wDBTF: an integrated database resource for studying wheat transcription factor families

<p>Abstract</p> <p>Background</p> <p>Transcription factors (TFs) regulate gene expression by interacting with promoters of their target genes and are classified into families based on their DNA-binding domains. Genes coding for TFs have been identified in the sequences of model plant genomes. The rice (<it>Oryza sativa </it>spp. <it>japonica</it>) genome contains 2,384 TF gene models, which represent the mRNA transcript of a locus, classed into 63 families.</p> <p>Results</p> <p>We have created an extensive list of wheat (<it>Triticum aestivum </it>L) TF sequences based on sequence homology with rice TFs identified and classified in the Database of Rice Transcription Factors (DRTF). We have identified 7,112 wheat sequences (contigs and singletons) from a dataset of 1,033,960 expressed sequence tag and mRNA (ET) sequences available. This number is about three times the number of TFs in rice so proportionally is very similar if allowance is made for the hexaploidy of wheat. Of these sequences 3,820 encode gene products with a DNA-binding domain and thus were confirmed as potential regulators. These 3,820 sequences were classified into 40 families and 84 subfamilies and some members defined orphan families. The results were compiled in the Database of Wheat Transcription Factor (wDBTF), an inventory available on the web <url>http://wwwappli.nantes.inra.fr:8180/wDBFT/</url>. For each accession, a link to its library source and its Affymetrix identification number is provided. The positions of Pfam (protein family database) motifs were given when known.</p> <p>Conclusions</p> <p>wDBTF collates 3,820 wheat TF sequences validated by the presence of a DNA-binding domain out of 7,112 potential TF sequences identified from publicly available gene expression data. We also incorporated <it>in silico </it>expression data on these TFs into the database. Thus this database provides a major resource for systematic studies of TF families and their expression in wheat as illustrated here in a study of DOF family members expressed during seed development.</p

Dairy products and inflammation: a review of the clinical evidence

Inflammation is a major biological process regulating the interaction between organisms and the environment, including the diet. Because of the increase in chronic inflammatory diseases, and in light of the immune-regulatory properties of breastfeeding, the ability of dairy products to modulate inflammatory processes in humans is an important but unresolved issue. Here, we report a systematic review of 52 clinical trials investigating inflammatory markers in relation to the consumption of dairy products. An inflammatory score (IS) was defined to quantitatively evaluate this interaction. The IS was significantly positive for the entire data set, indicating an anti-inflammatory activity in humans. When the subjects were stratified according to their health status, the IS was strongly indicative of an anti-inflammatory activity in subjects with metabolic disorders and of a pro-inflammatory activity in subjects allergic to bovine milk. Stratifying the data by product categories associated both low-fat and high-fat products, as well as fermented products, with an anti-inflammatory activity. Remarkably, the literature is characterized by a large gap in knowledge on bioavailability of bioactive nutrients. Future research should thus better combine food and nutritional sciences to adequately follow the fate of these nutrients along the gastrointestinal and metabolic axes.info:eu-repo/semantics/publishedVersio

Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on metabolic and nutritional aspects. Effects of 3 g/day paracetamol for 14 days on fasting blood glutathione, plasma amino acids and sulfate, urinary paracetamol metabolites, and urinary metabolomic were studied in independently living older persons (five women, five men, mean (+/- SEM) age 74 +/- 1 years). Dietary intakes were recorded before and at the end of the treatment and ingested sulfur amino acids were evaluated. Fasting blood glutathione, plasma amino acids, and sulfate were unchanged. Urinary nitrogen excretion supported a preservation of whole body proteins, but large-scale urinary metabolomic analysis revealed an oxidation of some sulfur-containing compounds. Dietary protein intake was 13% higher at the end than before paracetamol treatment. Final sulfur amino acid intake reached 37 mg/kg/day. The increase in sulfur amino acid intake corresponded to half of the sulfur excreted in urinary paracetamol conjugates. In conclusion, older persons accommodated to long-term paracetamol treatment by increasing dietary protein intake without any mobilization of body proteins, but with decreased anti-oxidative defenses. The extra demand in sulfur amino acids led to a consumption far above the corresponding population-safe recommendation

RÔLE DE LA LEUCINE CONTRE LE DÉVELOPPEMENT DE LA SARCOPÉNIE

A progressive loss of muscle mass has been well described in both humans and rodents during ageing. This loss of proteins results from an imbalance between protein synthesis and degradation rates. Although some authors have shown a decrease of myofibrillar protein synthesis rates in human volunteers, this imbalance is not clearly apparent when basal rates of protein turnover are measured. A decrease in muscle protein synthesis stimulation has nevertheless been detected in ageing rats during the postprandial period, suggesting that the ‘meal signal’ is altered during ageing. Many results now suggest that aged muscle is less sensitive to the stimulatory effect of amino acids at physiological concentrations, but is still able to respond if the increase in aminoacidaemia is sufficiently large. Indeed, amino acids play an important role in regulating muscle protein turnover both in vitro and in vivo. Of amino acids, leucine seems to play the key role in regulating the metabolic function. It inhibits proteolysis and stimulates muscle protein synthesis independently of insulin. Leucine has been shown to act as a mediator, by modulating specifically the activities of intracellular kinases linked to the translation of proteins such as phosphatidylinositol 3_ kinase and mammalian target of rapamycin – 70 kDa ribosomal protein S6 (p70S6K) kinases. We recently demonstrated in vitro that protein synthesis in ageing rat muscles becomes resistant to the stimulatory effect of leucine in its physiological concentration range. Protein synthesis was however stimulated normally when the leucine concentration was increased well above its postprandial level. We also studied the effect of meal leucine supplementation on in vivo protein synthesis in adult and ageing rats. Leucine supplementation had no additional effect on muscle protein synthesis in adults but totally restored its stimulation in ageing rats. Whether chronic oral leucine supplementation would be beneficial for maintaining muscle protein mass in elderly humans remains to be studied.Une diminution de la masse musculaire au cours du vieillissement est aujourd'hui bien décrite chez l'Homme et l'animal. Cette perte de protéines résulte d'un déséquilibre entre synthèse et dégradation des protéines musculaires. Bien que certains auteurs aient pu montrer une diminution de la synthèse des protéines myofibrillaires chez l'Homme, ce déséquilibre est difficilement apparent dans la plupart des études menées à l'état post-absorptif. Cependant, une altération de la stimulation de la synthèse des protéines a été mise en évidence chez le rat âgé au cours de la phase post-prandiale suggérant que « l'effet repas » normalement observé était altéré au cours du vieillissement. Plusieurs travaux ont montré que le muscle âgé était moins sensible à l'effet anabolique des acides aminés aux concentrations physiologiques mais qu'il était toujours en mesure de répondre si d'importantes hyper-aminoacidémies étaient générées. En effet les acides aminés jouent un rôle majeur dans la régulation du métabolisme protéique, que ce soit in vivo ou in vitro. Parmi eux, la leucine semble être celui qui présente le plus fort effet. La leucine seule est capable d'inhiber la protéolyse et de stimuler la synthèse protéique indépendamment de l'insuline. Cet acide aminé, en plus d'être un substrat, est également un véritable médiateur cellulaire en modulant spécifiquement les activités de plusieurs kinases impliquées dans la régulation de l'initiation de la synthèse des protéines i.e phosphatidylinositol 3_ kinase and mammalian target of rapamycin-70 kDa ribosomal protein 56 (p70S6K) kinases. Nous avons montré récemment in vitro que la synthèse protéique musculaire devenait résistante à l'effet stimulateur de la leucine chez le rat âgé dans l'intervalle de ces concentrations physiologique. Cependant, si les concentrations de leucine étaient largement supérieures aux valeurs post-prandiales, la protéosynthèse était stimulée normalement. Nous avons donc étudié l'effet d'une supplémentation en leucine du régime sur la protéosynthèse du rat adulte et âgé in vivo. Cette supplémentation n'a pas eu d'effet additionnel chez l'adulte mais a permis de restaurer totalement la régulation post-prandiale du métabolisme protéique musculaire chez l'âgé. L'effet bénéfique d'une telle supplémentation en nutrition entérale chronique sur le maintien de la masse musculaire au cours du vieillissement reste cependant à étudier

A dietary supplementation with leucine and antioxidants is capable to accelerate muscle mass recovery after immobilization in adult rats

Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6-8 months) were subjected to unilateral hindlimb casting for 8 days (10-18) and then permitted to recover for 10 to 40 days (R10-R40). They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX) (10 to 18), AOX and leucine (AOX + LEU) (18 to R15) and LEU alone (R15 to R40). Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP) and post absorptive (PA) states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37%) in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40) due to a higher protein synthesis both in PA and PP states (+23% and 31% respectively, Experimental vs. Control diets, P<0.05, R40) without difference in trypsin-and chymotrypsin-like activities between diets. Thus, this nutritional supplementation accelerated the recovery of muscle mass via a stimulation of protein synthesis throughout the entire day (in the PP and PA states) and could be a promising strategy to be tested during recovery from bed rest in humans

En situation de catabolisme musculaire, les protéines de lactosérum permettent bien de restaurer un anabolisme musculaire post prandial mais d’une durée très transitoire probablement insuffisante pour limiter la fonte musculaire

En situation de catabolisme musculaire, les protéines de lactosérum permettent bien de restaurer un anabolisme musculaire post prandial mais d’une durée très transitoire probablement insuffisante pour limiter la fonte musculair

Whey proteins promote post prandial positive nitrogen balance in a muscle wasting situation but probably for a too short period of time to translate into muscle sparing

Background and aims: Muscle wasting occurred by an imbalance of muscle protein metabolism. Most of catabolic states are characterized by both an insulin and amino acid resistance which result into a food intake inefficiency to promote positive nitrogen balance during the post prandial period. So far, fast digested proteins (i.e whey) have been shown to be more efficient than casein to promote a stimulation of muscle protein synthesis (PS) in such situations; however, muscle mass is rarely improved. Our hypothesis is that this stimulation occurs only for a short period of time in the fed state, which remains insufficient to induce a significant increase in muscle mass. To address this point, a PS and proteolysis (PRO) kinetic study at the muscle level is required.Methods: Adult mini pigs were catheterized into both the femoral artery and vein and infused with 13C Phe to assess continuously) muscle PS and PRO in the hindlimb by the substrate and tracer arterio-venous difference method (every 30min before (PA) and after food intake). The catabolic state was induced by glucocorticoid treatment (8d); both casein and whey effects on PS and PRO were tested over time for 6.5 h.Results: After glucocorticoids, animals were in negative nitrogen balance at PA and casein intake had no effect on both PS and PRO and animals remained in negative nitrogen balance during the whole postprandial period. With whey, treated animals are able to generate a positive nitrogen balance for 120min after food intake (PS:+40% and PRO:-20%) which decreased thereafter along the postprandial period. Glucocorticoids were associated with insulin resistance (postprandial period: increased insulin/glycaemia). When fed whey, animals still presented hyperinsulinemia but normalized postprandial glycaemia.Conclusions. Whey are more efficient to generate positive muscle nitrogen balance in catabolic states but it remained only for a short period of time which may limit their efficiency on muscle wasting. Nutritional strategies have to be studied to optimize the duration of whey efficiency in the catabolic states. By contrast, whey are interesting to control post prandial hyperglycaemia in muscle protein wasting situations

4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia

Epub ahead of printBACKGROUND: Sarcopenia is the loss of muscle mass/function that occurs during the aging process. The links between mechanistic target of rapamycin (mTOR) activity and muscle development are largely documented, but the role of its downstream targets in the development of sarcopenia is poorly understood. Eukaryotic initiation factor 4E-binding proteins (4E-BPs) are targets of mTOR that repress mRNA translation initiation and are involved in the control of several physiological processes. However, their role in skeletal muscle is still poorly understood. The goal of this study was to assess how loss of 4E-BP1 and 4E-BP2 expression impacts skeletal muscle function and homeostasis in aged mice and to characterize the associated metabolic changes by metabolomic and lipidomic profiling. METHODS: Twenty-four-month-old wild-type and whole body 4E-BP1/4E-BP2 double knockout (DKO) mice were used to measure muscle mass and function. Protein homeostasis was measured ex vivo in extensor digitorum longus by incorporation of l-[U-(14) C]phenylalanine, and metabolomic and lipidomic profiling of skeletal muscle was performed by Metabolon, Inc. RESULTS: The 4E-BP1/2 DKO mice exhibited an increase in muscle mass that was associated with increased grip strength (P < 0.05). Protein synthesis was higher under both basal (+102%, P < 0.05) and stimulated conditions (+65%, P < 0.05) in DKO skeletal muscle. Metabolomic and complex lipid analysis of skeletal muscle revealed robust differences pertaining to amino acid homeostasis, carbohydrate abundance, and certain aspects of lipid metabolism. In particular, levels of most free amino acids were lower within the 4E-BP1/2 DKO muscle. Interestingly, although glucose levels were unchanged, differences were observed in the isobaric compound maltitol/lactitol (33-fold increase, P < 0.01) and in several additional carbohydrate compounds. 4E-BP1/2 depletion also resulted in accumulation of medium-chain acylcarnitines and a 20% lower C2/C0 acylcarnitine ratio (P < 0.01) indicative of reduced beta-oxidation. CONCLUSIONS: Taken together, these findings demonstrate that deletion of 4E-BPs is associated with perturbed energy metabolism in skeletal muscle and could have beneficial effects on skeletal muscle mass and function in aging mice. They also identify 4E-BPs as potential targets for the treatment of sarcopenia

Effects of leucine supplementation and resistance exercise on dexamethasone-induced muscle atrophy and insulin resistance in rats

Objective: We aimed to evaluate the effects of resistance exercise (RE) and leucine (LEU) supplementation on dexamethasone (DEXA)-induced muscle atrophy and insulin resistance.Methods: Male Wistar rats were randomly divided into DEXA(DEX), DEXA + RE (DEX-RE), DEXA + LEU (DEX-LEU), and DEXA + RE + LEU (DEX-RE-LEU) groups. Each group received DEXA 5 mg . kg(-1) . d(-1) for 7 d from drinking water and were pair-fed to the DEX group; LEU-supplemented groups received 0.135 g . kg(-1) . d(-1) through gavage for 7 d; the RE protocol was based on three sessions of squat-type exercise composed by three sets of 10 repetitions at 70% of maximal voluntary strength capacity.Results: the plantaris mass was significantly greater in both trained groups compared with the non-trained groups. Muscle cross-sectional area and fiber areas did not differ between groups. Both trained groups displayed significant increases in the number of intermediated fibers (IIa/IIx), a decreased number of fast-twitch fibers (IIb), an increased ratio of the proteins phospho(Ser2448)/ total mammalian target of rapamycin and phospho(Thr389)/total 70-kDa ribosomal protein S6 kinase. and a decreased ratio of phospho(Ser253)/total Forkhead box protein-3a. Plasma glucose was significantly increased in the DEX-LEU group compared with the DEX group and RE significantly decreased hyperglycemia. the DEX-LEU group displayed decreased glucose transporter-4 translocation compared with the DEX group and RE restored this response. LEU supplementation worsened insulin sensitivity and did not attenuate muscle wasting in rats treated with DEXA. Conversely, RE modulated glucose homeostasis and fiber type transition in the plantaris muscle.Conclusion: Resistance exercise but not LEU supplementation promoted fiber type transition and improved glucose homeostasis in DEXA-treated rats. (C) 2012 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Lab Appl Nutr & Metab, Sch Phys Educ & Sports, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, São Paulo, BrazilUniv São Paulo, Lab Mol & Cellular Physiol Exercise, Sch Phys Educ & Sports, São Paulo, BrazilUniv São Paulo, Sch Med, Lab Expt Hypertens, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilClermont Univ, UFR Med, UMR Nutr Humaine 1019, Clermont Ferrand, FranceINRA, UMR Unite Nutr Humaine 1019, F-63122 St Genes Champanelle, FranceUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilFAPESP: 08/51090-1FAPESP: 10/07062-3FAPESP: 10/10852-6FAPESP: 11/04690-6Web of Scienc

Efficacy of non-pharmacological interventions to treat malnutrition in older persons : A systematic review and meta-analysis. The SENATOR project ONTOP series and MaNuEL Knowledge Hub project

The preparation of this paper was supported by the MalNutrition in the ELderly (MaNuEL) knowledge hub. MaNuEL is supported by the Joint Programming Initiative ‘Healthy Diet for a Healthy Life’. The MaNuEL funding agencies supporting this paper are (in alphabetical order of participating Member State): France: Ecole Supérieure d’Agricultires (ESA); Germany: Federal Ministry of Food and Agriculture (BMEL) represented by Federal Office for Agriculture and Food (BLE); The Netherlands: The Netherlands Organisation for Health Research and Development (ZonMw). This work was also supported by the SENATOR trial (FP7-HEALTH-2012-305930).Peer reviewedPostprin