak

Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes

The present study demonstrates the expression of hexose-6-phosphate dehydrogenase and 11 beta-hydroxysteroid dehydrogenase type 1 in human neutrophils, and the presence and activity of these enzymes in the microsomal fraction of the cells. Their concerted action together with the previously described glucose-6-phosphate transporter is responsible for cortisone-cortisol interconversion detected in human neutrophils. Furthermore, the results suggest that luminal NADPH generation by the cortisol dehydrogenase activity of 11 beta-hydroxysteroid dehydrogenase type 1 prevents neutrophil apoptosis provoked by the inhibition of the glucose-6-phosphate transporter. In conclusion, the maintenance of the luminal NADPH pool is an important antiapoptotic factor in neutrophil granulocytes

Metabolic stability of cells for extended metabolomical measurements using NMR. A comparison between lysed and additionally heat inactivated cells.

NMR measurements for metabolic characterization of biological samples like cells, biopsies or plasma, may take several hours for advanced methods. Preanalytical issues, such as sample preparation and stability over the measurement time, may have a high impact on metabolite content, and potentially lead to misinterpretation. The aim of this study was therefore to investigate by 1H HR-MAS NMR the impact of different cell handling preparation protocols on the stability of the cell metabolite content over the measurement time. For this purpose, the metabolite content of fibroblasts and adrenal cells were measured at different time points after lysis and after additional heating. Interestingly the results showed similar metabolite concentrations between lysed and lysed-heated cells at the beginning of the measurement, but increasing differences after some hours of measurement. In lysed cells, metabolism was ongoing, producing metabolite changes over time, contrary to a stable metabolite content of the lysed-heated cells. These results were confirmed in both fibroblasts and adrenal cells. Therefore, in order to minimize metabolite content modifications over the measurement time, it is suggested to use cell lysis in combination with heat inactivation for extended HR-MAS NMR measurements

Contribution of fructose-6-phosphate to glucocorticoid activation in the endoplasmic reticulum : possible implication in the metabolic syndrome

Both fructose consumption and increased intracellular glucocorticoid activation have been implicated in the pathogenesis of the metabolic syndrome. Glucocorticoid activation by 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) depends on hexose-6-phosphate dehydrogenase (H6PD), which physically interacts with 11?-HSD1 at the luminal surface of the endoplasmic reticulum (ER) membrane and generates reduced nicotinamide adenine dinucleotide phosphate for the reduction of glucocorticoids. The reducing equivalents for the reaction are provided by glucose-6-phosphate (G6P) that is transported by G6P translocase into the ER. Here, we show that fructose-6-phosphate (F6P) can substitute for G6P and is sufficient to maintain reductase activity of 11?-HSD1 in isolated microsomes. Our findings indicate that the mechanisms of F6P and G6P transport across the ER membrane are distinct and provide evidence that F6P is converted to G6P in the ER lumen, thus yielding substrate for H6PD-dependent reduced nicotinamide adenine dinucleotide phosphate generation. Using the purified enzyme, we show that F6P cannot be directly dehydrogenated by H6PD, and we also excluded H6PD as a phosphohexose isomerase. Therefore, we postulate the existence of an ER luminal hexose-phosphate isomerase different from the cytosolic enzyme. The results suggest that cytosolic F6P promotes prereceptor glucocorticoid activation in white adipose tissue, which might have a role in the pathophysiology of the metabolic syndrome