Catabolic Activity Research Articles

Biochemical indicators of sports achievements in highly qualified wrestlers

Objective: to conduct comparative analysis of blood biochemical parameters (urea, ALT, AST, creatinkinase, cortisol, testosterone and testosterone / cortisol ratio) in groups of high­class wrestlers with different levels of sports achievements.Materials and methods: male athletes (n = 78), members of the Russian national team in one of the types of wrestling (the average age is 25.2 (21.5–28.9) years, the average weight is 76.9 (68.4–83.4) kg) were recruited to this study. The examined athletes were divided into two groups according to their sporting achievements. The first one — SHA group (super­high achievements) which included athletes (n = 19) who had victories and prizes at the largest international competitions (European, World, Olympic Games), and the second group — MNT group (members of the national team) which included athletes that did not have similar achievements (n = 59). The following biochemical parameters were studied: urea, creatine kinase, ALT, AST, testosterone, cortisol, anabolic index (AI).Results: the absolute values of all metabolites in the examined athletes were within the reference intervals. Statistically significant differences in most of the biochemical parameters were revealed between the compared groups in terms of the level of sports achievements. The SHA group showed a statistically significant shift in relation to MNT group, in direction of increasing the level of metabolites that characterize the predominance of anabolic processes — ALT, testosterone, AI. Metabolite levels, increase which reflects catabolic processes activity and inadequate or insufficient adaptation processes, in the SHA group were significantly lower than in the MNT group. The above changes of the absolute values of biochemical parameters were confirmed by correlation analysis.Conclusions: the obtained results allow us to state the optimal adaptation of this sport, the adequacy of metabolic processes in the group of highly qualified athletes.

Ant nests as a microbial hot spots in a long-term heavy metal-contaminated soils

Interactions between soil fauna and soil microorganisms are not fully recognized, especially in extreme environments, such as long-term metal-polluted soils. The purpose of the study was to assess how the presence of Lasius niger ants affected soil microbial characteristics in a long-term metal-polluted area (Upper Silesia in Poland). Paired soil samples were taken from bulk soil and from ant nests and analysed for a range of soil physicochemical properties, including metal content (zinc, cadmium, and lead). Microbial analysis included soil microbial activity (soil respiration rate), microbial biomass (substrate-induced respiration rate), and bacteria catabolic properties (Biolog® ECO plates). Soil collected from ant nests was drier and was characterized by a lower content of organic matter, carbon and nitrogen contents, and also lower metal content than bulk soil. Soil microbial respiration rate was positively related to soil pH (p = 0.01) and negatively to water-soluble metal content, integrated into TIws index (p = 0.01). Soil microbial biomass was negatively related to TIws index (p = 0.04). Neither soil microbial activity and biomass nor bacteria catabolic activity and diversity indices differed between bulk soil and ant nests. Taken together, ant activity reduced soil contamination by metals in a microscale which support microbial community activity and biomass but did not affect Biolog® culturable bacteria.

Human amniotic membrane modulates Wnt/β-catenin and NF-κβ signaling pathways in articular chondrocytes in vitro

ObjectiveInflammation, catabolism, and hypertrophy in chondrocytes play a central role in osteoarthritis (OA). The Wnt/β-catenin and NF-κβ pathways contribute to these degradative processes. This in vitro study evaluates the inhibitory effect of a novel therapeutic, micronized dehydrated human amnion/chorion membrane (μdHACM), as a potential treatment to offset elevated Wnt/β-catenin and NF-κβ signaling. DesignThree-dimensional human articular chondrocyte pellets were stimulated with an inflammatory cocktail to induce a degenerative phenotype. Treatments included varying doses of μdHACM. Protein and gene expression were analyzed using qRT-PCR, immunoblotting, and immunofluorescence to assess changes in the major constituents of Wnt/β-catenin and NF-κβ signaling. Regulation of catabolic activity was evaluated using enzymatic assays that detect MMP-13 and aggrecanase-mediated degradation products in conditioned media. ResultsConfirmation of the model was established through the expression of specific markers and extracellular matrix genes, verifying a chondrogenic phenotype was maintained. Inflammatory stimulation elicited a change in the chondrocyte proteome and secretome, elevating Wnt/β-catenin and NF-κβ signaling and downstream expression of inflammatory, proteolytic, and hypertrophic markers, while decreasing primary cartilage matrix components, ACAN and COL2A1. μdHACM reversed these inflammatory-induced changes, suppressing phospho-GSK-3β, β-catenin expression/nuclear localization of the Wnt signaling axis and inhibiting IKKβ, phospho-IκBα, and phospho-p65 in the NF-κβ signaling cascade. Additionally, μdHACM altered expression of direct downstream targets, namely MCP1, MMP3, MMP13, ADAMTS4, ADAMTS5, RUNX2 and COL10A1. Moreover, μdHACM reduced MMP-13 and aggrecanase-mediated substrate degradation. ConclusionμdHACM ameloriated the effects of inflammatory-induced degeneration in chondrocytes through Wnt/β-catenin and NF-κβ inhibition, subsequently downregulating key inflammatory, hypertrophic and catabolic mediators in vitro.

Abstract P388: Extra-cardiac BCAA Catabolism Lowers Blood Pressure And Protects From Heart Failure

Pharmacologic activation of branched chain amino acid (BCAA) catabolism is protective in numerous models of heart failure (HF). How this protection occurs has remained unclear, although a causative block in cardiac BCAA oxidation has been proposed. We use here in vivo heavy isotope infusion studies to show that cardiac preference for BCAA oxidation increases, rather than decreases, in multiple models of HF. We use various genetic models to show that cardiac-specific activation of BCAA oxidation does not protect from HF, even though systemic activation of BCAA oxidation does. Lowering plasma and cardiac BCAAs by genetic means is also not sufficient to confer protection comparable to that conferred by pharmacologic activation of BCAA oxidation, suggesting alternative mechanisms of protection. Surprisingly, telemetry and invasive hemodynamic studies showed that pharmacological activation of BCAA catabolism lowers blood pressure, a well-established cardioprotective mechanism. The effects on blood pressure occurred independently of nitric oxide (NO), and reflected a vascular resistance to adrenergic constriction. Finally, mendelian randomization studies revealed that elevations in plasma BCAAs portend higher blood pressure in large human cohorts. Together, these data indicate that activation of BCAA oxidation lowers blood pressure and protects from heart failure independently of any direct effects on the heart itself.

Mitochondrial-derived compartments: A “fusel alcohol generator” in yeast?

Schuler etal. (2021) demonstrate that mitochondrial-derived compartments protect cells from amino acid toxicity by activation of amino acid catabolism through the Ehrlich pathway, thus highlighting the incredible plasticity of mitochondria in rewiring cellular metabolism.

Single-cell RNA-seq reveals functionally distinct biomaterial degradation-related macrophage populations

Macrophages play crucial roles in host tissue reaction to biomaterials upon implantation in vivo. However, the complexity of biomaterial degradation-related macrophage subpopulations that accumulate around the implanted biomaterials in situ is not fully understood. Here, using single cell RNA-seq, we analyze the transcriptome profiles of the various cell types around the scaffold to map the scaffold-induced reaction, in an unbiased approach. This enables mapping of all biomaterial degradation-associated cells at high resolution, revealing distinct subpopulations of tissue-resident macrophages as the major cellular sources of biomaterial degradation in situ. We also find that scaffold architecture can affect the mechanotransduction and catabolic activity of specific material degradation-related macrophage subpopulations in an Itgav-Mapk1-Stat3 dependent manner, eventually leading to differences in scaffold degradation rate in vivo. Our work dissects unanticipated aspects of the cellular and molecular basis of biomaterial degradation at the single-cell level, and provides a conceptual framework for developing functional tissue engineering scaffolds in future.

Protease Activated Receptors and Arthritis.

The catabolic and destructive activity of serine proteases in arthritic joints is well known; however, these enzymes can also signal pain and inflammation in joints. For example, thrombin, trypsin, tryptase, and neutrophil elastase cleave the extracellular N-terminus of a family of G protein-coupled receptors and the remaining tethered ligand sequence then binds to the same receptor to initiate a series of molecular signalling processes. These protease activated receptors (PARs) pervade multiple tissues and cells throughout joints where they have the potential to regulate joint homeostasis. Overall, joint PARs contribute to pain, inflammation, and structural integrity by altering vascular reactivity, nociceptor sensitivity, and tissue remodelling. This review highlights the therapeutic potential of targeting PARs to alleviate the pain and destructive nature of elevated proteases in various arthritic conditions.

Reactive Astrocytosis in a Mouse Model of Chronic Polyamine Catabolism Activation.

Background: In the brain, polyamines are mainly synthesized in neurons, but preferentially accumulated in astrocytes, and are proposed to be involved in neurodegenerative/neuroinflammatory disorders and neuron injury. A transgenic mouse overexpressing spermine oxidase (SMOX, which specifically oxidizes spermine) in the neocortex neurons (Dach-SMOX mouse) was proved to be a model of increased susceptibility to excitotoxic injury. Methods: To investigate possible alterations in synapse functioning in Dach-SMOX mouse, both cerebrocortical nerve terminals (synaptosomes) and astrocytic processes (gliosomes) were analysed by assessing polyamine levels, ezrin and vimentin content, glutamate AMPA receptor activation, calcium influx, and catalase activity. Results: The main findings are as follows: (i) the presence of functional calcium-permeable AMPA receptors in synaptosomes from both control and Dach-SMOX mice, and in gliosomes from Dach-SMOX mice only; (ii) reduced content of spermine in gliosomes from Dach-SMOX mice; and (iii) down-regulation and up-regulation of catalase activity in synaptosomes and gliosomes, respectively, from Dach-SMOX mice. Conclusions: Chronic activation of SMOX in neurons leads to major changes in the astrocyte processes including reduced spermine levels, increased calcium influx through calcium-permeable AMPA receptors, and stimulation of catalase activity. Astrocytosis and the astrocyte process alterations, depending on chronic activation of polyamine catabolism, result in synapse dysregulation and neuronal suffering.

A review of the operating parameters on the microbial fuel cell for wastewater treatment and electricity generation.

Environmental and economic considerations suggest a more efficient and comprehensive use of biomass for bioenergy production. One of the most attractive technologies is the microbial fuel cell using the catabolic activity of microorganisms to generate electricity from organic matter. The microbial fuel cell (MFC) has operational benefits and higher performance than current technologies for producing energy from organic materials because it converts electricity from the substrate directly (at ambient temperature). However, MFCs are still not suitable for high energy demand due to practical limitations. The overall performance of an MFC depends on the electrode material, the reactor design, the operating parameters, substrates, and microorganisms. Furthermore, the optimization of the parameters will lead to the commercial development of this technology in the near future. The simultaneous effect of the parameters on each other (intensifier or attenuator) has also been investigated. The investigated parameters in this study include temperature, pH, flow rate and hydraulic retention time, mode, external resistance, and initial concentration.

Soil microbial activity along an altitudinal gradient: Vegetation as a main driver beyond topographic and edaphic factors

An altitudinal gradient in the mountains constitutes a unique ‘open-lab’ to examine environmental hypotheses and analyse the expected effects of global warming. The distribution of carbon (C)-, nitrogen (N)-, and phosphorus (P)-acquiring enzyme activity, microbial catabolic activity as represented by a community-level physiological profile (CLPP), and microbial functional diversity (HCLPP) within mountainous ecosystems consisting of mixed, fir and deciduous forests, as well as subalpine and alpine meadows (1260–2480 m a.s.l., Mt. Tkachiha, the Northwest Caucasus, Russia) has been studied. Concerning potential drivers, vegetation (plant projective cover, plant functional group composition, plant richness and diversity) and edaphic (soil nutrients: total and available C and N, total P, pH, texture, temperature, microbial biomass C) and topographic (elevation, slope, mean annual temperature calculated using biannual monitoring data) properties have been considered. The distribution patterns of the studied hydrolytic enzymes along an altitudinal gradient cannot be explained solely by elevation change and soil nutrient content. The activity of soil leucine aminopeptidase depends on vegetation type and graminoid abundance. β-D-glucosidase activity was mainly driven by the quality of soil organic matter (SOM), demonstrating a significant relation with the soil C:N ratio. The chitinase and phosphatase turned out soil temperature-sensitive enzymes. The CLPP depends on the available N content in the soil. The HCLPP distribution with altitude was driven by available N and forbs abundance represented by the widest spectrum of plant families and species. An altitudinal gradient determines the spread of the vegetation zone. In turn, vegetation properties, such as plant functional group composition, species richness and diversity, play a significant role in the distribution of soil microbial activity along an altitudinal gradient that controls the decomposition of SOM and nutrient cycling. Thus, the significant role of vegetation in the distribution of soil microbial activity across a wide range of natural ecosystems and in consideration of topographic and edaphic factors has been demonstrated.

The metabolic footprint of Clostridia and Erysipelotrichia reveals their role in depleting sugar alcohols in the cecum

BackgroundThe catabolic activity of the microbiota contributes to health by aiding in nutrition, immune education, and niche protection against pathogens. However, the nutrients consumed by common taxa within the gut microbiota remain incompletely understood.MethodsHere we combined microbiota profiling with an un-targeted metabolomics approach to determine whether depletion of small metabolites in the cecum of mice correlated with the presence of specific bacterial taxa. Causality was investigated by engrafting germ-free or antibiotic-treated mice with complex or defined microbial communities.ResultsWe noted that a depletion of Clostridia and Erysipelotrichia from the gut microbiota triggered by antibiotic treatment was associated with an increase in the cecal concentration of sugar acids and sugar alcohols (polyols). Notably, when we inoculated germ-free mice with a defined microbial community of 14 Clostridia and 3 Erysipelotrichia isolates, we observed the inverse, with a marked decrease in the concentrations of sugar acids and polyols in cecal contents. The carbohydrate footprint produced by the defined microbial community was similar to that observed in gnotobiotic mice receiving a cecal microbiota transplant from conventional mice. Supplementation with sorbitol, a polyol used as artificial sweetener, increased cecal sorbitol concentrations in antibiotic-treated mice, which was abrogated after inoculation with a Clostridia isolate able to grow on sorbitol in vitro.ConclusionsWe conclude that consumption of sugar alcohols by Clostridia and Erysipelotrichia species depletes these metabolites from the intestinal lumen during homeostasis.2LiAPNZ26g1fHk281rUPSMVideo abstract

Soil enzyme responses to land use change in the tropical rainforest of the Colombian Amazon region.

Soil enzymes mediate key processes and functions of the soils, such as organic matter decomposition and nutrient cycling in both natural and agricultural ecosystems. Here, we studied the activity of five extracellular soil enzymes involved in the C, N, and P-mineralizing process in both litter and surface soil layer of rainforest in the northwest region of the Colombian Amazon and the response of those soil enzymes to land use change. The experimental study design included six study sites for comparing long-term pasture systems to native forest and regeneration practices after pasture, within the main landscapes of the region, mountain and hill landscapes separately. Results showed considerable enzymatic activity in the litter layer of the forest, highlighting the vital role of this compartment in the nutrient cycling of low fertility soils from tropical regions. With the land use transition to pastures, changes in soil enzymatic activities were driven by the management of pastures, with SOC and N losses and reduced absolute activity of soil enzymes in long-term pastures under continuous grazing (25 years). However, the enzyme activities expressed per unit of SOC did not show changes in C and N-acquiring enzymes, suggesting a higher mineralization potential in pastures. Enzymatic stoichiometry analysis indicated a microbial P limitation that could lead to a high catabolic activity with a potential increase in the use of SOC by microbial communities in the search for P, thus affecting soil C sequestration, soil quality and the provision of soil-related ecosystem services.

4-Methylumbelliferone suppresses catabolic activation in anterior cruciate ligament-derived cells via a mechanism independent of hyaluronan inhibition

BackgroundThe anterior cruciate ligament (ACL) has a key role as a dynamic stabilizer of the knee joints, and ACL dysfunction caused by traumatic or degenerative rupture accelerates osteoarthritis progression. Thus, it is important to prevent the degenerative rupture of the ACL. 4-Methylumbelliferone (4-MU), a pre-approved drug, exerts anti-inflammatory effects in osteoarthritis chondrocytes. It was originally used as an inhibitor of hyaluronan synthesis in chondrocytes.MethodsIn this study, we investigated whether 4-MU affects the expression of catabolic factors, such as matrix metalloproteinase (MMP)-1, MMP-3, and interleukin (IL)-6, in ACL-derived cells and ACL explant cultures using immunohistochemistry, real-time RT-qPCR, and capillary western immunoassay. Furthermore, the hyaluronan concentration was evaluated using a colorimetric assay. Statistical analyses were conducted using analysis of variance for multi-group comparisons, followed by Tukey or Tukey-Kramer post hoc test.ResultsOur results revealed, for the first time, that 4-MU suppressed the IL-β-induced upregulation of pro-catabolic factors, such as MMP-1, MMP-3, and IL-6, in ACL-derived cells. This suppressive effect was also observed in the cultured ligament tissues in ex vivo experiments. 4-MU also reversed an enhanced dependence on glycolysis in IL-1β-activated ACL-derived cells. Furthermore, we found that the suppressive effects of 4-MU were exerted directly and not through the inhibition of hyaluronan synthesis.ConclusionsWe conclude that 4-MU could be an effective and useful treatment for knee osteoarthritis, owing to its anti-inflammatory effect on, not only chondrocytes but also on ligament cells.

Inhibition of heat shock protein (HSP) 90 reverses signal transducer and activator of transcription (STAT) 3-mediated muscle wasting in cancer cachexia mice.

Cancer cachexia is a common cause of death among cancer patients with no currently effective treatment available. In animal models, aberrant activation of STAT3 in skeletal muscle contributes to muscle wasting. However, clinically the factors regulating STAT3 activation and the molecular mechanisms involved remain incompletely understood. The expression of HSP90 and the activation of STAT3 were detected in muscle from the patients with cancer cachexia or the tumour-bearing cachectic mice. HSP90 inhibitors, including 17DMAG (alvespimycin) and PU-H71, were administered to cachexic mice and cachexia parameters, weight loss, food intake, survival rate, body composition, serum metabolites, muscle wasting pathology and catabolic activation were analysed. The co-culture of C2C12 myotube cells with C26 conditioned media was performed to investigate the pathological mechanism involved in catabolic muscle wasting. The roles of HSP90, STAT3 and FOXO1 in myotube atrophy were explored via overexpression or knockdown. An enhanced interaction between activated STAT3 and HSP90 in the skeletal muscle of cancer cachexia patients, is a crucial for the development of cachectic muscle wasting. HSP90 inhibitors 17DMAG and PU-H71 alleviated the muscle wasting in C26 and models or the myotube atrophy of C2C12 cells induced by C26 conditional medium. Prolonged STAT3 activation transactivated FOXO1 by binding directly to its promoter and triggered the muscle wasting in a FOXO1-dependent manner in muscle cells. The HSP90/STAT3/FOXO1 axis plays a critical role in cachectic muscle wasting, which might be a potential therapeutic target for the treatment of cancer cachexia.

The Pivotal Role of PAO in CDK Inhibitors (Roscovitine and Purvalanol)- Triggered Apoptosis in PUMA Null HCT116 Colon Cancer Cells

Background: Cycline-dependent kinase inhibitors (CDKi); roscovitine and purvalanol, are promising anti-cancer drugs due to their strong anti-proliferative effectiveness due to activation of PA catabolism. Besides transforming acetylated spermine and spermidine into spermidine and putrescine, respectively, polyamine oxidase (PAO) also generates hydrogen peroxide in high concentrations as a by-product. PAO was assumed as a pivotal key molecule during drug-induced apoptosis in cancer cells. Our aim is to reveal the role of PAO action in CDKi-triggered apoptosis in Puma knock-out HCT116 colon cancer cells. Methods: HCT116 wt and HCT116 Puma-/- cells were treated with Roscovitine and Purvalanol and cell viability and apoptosis were determined. Protein was isolated from treated and untreated cells and key molecules of cell cycle control and polyamine pathways were investigated at translational level. Polyamine content was determined by HPLC for all conditions. MDL-72527 was used as a PAO inhibitor and apoptotic cell death was analysed. Results: Roscovitine and purvalanol induced apoptosis and increased the cytotoxic responses in HCT116 wt and HCT116 Puma-/- colon carcinoma cell lines by modulating CDK1, 4, cyclin-B1, D3. Both, CDKi altered intrinsic apoptotic pathways in HCT116 wt. Whereas, drug-induced apoptosis occurred caspase-independent in Puma-/- colon cancer cells. Roscovitine and purvalanol up-regulated polyamine catabolic enzymes, whereas CDK inhibitors decreased the polyamine levels in HCT116 wt and HCT116 Puma-/- colon cancer cells. In addition, PAO inhibitor MDL72527 prevented drug-induced apoptosis. Conclusion: PAO expression profile might be a critical target in CDK inhibitors-triggered apoptosis in HCT116 colorectal cancer cells. Thus, MAPK signaling pathway relations with cell cycle and polyamine catabolic pathway investigations are in progress.

Catabolic enzyme activity and kinetics of pyrene degradation by novel bacterial strains isolated from contaminated soil

Polycyclic aromatic hydrocarbons (PAHs) with high molecular weight are difficult to degrade owing to their chemical structure and stability. This study reports degradation of pyrene by two potent Gram-positive bacterial strains isolated from petroleum-contaminated soil from Bijwasan supply location of Bharat Petroleum Corporation Limited (BPCL), India. The bacteria were identified as Kocuria flava and Rhodococcus pyridinivorans based on 16S rRNA gene sequencing. The degradation of pyrene, enzyme activity of Catechol 2,3-dioxygenase (C23O), dehydrogenase, and peroxidase, and the rate kinetics of degradation were investigated using the isolated bacteria. K. flava and R. pyridinivorans could degrade pyrene with an efficiency of 53.8% and 56.2%, within 15 days of incubation period under laboratory conditions. The consortium revealed 56.4% degradation of pyrene indicating that there is no significant synergistic/inhibitive effect. The activity (maximum on 9th day of incubation) of peroxidase enzyme (9.4 × 10 −4 and 16.9 × 10 −4 μ M/ml/min) was followed by dehydrogenase (2.6 × 10 −4 and 2.3 × 10 −4 μ M/ml/min) and C23O (2.2 × 10 −4 and 2.8 × 10 −4 μ M/ml/min) for K. flava and R. pyridinivorans , respectively, suggesting their involvement in ring-cleavage, diol-formation, and subsequent oxidation of the intermediates. Analysis of rate kinetics exhibited degradation of pyrene to be the first order reaction indicating that an increase in initial concentration of pyrene will not compromise with the ability of studied bacteria towards degradation. Analysis of initial and final concentration of treated media over HPLC confirmed significant pyrene degradation within 15 days. The study concludes that K. flava and R. pyridinivorans can play an active role in remediation of hydrocarbon-contaminated sites. • Degradation of pyrene by K. flava and R. pyridinivorans reported for first time. • C23O enzyme regulates ring cleavage and peroxidase oxidises pyrene-intermediates. • No inhibitory effect of K. flava and R. pyridinivorans over each other.

The Effect of a Lower Body Positive Pressure Supported Treadmill Exercise Regime on Systemic Biomarkers of Inflammation and Cartilage Degradation in Individuals with Knee Osteoarthritis: A Pilot Study

Background: Knee osteoarthritis (OA) has been linked to a chronic low-grade inflammatory response and altered metabolic activity of articular cartilage. Objective: The purpose of this investigation was to evaluate the effectiveness of a 12-week (3 times/week) lower body positive pressure (LBPP) treadmill walking regime on knee pain and systemic biomarkers of inflammation and cartilage degradation. Methods: Sixteen overweight (BMI > 25 kg/m2) knee OA patients were randomized to a LBPP treadmill walking exercise group (N = 7) or non-exercise control group (N = 9). Baseline and 12-week follow-up assessments evaluated the following dependent variables: acute knee pain during full weight bearing treadmill walking; inflammatory biomarkers (C-reactive protein, interleukin-1β, interleukin-6, s100A8/A9, and tumor necrosis factor-α), and catabolic metabolism of articular cartilage (sCOMP). Results: Knee pain at baseline and follow-up remained unchanged for the non-exercise control group (P > 0.05). However, knee pain for the LBPP exercise group was significantly decreased at follow-up (P ≤ 0.05). No differences in the biomarkers of inflammation and cartilage degradation were observed for between and within group comparisons (all P > 0.05). Conclusions: Data suggested that the LBPP supported walking regime could be effectively used to promote regular weight bearing exercise without exacerbation of knee joint pain and did not increase levels of systemic inflammation or catabolic activity of articular cartilage in overweight knee OA patients. This pilot investigation offers important insight regarding the potential role that the LBPP technology could play in facilitating investigations examining the disease modifying effect of exercise on knee OA pathogenesis.

Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.

Tree species mixing affects soil microbial functioning indirectly via root and litter traits and soil parameters in European forests

Abstract Plant community composition influences soil microbial communities through plant trait variations that lead to changes in nutrient and organic carbon inputs into the soil by root exudates and plant litter. Although plant litter and living roots are known to influence microbial functioning independently, their relative effects are rarely measured simultaneously in naturally occurring plant communities. Here, we sought to evaluate how forest floor litter and absorptive roots affect broad functions of soil microbial communities, and how this may be influenced by tree species mixing. To do so, forest floor litter, absorptive roots and soil were sampled from mono‐specific and three‐species mixed stands in four mature, natural forest ecosystems across Europe. The direct effects of tree species mixing, its indirect effects via litter and root traits, and the effects of soil parameters on microbial biomass, catabolic activity and diversity, and denitrification were analysed. Results did not show direct tree mixture effects on the soil microbial parameters we measured but did suggest indirect influences via tree mixture effects on traits of above‐ground litter and absorptive roots and soil parameters. Mixed forests composed of any three tree species modified soil microbial functioning by influencing nutrient availability in forest floor litter and root resource acquisition. Tree mixing also modified soil microbial functioning and catabolic diversity by influencing soil fertility and physicochemical properties. Our findings suggest an indirect but present influence of tree species mixing on the activity of heterotrophic soil microbial communities across four different forest ecosystems ranging from Mediterranean to boreal forests. Our study contributes to a better mechanistic understanding of mixed tree species effects on soil microbial functioning via the modification of forest floor litter properties and traits of absorptive roots represented by the tree community beyond simple species number consideration, and potentially via soil properties. A free Plain Language Summary can be found within the Supporting Information of this article.

Regulation of metabolic homeostasis by the TGF-β superfamily receptor ALK7.

ALK7 (Activin receptor-like kinase 7) is a member of the TGF-β receptor superfamily predominantly expressed by cells and tissues involved in endocrine functions, such as neurons of the hypothalamus and pituitary, pancreatic β-cells and adipocytes. Recent studies have begun to delineate the processes regulated by ALK7 in these tissues and how these become integrated with the homeostatic regulation of mammalian metabolism. The picture emerging indicates that ALK7's primary function in metabolic regulation is to limit catabolic activities and preserve energy. Aside of the hypothalamic arcuate nucleus, the function of ALK7 elsewhere in the brain, particularly in the cerebellum, where it is abundantly expressed, remains to be elucidated. Although our understanding of the basic molecular events underlying ALK7 signaling has benefited from the vast knowledge available on TGF-β receptor mechanisms, how these connect to the physiological functions regulated by ALK7 in different cell types is still incompletely understood. Findings of missense and nonsense variants in the Acvr1c gene, encoding ALK7, of some mouse strains and human subjects indicate a tolerance to ALK7 loss of function. Recent discoveries suggest that specific inhibitors of ALK7 may have therapeutic applications in obesity and metabolic syndrome without overt adverse effects.