A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis

The ribosomal protein S6 kinase 1 (S6K1) is a relevant effector downstream of the mammalian target of rapamycin complex 1 (mTORC1), best known for its role in the control of lipid homeostasis. Consistent with this, mice lacking the S6k1 gene have a defect in their ability to induce the commitment of fat precursor cells to the adipogenic lineage, which contributes to a significant reduction of fat mass. Here, we assess the therapeutic blockage of S6K1 in diet-induced obese mice challenged with LY2584702 tosylate, a specific oral S6K1 inhibitor initially developed for the treatment of solid tumors. We show that diminished S6K1 activity hampers fat mass expansion and ameliorates dyslipidemia and hepatic steatosis, while modifying transcriptome-wide gene expression programs relevant for adipose and liver function. Accordingly, decreased mTORC1 signaling in fat (but increased in the liver) segregated with defective epithelial-mesenchymal transition and the impaired expression of Cd36 (coding for a fatty acid translocase) and Lgals1 (Galectin 1) in both tissues. All these factors combined align with reduced adipocyte size and improved lipidomic signatures in the liver, while hepatic steatosis and hypertriglyceridemia were improved in treatments lasting either 3 months or 6 weeks

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Establishment of proliferating callus from roots, cotyledons and Hypocotyls of carob (ceratoniia siliqua L.) seedlings

Roots, cotyledons and hypocotyls of Ceratonia siliqua, excised from sterile seedlings produced ed callus on agar with a defined nutrient medium. Callus production takes place in 2-month old ciltures. Percentage callus formation in cotyledons and hypocotyls was greater than in roots. In the cotyledons, callus induction was stimulated in the veins with differentiation of both shoots and roots. Callus growth in the second explant was greatly increased when coconut milk was added to the medium where organogenesis eventually occurred

Ethylene production by carob (Ceratonia siliqua) callus cultures on varying media

Carob callus from hypotocotyl segments produced ethylene in different amounts which were related to the composition of the medium and age of the callus. Both light and darkness stimulated high levels of ethylene production. No correlation was found between growth rate and ethylene production under dark conditions. In the light, a significant correlation was found, indicating that etylene production and growth rate follow one another. Culture medium was the most important factor in controlling the growth rate and ethylene production. The highest values of ethylene production were obtained on media showing highest callus growth rate. These studies seem to indicate that most of the ethylene produced is a by-product of metabolic changes during carob callus development, though, under certain conditions, the initial evolution could regulate growth

La fijacion biologica de nitrogeno atmosferico y la produccion vegetal

Biological Nitrogen Fixation shows itself as a promising means to lower costs in plant protein production. It offers the scientist with a wide spectrum of possibilities to develop, by further research, what is already known on that process. Meanwhile, nitrogen fixation must be put to work and to that end a range of biological systems existing in Nature are outlined, though briefly, in the present article, mainly covering symbiotic, as well as free-living nitrogen-fixers. The use of synthetic nitrogen fertilizer is at stake due to increased fossil fuel prices, and trying to bring up new, not so costly alternatives, appears to be the point at issue. Suggestions on the use of the various systems, supported by experimental data, are given, and the attention of the reader called upon those points which should merit further research. La Fijación Biológica de Nitrógeno se muestra como un medio de reducir costes en la producción de proteína vegetal. El científico dispone de un amplio campo donde desarrolar unas investigaciones que se encuentran en constante dinâmica. Mientras tanto, la fijación de nitrógeno ha de utilizarse en la práctica al nivel que los conocimientos actuales nos lo permitan. Con este propósito se incluyen una serie de sistemas naturales capaces de ejercer aquella función, principalmente simbióticos y libres, respectivamente. El uso de fertilizantes nitrogenados de síntesis industrial se presenta cada día más problemático debido a los precios de los combustibles fósiles. Por ello han de desarrollarse nuevas alternativas, no tan costosas, sustitutivas, o en su caso complementarias. Se mencionan las posibilidades que los distintos sistemas nos ofrecen, apoyadas en resultados experimentales, así como aquellos aspectos del processo que merecen la atención del investigador

Burkholderia ferrariae sp. nov., a novel bacterium isolated from an iron ore in Brazil.

A Gram-negative, non-spore-forming bacterial strain with the ability to solubilize highly insoluble phosphatic minerals was isolated from a high-phosphorous iron ore from Minas Gerais State, Brazil. This strain, designated FeGl01(T), was subjected to a polyphasic; taxonomic investigation. Comparative 16S rRNA gene sequence analysis indicated that it formed a distinct phylogenetic lineage within the genus Burkholderia together with several other species of the genus, e.g. Burkholderia sacchari, Burkholderia tropica and Burkholderia unamae. Partial nucleotide sequencing and analysis of the recA gene roughly corroborated the phylogenetic position of strain FeGl01(T) within the genus Burkholderia. The chemotaxonomic properties of strain FeGl01(T), such as ubiquinone Q-8 as the predominant quinone system and C-16:0, C-17:0 cyclo, C-18:1 omega 7c and C-19:0 omega 8c cyclo as the major fatty acids, were also consistent with its classification within the genus Burkholderia. DNA-DNA hybridization experiments between strain FeGl01(T) and the type strains of B. unamae, B. sacchari and B. tropica yielded reassociation values of 40% or lower, which, together with qualitative and quantitative differences in fatty acid composition and with differences in several phenotypic traits, support the separation of the new isolate from the phylogenetically most closely related species. Therefore, it is suggested that strain FeGl01(T) represents a novel species of the genus Burkholderia, for which the name Burkholderia ferrariae sp. nov. is proposed. The type strain is FeGl01(T) (= LMG 23612(T) = CECT 7171(T) = DSM 18251(T)).We wish to thank Dr Jesu´ s Caballero-Mellado (UNAM, Cuernavaca, Mexico) for kindly providing the type strains of B. unamae and B. tropica. A. V. is indebted to the Ministry of Education and Science of Spain for a post-doctoral fellowship at The Hebrew University of Jerusalem. P. D. acknowledges financial support, in the form of a doctoral scholarship, of the Venezuelan Foundation for Science, Technology and Innovation (FONACIT) and the Simo´n Bolı´var University of Venezuela.Peer reviewe

Plant species diversity, plant biomass and responses of the soil community on abandoned land across Europe: idiosyncracy or above-belowground time lags

We examined the relationship between plant species diversity, productivity and the development of the soil community during early secondary succession on former arable land across Europe. We tested the hypothesis that increasing the initial plant species diversity enhances the biomass production and consequently stimulates soil microbial biomass and abundance of soil invertebrates. We performed five identical field experiments on abandoned arable land in five European countries (CZ, NL, SE, SP and UK) which allowed us to test our hypothesis in a range of climate, soil and other environmental factors that varied between the experimental sites. The initial plant diversity was altered by sowing seed mixtures of mid-successional grassland species with two or five grass species, one or five legumes and one or five forbs. The results of low and high sown diversity treatments were compared with plots that were naturally colonized by species present in the seed bank. In three out of the five field sites, there was no correlation between plant species number and plant biomass production, one site had a positive and the other a negative relation. Treatments with a high diversity seed mixture had a higher biomass than the naturally colonized plots. However, there was no significant difference between high and low sown diversity plots at four out of five sites. The three-year study did not give any evidence of a general bottom-up effect from increased plant biomass on biomass of bacteria, saprophytic fungi or abundance of microarthropods. The biomass of arbuscular mycorrhizal was negatively related to plant biomass. The abundance of nematodes increased after abandonment and was related to plant biomass at four sites. Our results support the hypothesis that plant species diversity may have idiosyncratic effects on soil communities, even though studies on a longer term could reveal time lags in the response to changes in composition and biomass production of plant communitie