Regulation of Muscle Glycogen Metabolism during Exercise: Implications for Endurance Performance and Training Adaptations.

Since the introduction of the muscle biopsy technique in the late 1960s, our understanding of the regulation of muscle glycogen storage and metabolism has advanced considerably. Muscle glycogenolysis and rates of carbohydrate (CHO) oxidation are affected by factors such as exercise intensity, duration, training status and substrate availability. Such changes to the global exercise stimulus exert regulatory effects on key enzymes and transport proteins via both hormonal control and local allosteric regulation. Given the well-documented effects of high CHO availability on promoting exercise performance, elite endurance athletes are typically advised to ensure high CHO availability before, during and after high-intensity training sessions or competition. Nonetheless, in recognition that the glycogen granule is more than a simple fuel store, it is now also accepted that glycogen is a potent regulator of the molecular cell signaling pathways that regulate the oxidative phenotype. Accordingly, the concept of deliberately training with low CHO availability has now gained increased popularity amongst athletic circles. In this review, we present an overview of the regulatory control of CHO metabolism during exercise (with a specific emphasis on muscle glycogen utilization) in order to discuss the effects of both high and low CHO availability on modulating exercise performance and training adaptations, respectively

Multiomic features associated with mucosal healing and inflammation in paediatric Crohn's disease

Background The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD). Aim To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD. Methods Twenty‐five participants aged 3‐18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin 100 μg/g, “mucosal inflammation,” n = 11). 16S gene‐based metataxonomics, 1H‐NMR spectroscopy‐based metabolic profiling and protease activity assays were performed on stool samples. Results Relative abundance of Dialister species was six times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine‐learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35‐times greater in the low calprotectin group (95% CI 1.03‐1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54‐times greater in the high calprotectin group (95% CI 1.05‐2.03, P = 0.028). Conclusions This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with “mucosal healing.” It supports further investigation of these as potential novel therapeutic targets in CD

On the Complex Network Structure of Musical Pieces: Analysis of Some Use Cases from Different Music Genres

This paper focuses on the modeling of musical melodies as networks. Notes of a melody can be treated as nodes of a network. Connections are created whenever notes are played in sequence. We analyze some main tracks coming from different music genres, with melodies played using different musical instruments. We find out that the considered networks are, in general, scale free networks and exhibit the small world property. We measure the main metrics and assess whether these networks can be considered as formed by sub-communities. Outcomes confirm that peculiar features of the tracks can be extracted from this analysis methodology. This approach can have an impact in several multimedia applications such as music didactics, multimedia entertainment, and digital music generation.Comment: accepted to Multimedia Tools and Applications, Springe

Terrestrial laser scanning survey in support of unstable slopes analysis. The case of Vulcano Island (Italy)

The capability to measure at distance dense cloud of 3D point has improved the relevance of geomatic techniques to support risk assessment analysis related to slope instability. This work focuses on quantitative analyses carried out to evaluate the effects of potential failures in the Vulcano Island (Italy). Terrestrial laser scanning was adopted to reconstruct the geometry of investigated slopes that is required for the implementation of numerical modeling adopted to simulate runout areas. Structural and morphological elements, which influenced past instabilities or may be linked to new events, were identified on surface models based on ground surveying. Terrestrial laser scanning was adopted to generate detailed 3D models of subvertical slopes allowing to characterize the distribution and orientation of the rock discontinuities that affect instability mechanism caused by critical geometry. Methods for obtaining and analyzing 3D topographic data and to implement simulation analyses contributing to hazard and risk assessment are discussed for two case studies (Forgia Vecchia slope and Lentia rock walls)

Real-Life Anti-Tumour Necrosis Factor Experience in > 500 Paediatric United Kingdom Inflammatory Bowel Disease Patients.

OBJECTIVES: To measure the effectiveness, safety and use of anti-Tumour necrosis Factor (TNF) therapy in paediatric inflammatory bowel disease (PIBD) in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment (PGA) +/or the Paediatric Crohn's Disease Activity Index (PCDAI). RESULTS: 37 centres participated (23 of 25 specialist PIBD sites). 524 patients were included; 429 Crohn's disease (CD), 76 ulcerative colitis (UC), 19 IBD unclassified (IBDU). 87% (488/562) anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (IQR 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by PGA compared to 41% (88/217) by PCDAI; Kappa (Κ) 0.28 = only 'fair agreement' (p < 0.001).Where documented, 77% (53/69) of CD patients responded to induction; and 65% (46/71) entered remission. 2287 infusions and 301.96 years of patient follow-up (n = 385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Perianal abscess drainage was less common after anti-TNF initiation (CD): 26% (27/102) before, 7% (3/42) after (p = 0.01); however pre and post anti-TNF data collection was not over equal time periods. CONCLUSION: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools which need to be addressed to improve ongoing patient care

Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli

Despite extensive study of individual enzymes and their organization into pathways, the means by which enzyme networks control metabolite concentrations and fluxes in cells remains incompletely understood. Here, we examine the integrated regulation of central nitrogen metabolism in Escherichia coli through metabolomics and ordinary-differential-equation-based modeling. Metabolome changes triggered by modulating extracellular ammonium centered around two key intermediates in nitrogen assimilation, α-ketoglutarate and glutamine. Many other compounds retained concentration homeostasis, indicating isolation of concentration changes within a subset of the metabolome closely linked to the nutrient perturbation. In contrast to the view that saturated enzymes are insensitive to substrate concentration, competition for the active sites of saturated enzymes was found to be a key determinant of enzyme fluxes. Combined with covalent modification reactions controlling glutamine synthetase activity, such active-site competition was sufficient to explain and predict the complex dynamic response patterns of central nitrogen metabolites

Deep analysis of perception through dynamic structures that emerge in cortical activity from self-regulated noise

The statistical properties of the spontaneous background electrocorticogram (ECoG) were modeled, starting with random numbers, constraining the distributions, and identifying characteristic deviations from randomness in ECoG from subjects at rest and during intentional behaviors. The ECoG had been recorded through 8 × 8 arrays of 64 electrodes, from the surfaces of auditory, visual, or somatic cortices of 9 rabbits, and from the inferotemporal cortex of a human subject. Power spectral densities (PSD) in coordinates of log10 power versus log10 frequency of ECoG from subjects at rest usually conformed to noise in power-law distributions in a continuum. PSD of ECoG from active subjects usually deviated from noise in having peaks in log10 power above the power-law line in various frequency bands. The analytic signals from the Hilbert transform after band pass filtering in the beta and gamma ranges revealed beats from interference among distributed frequencies in band pass filtered noise called Rayleigh noise. The beats were displayed as repetitive down spikes in log10 analytic power. Repetition rates were proportional to filter bandwidths for all center frequencies. Resting ECoG often gave histograms of the magnitudes and intervals of down spikes that conformed to noise. Histograms from active ECoG often deviated from noise in Rayleigh distributions of down spike intervals by giving what are called Rice (Mathematical analysis of random noise—and appendixes—technical publications monograph B-1589. Bell Telephone Labs Inc., New York, 1950) distributions. Adding power to noise as signals at single frequencies simulated those deviations. The beats in dynamic theory are deemed essential for perception, by gating beta and gamma bursts at theta rates through enhancement of the cortical signal-to-noise ratio in exceptionally deep down spikes called null spikes

Spectral action, Weyl anomaly and the Higgs-Dilaton potential

We show how the bosonic spectral action emerges from the fermionic action by the renormalization group flow in the presence of a dilaton and the Weyl anomaly. The induced action comes out to be basically the Chamseddine-Connes spectral action introduced in the context of noncommutative geometry. The entire spectral action describes gauge and Higgs fields coupled with gravity. We then consider the effective potential and show, that it has the desired features of a broken and an unbroken phase, with the roll down.Comment: 23 pages, 4 figure

Carbohydrate improves exercise capacity but does not affect subcellular lipid droplet morphology, AMPK and p53 signalling in human skeletal muscle

We examined the effects of carbohydrate (CHO) feeding on lipid droplet (LD) morphology, muscle glycogen utilisation and exercise‐induced skeletal muscle cell signalling. After a 36 h CHO loading protocol and pre‐exercise meal (12 and 2 g kg–1, respectively), eight trained males ingested 0, 45 or 90 g CHO h–1 during 180 min cycling at lactate threshold followed by an exercise capacity test (150% lactate threshold). Muscle biopsies were obtained pre‐ and post‐completion of submaximal exercise. Exercise decreased (P 0.05). Exercise decreased LD number within central and peripheral regions of both type I and IIa fibres, though reduced LD size was exclusive to type I fibres. Exercise induced (all P 0.05). CHO increased exercise capacity where 90 g h–1 (233 ± 133 s) > 45 g h–1 (156 ± 66 s; P = 0.06) > 0 g h–1 (108 ± 54 s; P = 0.03). In conditions of high pre‐exercise CHO availability, we conclude CHO feeding does not influence exercise‐induced changes in LD morphology, glycogen utilisation or cell signalling pathways with regulatory roles in mitochondrial biogenesis

Clinical Efficacy of Blue Light Full Body Irradiation as Treatment Option for Severe Atopic Dermatitis

BACKGROUND: Therapy of atopic dermatitis (AD) relies on immunosuppression and/or UV irradiation. Here, we assessed clinical efficacy and histopathological alterations induced by blue light-treatment of AD within an observational, non-interventional study. METHODOLOGY/PRINCIPAL FINDINGS: 36 patients with severe, chronic AD resisting long term disease control with local corticosteroids were included. Treatment consisted of one cycle of 5 consecutive blue light-irradiations (28.9 J/cm(2)). Patients were instructed to ask for treatment upon disease exacerbation despite interval therapy with topical corticosteroids. The majority of patients noted first improvements after 2-3 cycles. The EASI score was improved by 41% and 54% after 3 and 6 months, respectively (p≤0.005, and p≤0.002). Significant improvement of pruritus, sleep and life quality was noted especially after 6 months. Also, frequency and intensity of disease exacerbations and the usage of topical corticosteroids was reduced. Finally, immunohistochemistry of skin biopsies obtained at baseline and after 5 and 15 days revealed that, unlike UV light, blue light-treatment did not induce Langerhans cell or T cell depletion from skin. CONCLUSIONS/SIGNIFICANCE: Blue light-irradiation may represent a suitable treatment option for AD providing long term control of disease. Future studies with larger patient cohorts within a randomized, placebo-controlled clinical trial are required to confirm this observation