A new protein curbs the hypertrophic effect of myostatin inhibition, adding remarkable endurance to motor performance in mice

Current efforts to improve muscle performance are focused on muscle trophism via inhibition of the myostatin pathway: however they have been unsuccessful in the clinic to date. In this study, a novel protein has been created by combining the soluble activin receptor, a strong myostatin inhibitor, to the C-terminal agrin nLG3 domain (ActR-Fc-nLG3) involved in the development and maintenance of neuromuscular junctions. Both domains are connected via the constant region of an Igg1 monoclonal antibody. Surprisingly, young male mice treated with ActR-Fc-nLG3 showed a remarkably increased endurance in the rotarod test, significantly longer than the single domain compounds ActR-Fc and Fc-nLG3 treated animals. This increase in endurance was accompanied by only a moderate increase in body weights and wet muscle weights of ActR-Fc-nLG3 treated animals and were lower than expected. The myostatin inhibitor ActR-Fc induced, as expected, a highly significant increase in body and muscle weights compared to control animals and ActR-Fc-nLG3 treated animals. Moreover, the prolonged endurance effect was not observed when ActR-Fc and Fc-nLG3 were dosed simultaneously as a mixture and the body and muscle weights of these animals were very similar to ActR-Fc treated animals, indicating that both domains need to be on one molecule. Muscle morphology induced by ActR-Fc-nLG3 did not appear to be changed however, close examination of the neuromuscular junction showed significantly increased acetylcholine receptor surface area for ActR-Fc-nLG3 treated animals compared to controls. This result is consistent with published observations that endurance training in rats increased acetylcholine receptor quantity at neuromuscular junctions and provide evidence that improving nerve-muscle interaction could be an important factor for sustaining long term muscle activity

Impact on Tannat wines aroma produced by different yeast using three vinification systems

Vinifications were conducted using pure cultures of Saccharomyces cerevisiae, and mixed cultures by sequential inoculation of a Hanseniaspora vineae (T02/05F) and Hanseniaspora clermontiae (A10/82F), with a Saccharomyces cerevisiae conventional strain. The vinification systems applied to Tannat grapes were defined: semipilot, pilot and industrial scale. Fifty-one volatile compounds were identified in all the vinifications, sixteen of them were above the aroma threshold values and potentially contributed to the final sensory profiles. A sensory characterization of aroma was carried out using the projective mapping technique, with forty-eight consumers who made evaluation of the three vinifications. Multiple factorial analysis was used to compare the chemical and sensory data to find correlations. The results obtained from both methodologies were coincident, confirming the aromatic tendencies found in the different vinifications. Both studies demonstrated that wines obtained by semipilot scale was characterized by descriptors associated with “chemical” and “floral”; those from pilot vinification by the “spicy” descriptor; while industrial vinification produced wines described as “fruit” and “wood”

Updating Prospective Self-Efficacy Beliefs About Cardiac Interoception in Anorexia Nervosa: An Experimental and Computational Study.

Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy per se, they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness

Chemical characterization and enological potential of less frequent red grape Uruguayan varieties by study secondary metabolites

Study of secondary grape metabolites, such as polyphenol compounds (anthocyanins, flavonols, flavan-3-ols), volatile compounds present in grapes in both free and glycoside forms (monoterpenols, norisoprenoids, benzenoids), allowed us to characterize grape varieties and to suggest the best winemaking practices to maximize their enological potential. The Vitis viníferas studied in the present work are less frequent red grape varieties cultivated in small vineyards in southern Uruguay (Montevideo and Canelones Provinces): Ancellota, Aspiran Bouschet (syn. Lacryma Christi), Marselan (Grenache × Cabernet Sauvignon), Arinarnoa (Tannat × Cabernet Sauvignon), Egiodola (Abouriou × Tinta Negra Mole) and Caladoc (Malbec × Grenache)

Estrategias combinadas para la obtención de un vino Tannat con un contenido moderado de alcohol

Resumen En este trabajo se buscó a través de la combinación de 2 estrategias reducir el contenido de alcohol en vinos de la variedad Tannat. La primera estrategia consistió en el screening dentro de clones uruguayos de Tannat Con este fin se muestrearon durante tres vendimias consecutivas 10 clones uruguayos de Tannat y se utilizó como referencia el clon francés 717 en viñedos. De los clones estudiados 4 presentaron durante la vendimia 2023 un contenido significativamente inferior de alcohol que el clon 717, manteniendo los componentes responsables de su calidad sensorial (aromas glicosidados, antocianos totales). Mientras que la segunda estrategia fue realizar un screening de levaduras no-Saccharomyces nativas aisladas de viñedos uruguayos para utilizar en conjunto con la cepa Saccharomyces cerevisiae Lalvin BM4x4 Lalleman (utilizada como referencia para vinificar vino Tannat). Se estudió el comportamiento de 4 géneros de levaduras (Candida zemplinina, Metschnikowia pulcherrima, Metschnikowia fructicola y Hanseniaspora uvarum), en microvinificaciones en símil vino. Estas estrategias fueron seleccionada por que además de permitir la reducción de alcohol en vinos Tannat en forma conjunta le aportan una identidad propia de nuestro país

Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain

De-Novo Assembly and Analysis of the Heterozygous Triploid Genome of the Wine Spoilage Yeast Dekkera bruxellensis AWRI1499

Despite its industrial importance, the yeast species Dekkera (Brettanomyces) bruxellensis has remained poorly understood at the genetic level. In this study we describe whole genome sequencing and analysis for a prevalent wine spoilage strain, AWRI1499. The 12.7 Mb assembly, consisting of 324 contigs in 99 scaffolds (super-contigs) at 26-fold coverage, exhibits a relatively high density of single nucleotide polymorphisms (SNPs). Haplotype sampling for 1.2% of open reading frames suggested that the D. bruxellensis AWRI1499 genome is comprised of a moderately heterozygous diploid genome, in combination with a divergent haploid genome. Gene content analysis revealed enrichment in membrane proteins, particularly transporters, along with oxidoreductase enzymes. Availability of this assembly and annotation provides a resource for further investigation of genomic organization in this species, and functional characterization of genes that may confer important phenotypic traits

Epilepsy Caused by an Abnormal Alternative Splicing with Dosage Effect of the SV2A Gene in a Chicken Model

Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology