The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase ...(OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation.
Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for ...interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF.
•After appropriate acclimation, sustainable biogas production is achievable from low C/N substrates.•Metagenomic analysis reveals alterations in the microbial community.•High biogas yields in ...anaerobic degradation (AD) of protein-rich monosubstrates.•Addition of selected protein-degrading strains leads to effective AD.•Selected strains lead to sustainable AD without acclimation.
This study demonstrates that appropriate adaptation of the microbial community to protein-rich biomass can lead to sustainable biogas production. The process of acclimation to these unusual mono-substrates was controlled by the protease activity of the microbial community. Meat extract (C/N=3.32) and kitchen waste (C/N=12.43) were used as biogas substrates. Metagenome analysis highlighted several mesophilic strains that displayed a preference for protein degradation. Bacillus coagulans, Bacillus subtilis and Pseudomonas fluorescens were chosen for detailed investigation. Pure cultures were added to biogas reactors fed solely with protein-rich substrates. The bioaugmentation resulted in a 50% increase in CH4 production even without any acclimation. The survival and biological activity of the added bacteria were followed in fed-batch fermenters by qPCR. Stable biogas production was observed for an extended period of time in laboratory CSTR reactors fed with biomass of low C/N.
Introduction
Rumination is a transdiagnostic risk factor to psychopathology that has mostly been studied in relation to depression (Nolen-Hoeksema, 1991). However, rumination may also occur in ...response to positive events and emotions (Feldman et al., 2008), and may be a protective factor as it is associated with higher positive affect (Harding et al., 2017).
Objectives
We aimed to examine ruminative response to positive affect (RPA) in daily life and explore its relationship with daily positive and negative affect. We hypothesized that daily positive and negative affect would be associated with daily RPA even after controlling for trait-level RPA and depressive rumination.
Methods
We carried out a daily diary study with university students (n=178). After filling out the baseline survey assessing trait-level rumination, participants had to answer short surveys online about their daily affect and daily rumination every evening for 10 consecutive days. We analyzed our data with multilevel regression in R.
Results
In line with our expectations, daily RPA was significantly associated with daily positive (β=0.16) and negative affect (β=-0.07), while trait-level rumination scores were not significantly associated with daily positive and negative affect. The within-person relationship was stronger between RPA and positive affect (β=0.17) than the between-person relationship (β=0.09). Daily and trait-level rumination were weakly correlated (r=0.218-0.284).
Conclusions
Under ecologically valid conditions, we found that daily rumination was more important in daily affective experiences than trait-level rumination. Understanding whether one’s current affect is more strongly associated with trait-level, state-level or even contextual factors may yield better intervention strategies for affective disorders.
Disclosure
No significant relationships.
In this study, upper critical values of the temperature-humidity index (THI) were determined in Holstein bull calves (n = 16) based on noninvasive physiological variables. Meteorological and ...animal-based data were recorded for a 4-d period following a 24-h habituation. The estimated upper critical THI values based on the assessment of respiratory rate, rectal temperature, ear temperature, heart rate, and salivary cortisol concentrations were 82.4, 88.1, 83.0, 78.3, and 88.8, respectively. We inferred that welfare of young calves may be compromised above a THI of 78 and that calves experience significant heat stress above a THI of 88. Based on the present findings, upper critical THI should be considered to minimize the duration of impaired welfare during summer heat stress episodes.
Metagenomics is a helpful tool for the analysis of unculturable organisms and viruses. Viruses that target bacteria and archaea play important roles in the microbial diversity of various ecosystems. ...Here we show that Methanosarcina virus MV (MetMV), the second Methanosarcina sp. virus with a completely determined genome, is characteristic of hydrocarbon pollution in environmental (soil and water) samples. It was highly abundant in Hungarian hydrocarbon polluted samples and its genome was also present in the NCBI SRA database containing reads from hydrocarbon polluted samples collected in Canada, indicating the stability of its niche and the marker feature of this virus. MetMV, as the only currently identified marker virus for pollution in environmental samples, could contribute to the understanding of the complicated network of prokaryotes and their viruses driving the decomposition of environmental pollutants.
Yeast Atg8 and its homologs are involved in autophagosome biogenesis in all eukaryotes. These are the most widely used markers for autophagy thanks to the association of their lipidated forms with ...autophagic membranes. The Atg8 protein family expanded in animals and plants, with most
species having two Atg8 homologs. In this Brief Report, we use clear-cut genetic analysis in
to show that lipidated Atg8a is required for autophagy, while its non-lipidated form is essential for developmentally programmed larval midgut elimination and viability. In contrast, expression of Atg8b is restricted to the male germline and its loss causes male sterility without affecting autophagy. We find that high expression of non-lipidated Atg8b in the male germline is required for fertility. Consistent with these non-canonical functions of Atg8 proteins, loss of
genes required for Atg8 lipidation lead to autophagy defects but do not cause lethality or male sterility.
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