• Energy Research
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• University of Göttingen close

Ethanol exerts its behavioural effects largely by interacting with receptors for brain neurotransmitters. However, the molecular mechanisms involving these interactions and the pathogenesis of alcohol-withdrawal symptomatology are still not well understood. Until recently, no data were available about homocysteine (Hcy) levels in acute alcohol intoxication of chronic alcoholics and in patients undergoing withdrawal from alcohol. Hcy, blood-alcohol concentrations, vitamins B6, B12, and folate concentrations were assessed in 29 chronic alcoholics, who underwent withdrawal from alcohol. We observed increased Hcy levels in most patients. Hcy levels steadily decreased during the observation period. We postulate that hyperhomocysteinaemia and excitatory amino acid neurotransmitters, by their agonism at the N-methyl-D-aspartate receptor, may partly mediate alcohol-associated withdrawal symptomatology. The importance of assessing serum Hcy levels in order to detect methylation deficiency in patients with chronic alcoholism and for possible therapeutic strategies is discussed.

The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (P<0. 01) between blood alcohol concentration and elevated homocysteine (Spearman's r=0.71) and malondialdehyde (r=0.90) levels on admission. In addition, homocysteine and malondialdehyde levels were found to be significant decreased after 3 days of withdrawal treatment (Wilcoxon test: homocysteine, Z=-5.127; malondialdehyde, Z=-3.120; P<0.01). We postulate that excitatory neurotransmitters and mechanisms of oxidative stress in patients with chronic alcoholism may partly mediate excitotoxic neuronal damage and hereby cause brain shrinkage.

Liver carbohydrate metabolism and blood flow are regulated by hepatic nerves and hormones such as glucagon, insulin or catecholamines. Acute and chronic application of alcohol are known to depress the function of central and peripheral nerves. The extent of inhibition of the autonomic nervous system is not well characterized; thus, the possible impairment of hepatic nerve function by acute and chronic application of ethanol was investigated.Rat livers were perfused simultaneously via both the portal vein and hepatic artery. Hepatic nerves were stimulated electrically for 2 min (20 Hz, 20 V, 2 ms). As a control, noradrenaline (1 microM) was infused into the portal vein for 2 minutes.During acute application of ethanol in portal concentrations of 50, 150 and 300 mM, which elevated basal glucose release, stimulation of hepatic nerves as well as portal noradrenaline infusion caused the same increase in glucose output and decrease in portal and arterial flow as in controls. Following chronic application of ethanol by feeding rats the Lieber-DeCarli liquid diet containing 5% (v/v) ethanol for 4 and 6 weeks, only nerve stimulation caused a significantly reduced enhancement of glucose output (50%, p < 0.025), whereas portal noradrenaline was as effective as in controls. Noradrenaline overflow was significantly reduced following nerve stimulation.The decrease in nerve stimulation-dependent glucose output and noradrenaline overflow in chronically ethanol fed rats indicates an impaired function of hepatic nerves.

The middle class in India is estimated to be roughly half of the population and, as such, holds considerable sway in influencing consumption trends. We explored food consumption practices and indicators for food transitions among middle-class households in the South Indian megacity of Bengaluru. Through 38 qualitative interviews, we asked respondents about their perceptions of food safety and how they navigate food safety risks in their daily food practices. The COVID-19 pandemic brought the topic of food safety into sharp relief, and consumers were keen on maintaining good health through food consumption. We engaged social practice theory to understand food shopping practices, the rise in immune-boosting foods and the consumer demand for safe, healthy food as this relates to wider sustainable food transitions. We found that middle-class consumers mitigate food safety risks through careful selection of where food is purchased. A rise in immune-boosting foods, traditional herbs and spices part of the regional diet are being revitalized. Demand for organically grown foods is hampered by a lack of trust in verification systems. We argued that government investment in building consumer confidence in both food safety, and organic labeling increases the willingness to pay a premium price among middle-class consumers.

Increased drought combined with emerging pathogens poses an increased threat to forest health. This is attributable to the unpredictable behaviour of forest pathosystems, which can favour fungal pathogens over the host under persistent drought stress conditions. Diplodia sapinea (≡ Sphaeropsis sapinea) is one of the most severe pathogens in Scots pine (Pinus sylvestris) causing Diplodia tip blight (conifer blight) under certain environmental conditions. Recently, the fungus has also been isolated from non-conifer hosts, indicating that it has a broader host range than previously known. In this study we compared the impact of different levels of water availability on necrosis length caused by D. sapinea strains isolated as endophytes (eight strains isolated from asymptomatic Scots pine) and pathogens (five strains isolated from symptomatic Scots pine) and five strains isolated from symptomatic non-pine hosts. For all strains the decreased water availability increased the necrosis length in Scots pine shoots. The isolates from non-pine hosts caused the most severe reactions under all water availabilities. The results of the study indicate the likelihood that effects of climatic changes such as drought will drive D. sapinea damage in Scots pine-dominated forests and increase mortality rates in affected trees. Further, the higher necrosis in the Scots pines caused by strains that had performed a host switch are concerning with regard to future scenarios thus increasing infection pressure on Scots pine from unknown sources.

Les interactions protéines-glucides multivalentes initient les premiers contacts entre le virus/les bactéries et les cellules cibles, ce qui conduit finalement à une infection. La compréhension des structures et des modes de liaison impliqués est essentielle à la conception d'inhibiteurs multivalents spécifiques et puissants. Cependant, le manque d'informations structurelles sur ces protéines membranaires de surface cellulaires flexibles, complexes et multimères a souvent entravé ces efforts. Ici, nous rapportons que les points quantiques (QD) affichés avec un tableau dense de mono-/disaccharides sont des sondes puissantes pour les interactions protéine-glycane multivalentes. En utilisant une paire de lectines tétramériques étroitement apparentées, DC-SIGN et DC-SIGNR, qui se lient aux glycoprotéines du VIH et du virus Ebola (EBOV-GP) pour augmenter l'entrée virale et infecter les cellules cibles, nous montrons que ces QD dissèquent efficacement les différents modes de liaison DC-SIGN/R-glycane (tétra-/di-/monovalent) grâce à une combinaison de lectures multimodales : transfert d'énergie par résonance de Förster (FRET), mesure de la taille hydrodynamique et imagerie par microscopie électronique à transmission. Nous rapportons également une nouvelle méthode QD-FRET pour quantifier l'affinité de liaison QD-DC-SIGN/R, révélant que DC-SIGN se lie au QD >100 fois plus serré que DC-SIGNR. Ce résultat est cohérent avec l'efficacité de trans-infection plus élevée de DC-SIGN de certaines souches de VIH par rapport à DC-SIGNR. Enfin, nous montrons que les QD inhibent puissamment l'amélioration médiée par DC-SIGN de la transduction induite par EBOV-GP des cellules cibles avec des valeurs d'IC50 jusqu'à 0,7 nM, correspondant bien à leur constante de liaison DC-SIGN (Kd apparent = 0,6 nM) mesurée par FRET. Ces résultats suggèrent que les QD de glycanes sont de puissantes sondes multifonctionnelles pour disséquer la reconnaissance des ligands protéiques multivalents et prédire l'inhibition des glyconanoparticules de l'infection virale au niveau cellulaire. Las interacciones proteína-carbohidrato multivalentes inician los primeros contactos entre el virus/bacteria y las células diana, que en última instancia conducen a la infección. Comprender las estructuras y los modos de unión involucrados es vital para el diseño de inhibidores multivalentes específicos y potentes. Sin embargo, la falta de información estructural sobre dichas proteínas de membrana de superficie celular flexibles, complejas y multiméricas a menudo ha obstaculizado dichos esfuerzos. En el presente documento, informamos que los puntos cuánticos (QD) mostrados con una matriz densa de mono/disacáridos son potentes sondas para interacciones proteína-glicano multivalentes. Usando un par de lectinas tetraméricas estrechamente relacionadas, DC-SIGN y DC-SIGNR, que se unen a las glicoproteínas del VIH y del virus del Ébola (EBOV-GP) para aumentar la entrada viral e infectar las células diana, mostramos que tales QD diseccionan eficientemente los diferentes modos de unión DC-SIGN/R-glicano (tetra-/di-/monovalente) a través de una combinación de lecturas multimodales: transferencia de energía de resonancia de Förster (FRET), medición del tamaño hidrodinámico y obtención de imágenes POR microscopía electrónica de transmisión. También informamos de un nuevo método QD-FRET para cuantificar la afinidad de unión QD-DC-SIGN/R, que revela que DC-SIGN se une al QD >100 veces más fuerte que DC-SIGNR. Este resultado es consistente con la mayor eficiencia de transinfección de DC-SIGN de algunas cepas de VIH sobre DC-SIGNR. Finalmente, mostramos que los QD inhiben potentemente la mejora mediada por DC-SIGN de la transducción dirigida por EBOV-GP de células diana con valores de IC50 de hasta 0.7 nM, que coinciden bien con su constante de unión a DC-SIGN (Kd aparente = 0.6 nM) medida POR FRET. Estos resultados sugieren que los glucano-QD son potentes sondas multifuncionales para diseccionar el reconocimiento de proteínas-ligandos multivalentes y predecir la inhibición de gluconanopartículas de la infección viral a nivel celular. Multivalent protein–carbohydrate interactions initiate the first contacts between virus/bacteria and target cells, which ultimately lead to infection. Understanding the structures and binding modes involved is vital to the design of specific, potent multivalent inhibitors. However, the lack of structural information on such flexible, complex, and multimeric cell surface membrane proteins has often hampered such endeavors. Herein, we report that quantum dots (QDs) displayed with a dense array of mono-/disaccharides are powerful probes for multivalent protein–glycan interactions. Using a pair of closely related tetrameric lectins, DC-SIGN and DC-SIGNR, which bind to the HIV and Ebola virus glycoproteins (EBOV-GP) to augment viral entry and infect target cells, we show that such QDs efficiently dissect the different DC-SIGN/R-glycan binding modes (tetra-/di-/monovalent) through a combination of multimodal readouts: Förster resonance energy transfer (FRET), hydrodynamic size measurement, and transmission electron microscopy imaging. We also report a new QD-FRET method for quantifying QD-DC-SIGN/R binding affinity, revealing that DC-SIGN binds to the QD >100-fold tighter than does DC-SIGNR. This result is consistent with DC-SIGN's higher trans-infection efficiency of some HIV strains over DC-SIGNR. Finally, we show that the QDs potently inhibit DC-SIGN-mediated enhancement of EBOV-GP-driven transduction of target cells with IC50 values down to 0.7 nM, matching well to their DC-SIGN binding constant (apparent Kd = 0.6 nM) measured by FRET. These results suggest that the glycan-QDs are powerful multifunctional probes for dissecting multivalent protein–ligand recognition and predicting glyconanoparticle inhibition of virus infection at the cellular level. تبدأ تفاعلات البروتين والكربوهيدرات متعددة التكافؤ أول اتصالات بين الفيروس/البكتيريا والخلايا المستهدفة، مما يؤدي في النهاية إلى العدوى. يعد فهم الهياكل وأنماط الربط المعنية أمرًا حيويًا لتصميم مثبطات متعددة التكافؤ محددة وقوية. ومع ذلك، فإن نقص المعلومات الهيكلية عن هذه البروتينات الغشائية السطحية المرنة والمعقدة والمتعددة الخلايا قد أعاق في كثير من الأحيان مثل هذه المساعي. هنا، نذكر أن النقاط الكمومية (QDs) المعروضة مع مجموعة كثيفة من السكريات الأحادية/الثنائية هي تحقيقات قوية لتفاعلات البروتين والغليكان متعددة التكافؤ. باستخدام زوج من المحاضرات الرباعية ذات الصلة الوثيقة، DC - SIGN و DC - SIGNR، والتي ترتبط بالبروتينات السكرية لفيروس نقص المناعة البشرية وفيروس الإيبولا (EBOV - GP) لزيادة الدخول الفيروسي وإصابة الخلايا المستهدفة، نظهر أن أجهزة QD هذه تقوم بتشريح أوضاع ربط DC - SIGN/R - glycan المختلفة بكفاءة (رباعي/ثنائي/أحادي التكافؤ) من خلال مزيج من القراءات متعددة الوسائط: نقل طاقة رنين فورستر (FRET)، وقياس الحجم الهيدروديناميكي، والتصوير المجهري الإلكتروني للإرسال. نبلغ أيضًا عن طريقة QD - FRET جديدة لقياس تقارب ربط QD - DC - SIGN/R، مما يكشف أن DC - SIGN يرتبط بـ QD >100 ضعف أكثر من DC - SIGNR. تتوافق هذه النتيجة مع كفاءة نقل العدوى الأعلى لـ DC - SIGN لبعض سلالات فيروس نقص المناعة البشرية عبر DC - SIGNR. أخيرًا، نظهر أن QDS تمنع بشكل فعال التعزيز بوساطة DC - SIGN للتوصيل القائم على EBOV - GP للخلايا المستهدفة مع انخفاض قيم IC50 إلى 0.7 نانومتر، مما يتطابق جيدًا مع ثابت ربط DC - SIGN (ظاهر Kd = 0.6 نانومتر) المقاس بواسطة FRET. تشير هذه النتائج إلى أن جليكان- كيو دي إس هي تحقيقات قوية متعددة الوظائف لتشريح التعرف على البروتين متعدد التكافؤ والتنبؤ بتثبيط جسيمات جليكونان لعدوى الفيروس على المستوى الخلوي.

Higher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p=0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald chi2=4.071, OR=1.043, 95% CI 1.001-1.086, p<0.05), which was confirmed by Receiver Operating Curves (AUC=0.68, 95% CI=0.57-0.79, p=0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal.

Various mechanisms are involved in the process of ethanol-induced tissue impairment. Oxidative stress and its effects are among the most important. We compared the effects of antioxidant vitamins (vitamin C and E in combination) and steroids (testosterone and nandrolone separately) on the toxicity of ethanol in rats. Animals (male Wistar rats, n = 48) were randomised into following groups-Control, Ethanol, Testosterone, Ethanol + Testosterone, Ethanol + Nandrolone, Ethanol + Vitamins. Alcohol was given daily by gavage in a dose of 5 g/kg of body weight. On the 27th day of the study the animals were sacrificed by decapitation and tissue samples were taken. Metabolic status, parameters of the hepatic metabolism, hormone levels (testosterone, ACTH, corticosterone), lipoperoxidation markers (malondialdehyde and conjugated diens in forebrain cortex and in cerebellum) and advanced glycation end-products were analysed. Tissue samples underwent histological examination. Histological outcomes showed a protective effect of antioxidants on hepatic and cerebellar injury caused by chronic ethanol intake. Anabolic steroids protected especially the central nervous tissue against the toxicity of alcohol. Both, antioxidant vitamins and anabolic steroids protect against the ethanol-induced toxicity, however, this effect is tissue specific.