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By using carbon dioxide (CO2) as carbon source, fossil sources can be replaced. In microbial electrosynthesis (MES), CO2 and in situ produced hydrogen (H2) are used for bacterial biofilm growth.Kyrpidia spormannii is a Knallgas bacterium with a protein content of 61% of its dry mass. It grows as a biofilm on the cathode in an oxic MES. The biomass can be used for the food and feed industry.A continuous process was established by applying a negative potential to harvest parts of the biofilm for use. The biofilm regenerated after being partly harvested.The system was operated at maximum coulombic efficiency, enabling the energy input to be minimized.A numerical model describing the growth of K. spormannii as a H2-oxidizing bacterium in an oxic MES system was developed. This helps predict growth behavior and efficiencies for further optimization. Autotrophic microbial electrosynthesis (MES) processes are mainly based on organisms that rely on carbon dioxide (CO2) as an electron acceptor and typically have low biomass yields. However, there are few data on the process and efficiencies of oxic MES (OMES). In this study, we used the knallgas bacterium Kyrpidia spormannii to investigate biomass formation and energy efficiency of cathode-dependent growth. The study revealed that the process can be carried out with the same electron efficiency as conventional gas fermentation, but overcomes disadvantages, such as the use of explosive gas mixtures. When accounting only for the electron input via electrical energy, a solar energy demand of 67.89 kWh kg–1 dry biomass was determined. While anaerobic MES is ideally suited to produce methane, short-chain alcohols, and carboxylic acids, its aerobic counterpart could extend this important range of applications to not only protein for use in the food and feed sector, but also further complex products. [Display omitted] Oxic microbial electrosynthesis (OMES) using Kyrpidia spormannii can match the electron efficiency of gas fermentation, without producing explosive gas mixtures. It uses solar energy efficiently and has the potential to produce complex products, such as proteins, for food and feed instead of methane and alcohols, which are typical products of anoxic MES. Oxic microbial electrosynthesis (OMES) is a relatively new technology, particularly in the context of biofilm-based processes, which is now achieving a Technology Readiness Level (TRL) of 3 in laboratory reactors. Similar to other biofilm-based technologies, OMES faces both challenges and opportunities. One of the primary challenges will be identifying a reactor design that maximizes electrode surface area while simultaneously maintaining a predictable fluidic regime. Since OMES relies on an electrochemical system, reactor configuration must also minimize electrochemical losses. If biomass is intended to be the end product, it is important to consider that, over the duration of the experiment, microorganisms are likely to adapt to the changing process conditions, potentially enabling evolution-based optimization of biocatalysts. In the future, OMES is likely to compete with processes relying on anaerobic gas fermentation as a first step and subsequent usage of end products from this first step as feed for a second reaction step likely involving aerobic microorganisms. Full economic and ecological process assessment based on larger scale reactors will be necessary to decide under which circumstances which technology might be superior.

Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo. Moreover, we analysed the molecular mechanisms involved and observed an antagonistic effect between Ca2+ and BMP-2 on SMAD1/5, ERK and S6K signalling after 24 hours. More importantly, a cooperative effect between Ca2+ and BMP-2 on the phosphorylation of SMAD1/5, S6, GSK3 and total levels of β-CATENIN was observed at a later differentiation time (10 days). Furthermore, Ca2+ alone favoured the phosphorylation of SMAD1, which correlates with the induction of Bmp2 and Bmp4 gene expression. These data suggest that Ca2+ and BMP-2 cooperate and promote an autocrine/paracrine osteogenic feed-forward loop. On the whole, these results demonstrate the usefulness of calcium-based bone grafts or the addition of exogenous Ca2+ in bone tissue engineering.

Sarcopenia, a subject of extensive research, has led to numerous clinical trials and systematic reviews (SR). These reviews aid healthcare professionals by summarizing results and conducting meta-analyses, enhancing reliability. However, the abundance of reviews complicates decision-making on sarcopenia management. To address this, SR of SR have emerged, consolidating data from various sources into comprehensive documents. To assess the isolated impact of dietary interventions on sarcopenia's diagnostic criteria for older individuals. A study protocol for a SR of SR, following Cochrane and PRISMA recommendations. The search strategy includes the MeSH 'sarcopenia' and its subheadings; 'aged' and its subheadings; 'nutrition' and its subheadings; and filter 'systematic review', performed at main databases. Selected studies must include older adults, submitted to nutritional interventions compared to control groups. Quantitative analyses will use inverse variance statistic method (random effects); the effect measures mean difference. Heterogeneity measured with Q-Test. The results of this SR of SR may provide valuable information about the sarcopenia treatment, deepening the knowledge about. This protocol is reproducible, requires low cost and personnel, and may allow a higher understanding on sarcopenia treatment and management on older people.

Dynamic muscle fascicle length measurements through B-mode ultrasound have become popular for the non-invasive physiological insights they provide regarding musculoskeletal structure-function. However, current practices typically require time consuming post-processing to track muscle length changes from B-mode images. A real-time measurement tool would not only save processing time but would also help pave the way toward closed-loop applications based on feedback signals driven by in vivo muscle length change patterns. In this paper, we benchmark an approach that combines traditional machine learning (ML) models with B-mode ultrasound recordings to obtain muscle fascicle length changes in real-time. To gauge the utility of this framework for 'in-the-loop' applications, we evaluate accuracy of the extracted muscle length change signals against time-series' derived from a standard, post-hoc automated tracking algorithm. We collected B-mode ultrasound data from the soleus muscle of six participants performing five defined ankle motion tasks: (a) seated, constrained ankle plantarflexion, (b) seated, free ankle dorsi/plantarflexion, (c) weight-bearing, calf raises (d) walking, and then a (e) mix. We trained machine learning (ML) models by pairing muscle fascicle lengths obtained from standardized automated tracking software (UltraTrack) with the respective B-mode ultrasound image input to the tracker, frame-by-frame. Then we conducted hyperparameter optimizations for five different ML models using a grid search to find the best performing parameters for a combination of high correlation and low RMSE between ML and UltraTrack processed muscle fascicle length trajectories. Finally, using the global best model/hyperparameter settings, we comprehensively evaluated training-testing outcomes within subject (i.e., train and test on same subject), cross subject (i.e., train on one subject, test on another) and within/direct cross task (i.e., train and test on same subject, but different task). Support vector machine (SVM) was the best performing model with an average r = 0.70 ±0.34 and average RMSE = 2.86 ±2.55 mm across all direct training conditions and average r = 0.65 ±0.35 and average RMSE = 3.28 ±2.64 mm when optimized for all cross-participant conditions. Comparisons between ML vs. UltraTrack (i.e., ground truth) tracked muscle fascicle length versus time data indicated that ML tracked images reliably capture the salient qualitative features in ground truth length change data, even when correlation values are on the lower end. Furthermore, in the direct training, calf raises condition, which is most comparable to previous studies validating automated tracking performance during isolated contractions on a dynamometer, our ML approach yielded 0.90 average correlation, in line with other accepted tracking methods in the field. By combining B-mode ultrasound and classical ML models, we demonstrate it is possible to achieve real-time tracking of human soleus muscle fascicles across a number of functionally relevant contractile conditions. This novel sensing modality paves the way for muscle physiology in-the-loop applications that could be used to modify gait via biofeedback or unlock novel wearable device control techniques that could enable restored or augmented locomotion performance.

The HERC gene family encodes proteins with two characteristic domains in their sequence: the HECT domain and the RCC1-like domain (RLD). In humans, the HERC family comprises six members that can be divided into two groups based on their molecular mass and domain structure. Whereas large HERCs (HERC1 and HERC2) contain one HECT and more than one RLD, small HERCs (HERC3-6) possess single HECT and RLD domains. Accumulating evidence shows the HERC family proteins to be key components of a wide range of cellular functions, including neurodevelopment, DNA damage repair, cell growth and immune response. Considering the significant recent advances made regarding HERC functionality, an updated review summarizing the progress is greatly needed at 10 years since the last HERC review. We provide an integrated view of HERC function and go into detail about its implications for several human diseases such as cancer and neurological disorders.

Muscle quality is an important component of the functional profile of the elderly, and previous studies have shown that both muscle quantity and quality independently contribute to muscle strength of the elderly. This study aimed to verify the association between quadriceps femoris muscle quality, analyzed by specific tension and echo intensity (EI), and rate of torque development (RTD) of the knee extensor muscles with the functional performance in elderly active women. Forty-five healthy, active elderly women (70.28 ± 6.2) volunteered to participate in this study. Quadriceps femoris muscle thickness and EI were determined by ultrasonography. Knee extension isometric peak torque and RTD were obtained from maximal isometric voluntary contraction curves. The 30-s sit-to-stand-up (30SS) test and usual gait speed (UGS) test were applied to evaluate functional performance. Rectus femoris EI presented a significant negative correlation with 30SS ( r  = −0.505, P  < 0.01), UGS ( r s  = −0.347, P  < 0.05), and isometric peak torque ( r  = −0.314, P  < 0.05). The quadriceps femoris EI correlated negatively with 30SS ( r  = −0.493, P  < 0.01) and isometric peak torque ( r  = −0.409, P  < 0.01). The EI of the quadriceps femoris and all quadriceps muscle portions significantly correlated with RTD. RTD significantly correlated with physical performance in both functional tests (30SS =  r  = 0.340, P  < 0.05; UGS =  r s  = 0.371, P  < 0.05). We concluded that muscle EI may be an important predictor of functional performance and knee extensor power capacity in elderly, active women.

Background Older individuals present reductions in muscle mass and physical function, as well as a blunted muscle protein synthesis response to amino acid administration and physical activity. Although resistance training is an effective intervention to slow down muscle impairments in the elderly, there is no consensus whether a combination with protein supplementation could offer additional benefits to an older population. Objective We aimed to systematically summarize and quantify whether protein supplementation could optimize the effects of resistance training on muscle mass and strength in an aged population. Design A structured literature search was conducted on MEDLINE (PubMed), Cochrane, EMBASE and LILACS databases. The search had no period or language restrictions. Inclusion criteria comprised study design (randomized controlled trials—RCTs), sample mean age (60 years and over) and intervention (a resistance training program for a period of 6 weeks or longer combined with protein or amino acids supplementation). Two independent reviewers performed the study selection and data extraction. Continuous data on fat-free mass, muscle mass and muscle strength were pooled using a random-effects model. Results Of the 540 articles reviewed, 29 eligible articles underwent full-text evaluation. Nine RCTs (462 subjects) met the inclusion criteria and were included in the study. The mean age of the participants ranged from 61 to 79 years old. Protein supplementation protocols varied widely throughout the studies. Three studies used quantities related to the body mass of the participants and the other six trials provided supplements in daily amounts, independently of subjects’ body masses. Overall, protein supplementation in combination with resistance training was associated with gains in fat-free mass, resulting in a standardized mean difference (SMD) of 0.23 [95 % confidence interval (CI), 0.05–0.42]. However, protein supplementation was not associated with changes in muscle mass (0.14, 95 % CI −0.05 to 0.32) or muscle strength (0.13, 95 % CI −0.06 to 0.32). Limitations Studies among the very elderly population are scarce. The variation regarding the supplementation protocol, namely the different protein sources, amounts and timing of ingestion, also made it harder to compare the results. The general quality of the studies was low, reflecting increased risk of bias in some studies. Despite these limitations, this systematic review provides a general overview of the role of protein supplementation with no other added macronutrients to augment muscle mass and strength during resistance training in older adults. Conclusion Combining protein supplementation with resistance training is effective for eliciting gains in fat-free mass among older adults, but does not seem to increase muscle mass or strength.

Considering works published in the literature for more than a decade (period from January 2008 till June 2019), this paper provides an overview of recent applications of the so-called “solar furnaces”, their reactors, process chambers and related devices, aiming specifically at the processing of (solid) materials. Based on the author’s own experience, some prospects on future trends are also presented. The aim of this work is to demonstrate the tremendous potentialities of the usage of solar heat for materials processing, but also to reveal the necessity of further developing solar-driven high-temperature technologies (which are required to displace the use of electricity or natural gas). In particular, it is essential to improve the temperature homogeneity conditions inside reaction chambers for materials processing using solar heat. Moreover, new innovative modular systems, practical and flexible, for capture, concentration, control and conduction of concentrated solar radiation are suggested. Solar thermal technologies for the production of electricity, as well as solar thermochemical processes for production of gases or liquids, are outside the scope of this review.

Osteoblast differentiation is achieved by activating a transcriptional network in which Dlx5 , Runx2 and Osx/SP7 have fundamental roles. The tumour suppressor p53 exerts a repressive effect on bone development and remodelling through an unknown mechanism that inhibits the osteoblast differentiation programme. Here we report a physical and functional interaction between Osx and p53 gene products. Physical interaction was found between overexpressed proteins and involved a region adjacent to the OSX zinc fingers and the DNA-binding domain of p53. This interaction results in a p53-mediated repression of OSX transcriptional activity leading to a downregulation of the osteogenic programme. Moreover, we show that p53 is also able to repress key osteoblastic genes in Runx2 -deficient osteoblasts. The ability of p53 to suppress osteogenesis is independent of its DNA recognition ability but requires a native conformation of p53, as a conformational missense mutant failed to inhibit OSX. Our data further demonstrates that p53 inhibits OSX binding to their responsive Sp1/GC-rich sites in the promoters of their osteogenic target genes, such as IBSP or COL1A1 . Moreover, p53 interaction to OSX sequesters OSX from binding to DLX5. This competition blocks the ability of OSX to act as a cofactor of DLX5 to activate homeodomain-containing promoters. Altogether, our data support a model wherein p53 represses OSX–DNA binding and DLX5–OSX interaction, and thereby deregulates the osteogenic transcriptional network. This mechanism might have relevant roles in bone pathologies associated to osteosarcomas and ageing.

Heterotopic ossification (HO) is the pathological formation of ectopic endochondral bone within soft tissues. HO occurs following mechanical trauma, burns, or congenitally in patients suffering from fibrodysplasia ossificans progressiva (FOP). FOP patients carry a conserved mutation in ACVR1 that becomes neomorphic for activin A responses. Here, we demonstrate the efficacy of BYL719, a PI3Kα inhibitor, in preventing HO in mice. We found that PI3Kα inhibitors reduce SMAD, AKT, and mTOR/S6K activities. Inhibition of PI3Kα also impairs skeletogenic responsiveness to BMPs and the acquired response to activin A of the Acvr1 R206H allele. Further, the efficacy of PI3Kα inhibitors was evaluated in transgenic mice expressing Acvr1 Q207D . Mice treated daily or intermittently with BYL719 did not show ectopic bone or cartilage formation. Furthermore, the intermittent treatment with BYL719 was not associated with any substantial side effects. Therefore, this work provides evidence supporting PI3Kα inhibition as a therapeutic strategy for HO. Synopsis Heterotopic ossification is a pathological process of endochondral bone formation at extraskeletal sites. Clinical therapy is now limited to symptomatic treatments. This study proposes PI3Kα inhibitors as a potential therapeutic strategy for heterotopic ossification. PI3Kα inhibitors reduce the specification of mesenchymal progenitors into skeletal lineages. PI3Kα inhibition with BYL719 was effective at suppressing heterotopic ossification in vivo . Intermittent treatment with BYL719 was not associated with substantial side effects. Graphical Abstract Heterotopic ossification is a pathological process of endochondral bone formation at extraskeletal sites. Clinical therapy is now limited to symptomatic treatments. This study proposes PI3Kα inhibitors as a potential therapeutic strategy for heterotopic ossification.