Concerted changes in N and C primary metabolism in alfalfa (Medicago sativa) under water restriction

Although the mechanisms of nodule N2 fixation in legumes are now well documented, some uncertainty remains on the metabolic consequences of water deficit. In most cases, little consideration is given to other organs and, therefore, the coordinated changes in metabolism in leaves, roots, and nodules are not well known. Here, the effect of water restriction on exclusively N2-fixing alfalfa (Medicago sativa L.) plants was investigated, and proteomic, metabolomic, and physiological analyses were carried out. It is shown that the inhibition of nitrogenase activity caused by water restriction was accompanied by concerted alterations in metabolic pathways in nodules, leaves, and roots. The data suggest that nodule metabolism and metabolic exchange between plant organs nearly reached homeostasis in asparagine synthesis and partitioning, as well as the N demand from leaves. Typically, there was (i) a stimulation of the anaplerotic pathway to sustain the provision of C skeletons for amino acid (e.g. glutamate and proline) synthesis; (ii) re-allocation of glycolytic products to alanine and serine/glycine; and (iii) subtle changes in redox metabolites suggesting the implication of a slight oxidative stress. Furthermore, water restriction caused little change in both photosynthetic efficiency and respiratory cost of N2 fixation by nodules. In other words, the results suggest that under water stress, nodule metabolism follows a compromise between physiological imperatives (N demand, oxidative stress) and the lower input to sustain catabolism.

Green tea catechin inhibits fatty acid synthase without stimulating carnitine Palmitoyltransferase-1 or inducing weight loss in experimental animals

Background: The enzyme fatty acid synthase (FASN) is highly expressed in many human carcinomas and its inhibition is cytotoxic to human cancer cells. The use of FASN inhibitors has been limited until now by anorexia and weight loss, which is associated with the stimulation of fatty acid oxidation. Materials and Methods: The in vitro effect of (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism enzymes, on apoptosis and on cell signalling was evaluated. In vivo, the effect of EGCG on animal body weight was addressed. Results: EGCG inhibited FASN activity, induced apoptosis and caused a marked decrease of human epidermal growth factor receptor 2 (HER2), phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular (signal)-regulated kinase (ERK) 1/2 proteins, in breast cancer cells. EGCG did not induce a stimulatory effect on CPT-1 activity in vitro (84% of control), or on animal body weight in vivo (99% of control). Conclusion: EGCG is a FASN inhibitor with anticancer activity which does not exhibit cross-activation of fatty acid oxidation and does not induce weight loss, suggesting its potential use as an anticancer drug.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response

Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements.

Flujo de energía en el ecosistema fluvial : análisis del metabolismo

Capítol 20 del llibre 'Conceptos y técnicas en ecología fluvial' que es refereix al metabolisme fluvial

GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish

Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.

Foliar photochemical processes and carbon metabolism under favourable and adverse winter conditions in a Mediterranean mixed forest, Catalonia (Spain)

Evergreen trees in the Mediterranean region must cope with a wide range of environmental stresses from summer drought to winter cold. The mildness of Mediterranean winters can periodically lead to favourable environmental conditions above the threshold for a positive carbon balance, benefitting evergreen woody species more than deciduous ones. The comparatively lower solar energy input in winter decreases the foliar light saturation point. This leads to a higher susceptibility to photoinhibitory stress especially when chilly (< 12 C) or freezing temperatures (< 0 C) coincide with clear skies and relatively high solar irradiances. Nonetheless, the advantage of evergreen species that are able to photosynthesize all year round where a significant fraction can be attributed to winter months, compensates for the lower carbon uptake during spring and summer in comparison to deciduous species. We investigated the ecophysiological behaviour of three co-occurring mature evergreen tree species (Quercus ilex L., Pinus halepensis Mill., and Arbutus unedo L.). Therefore, we collected twigs from the field during a period of mild winter conditions and after a sudden cold period. After both periods, the state of the photosynthetic machinery was tested in the laboratory by estimating the foliar photosynthetic potential with CO2 response curves in parallel with chlorophyll fluorescence measurements. The studied evergreen tree species benefited strongly from mild winter conditions by exhibiting extraordinarily high photosynthetic potentials. A sudden period of frost, however, negatively affected the photosynthetic apparatus, leading to significant decreases in key physiological parameters such as the maximum carboxylation velocity (Vc,max), the maximum photosynthetic electron transport rate (Jmax), and the optimal fluorometric quantum yield of photosystem II (Fv/Fm). The responses of Vc,max and Jmax were highly species specific, with Q. ilex exhibiting the highest and P. halepensis the lowest reductions. In contrast, the optimal fluorometric quantum yield of photosystem II (Fv/Fm) was significantly lower in A. unedo after the cold period. The leaf position played an important role in Q. ilex showing a stronger winter effect on sunlit leaves in comparison to shaded leaves. Our results generally agreed with the previous classifications of photoinhibition-tolerant (P. halepensis) and photoinhibitionavoiding (Q. ilex) species on the basis of their susceptibility to dynamic photoinhibition, whereas A. unedo was the least tolerant to photoinhibition, which was chronic in this species. Q. ilex and P. halepensis seem to follow contrasting photoprotective strategies. However, they seemed equally successful under the prevailing conditions exhibiting an adaptive advantage over A. unedo. These results show that our understanding of the dynamics of interspecific competition in Mediterranean ecosystems requires consideration of the physiological behaviour during winter which may have important implications for long-term carbon budgets and growth trends.

Mitochondrial fatty acid oxidation in obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.

Disseny i elaboració d'un gimnàs on-line

L’evolució que ha experimentat la societat, les grans ciutats, la industrialització i molts altres factors han modificat l’estil de vida de les persones accentuant-ne, irremediablement, el sedentarisme i l’abstinència de realitzar exercici físic. La pràctica esportiva i/o d’exercici físic realitzada sota les condicions recomanades pels professionals, és beneficiosa per millorar el nivell de salut o mantenir-lo en tot el possible, ja que provoca modificacions beneficioses sobre el metabolisme, el sistema cardiovascular i l’aparell locomotor. Lamentablement, l’hàbit de realitzar exercici físic no és comú en totes les persones, ja sigui per l’estil de vida que genera incompatibilitats d’horaris amb la feina, fills i familiars o bé per mandra o desgana d’haver d’aprofitar aquelles estones de temps lliure per dedicar-los al culte del cos i de la salut. Els efectes negatius que suposa una modalitat de vida sedentària per a la salut són notablement elevats, amb la qual cosa, cal buscar sistemes per augmentar l’ interès de la població per la pràctica de l’esport i l’activitat física. La creació d’aquest projecte neix de la idea d’unir el fet d’enginyar un mètode per incrementar l’interès de les persones per l’exercici físic amb els avenços tecnològics que s’han realitzat aquesta última dècada relacionats amb el desenvolupament web i multimèdia. A grans trets, la idea general d’aquest projecte es basa en el cas d’un gimnàs real i en actiu, amb necessitat de crear un portal web que serveixi alhora de pàgina web informativa i d’eina de gestió acadèmica del centre proporcionant certes funcionalitats als clients tot presentant-los una nova modalitat de realitzar exercici físic dirigit: realitzar-lo des de casa. Per desenvolupar tot el sistema informàtic que ho durà a terme, després de realitzar una recerca, anàlisi i elecció de les eines mitjançant les quals poder-ho realitzar, s’ha optat per crear l’entorn web mitjançant els llenguatges HTML i PHP en combinació amb els fulls d’estil CSS. Pel que fa a l’entorn de desenvolupament, s’ha utilitzat Notepad++ i com a entorn de proves, WAMP Server. Per últim, pel que fa a la transmissió del contingut multimèdia (vídeos de les sessions d’activitats) s’ha utilitzat Flash Media Interactive Server en combinació de Flash Media Live Encoder per codificar-ne el contingut. L’usuari final, des de qualsevol punt del planeta, podrà realitzar (sempre i quan disposi del temps i el material necessari i una connexió a Internet) en temps real i en directe les classes dirigides que es realitzen al centre. Tanmateix, també s’ha desenvolupat una botiga virtual on qualsevol persona podrà comprar-hi, entre d’altres coses relacionades amb la pràctica de l’exercici físic, tot el material necessari per realitzar qualsevol de les activitats que s’imparteixen al gimnàs i ho rebrà còmodament a casa. Aprofitar unes circumstàncies econòmiques adverses per generar una nova manera de captar clients proporcionant-los una alternativa econòmica, diferent, nova i original d’anar al gimnàs. Temps de crisis, temps d’oportunitats. Aquesta és la moralitat que pretén donar aquest projecte.