When does the influence of maturation on anthropometric and physical fitness characteristics increase and subside?

The relationships between maturation and anthropometric and physical performance characteristics are dynamic and often asynchronous; confounding the capability to accurately evaluate performance during adolescence. This study aimed to (i) examine the influence of chronological age (CA) and somatic maturation (YPHV) upon anthropometric and physical performance parameters, and (ii) identify the transition/change time points in these relationships using segmental regression. N = 969 soccer players (8-18 years of age) completed anthropometric and physical test assessments, including a countermovement jump (CMJ), agility T test, 10 and 20 m sprints, and multistage fitness test (MSFT). When modeled against CA and YPHV, results identified time point phases with increased rates of stature (CA-7.5, YPHV-8.6 cm/y at 10.7-15.2 years or -3.2 to +0.8 YPHV) and body mass gain (CA-7.1, YPHV-7.5 kg/y at 11.9-16.1 years or -1.6 to +4.0 YPHV), followed by gain reductions. Increased rates of sprint performance development (31%-43% gains) occurred at 11.8-15.8 CA or -1.8 to +1.2 YPHV, with gains subsiding thereafter. CMJ, T test, and MSFT gains appeared relatively linear with no change in developmental rate apparent. Developmental tempos did again, however, subside at circa (CMJ and T test) to post-PHV (MSFT). Based on our sample and analysis, periods of increased developmental rates (stature, mass, sprint) were apparent alongside progressive gains for other physical measures, before all subsided at particular age and maturation time points. Findings highlight dynamic asynchronous development of players, physical attributes, and the need to account for the influence of maturation on athletic performance until post-PHV

Mitochondrial ROS cause motor deficits induced by synaptic inactivity:implications for synapse pruning

Developmental synapse pruning refines burgeoning connectomes. The basic mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they select inactive synapses for pruning: whether they do so is unknown. To begin to unravel whether mitochondrial ROS regulate pruning, we made the local consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic inactivity increases mitochondrial ROS; and (2) antioxidants rescue synaptic inactivity induced motor deficits. Regardless of whether it was achieved with muscle (α-bugarotoxin), nerve (α-latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2-PyP5+ and/or MnTnBuOE-2-PyP5+ blocked mitochondrial ROS to significantly reduce neurotoxin and endogenous pruning cue induced motor deficits. Selectively inducing mitochondrial ROS—using mitochondria-targeted Paraquat (MitoPQ)—recapitulated synaptic inactivity induced motor deficits; which were significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP5+. We unveil mitochondrial ROS as synaptic activity sentinels that regulate the phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel results are relevant to pruning because synaptic inactivity is one of its defining features

Performance benchmarking microplate-immunoassays for quantifying target-specific cysteine oxidation reveals their potential for understanding redox-regulation and oxidative stress

The antibody-linked oxi-state assay (ALISA) for quantifying target-specific cysteine oxidation can benefit specialist and non-specialist users. Specialists can benefit from time-efficient analysis and high-throughput target and/or sample n-plex capacities. The simple and accessible “off-the-shelf” nature of ALISA brings the benefits of oxidative damage assays to non-specialists studying redox-regulation. Until performance benchmarking establishes confidence in the “unseen” microplate results, ALISA is unlikely to be widely adopted. Here, we implemented pre-set pass/fail criteria to benchmark ALISA by robustly evaluating immunoassay performance in diverse biological contexts. ELISA-mode ALISA assays were accurate, reliable, and sensitive. For example, the average inter-assay CV for detecting 20%- and 40%-oxidised PRDX2 or GAPDH standards was 4.6% (range: 3.6–7.4%). ALISA displayed target-specificity. Immunodepleting the target decreased the signal by ∼75%. Single-antibody formatted ALISA failed to quantify the matrix-facing alpha subunit of the mitochondrial ATP synthase. However, RedoxiFluor quantified the alpha subunit displaying exceptional performance in the single-antibody format. ALISA discovered that (1) monocyte-to-macrophage differentiation amplified PRDX2-specific cysteine oxidation in THP-1 cells and (2) exercise increased GAPDH-specific cysteine oxidation in human erythrocytes. The “unseen” microplate data were “seen-to-be-believed” via orthogonal visually displayed immunoassays like the dimer method. Finally, we established target (n = 3) and sample (n = 100) n-plex capacities in ∼4 h with 50–70 min hands-on time. Our work showcases the potential of ALISA to advance our understanding of redox-regulation and oxidative stress

Performance benchmarking microplate-immunoassays for quantifying target-specific cysteine oxidation reveals their potential for understanding redox-regulation and oxidative stress

The antibody-linked oxi-state assay (ALISA) for quantifying target-specific cysteine oxidation can benefit specialist and non-specialist users. Specialists can benefit from time-efficient analysis and high-throughput target and/or sample n-plex capacities. The simple and accessible “off-the-shelf” nature of ALISA brings the benefits of oxidative damage assays to non-specialists studying redox-regulation. Until performance benchmarking establishes confidence in the “unseen” microplate results, ALISA is unlikely to be widely adopted. Here, we implemented pre-set pass/fail criteria to benchmark ALISA by robustly evaluating immunoassay performance in diverse biological contexts. ELISA-mode ALISA assays were accurate, reliable, and sensitive. For example, the average inter-assay CV for detecting 20%- and 40%-oxidised PRDX2 or GAPDH standards was 4.6% (range: 3.6–7.4%). ALISA displayed target-specificity. Immunodepleting the target decreased the signal by ∼75%. Single-antibody formatted ALISA failed to quantify the matrix-facing alpha subunit of the mitochondrial ATP synthase. However, RedoxiFluor quantified the alpha subunit displaying exceptional performance in the single-antibody format. ALISA discovered that (1) monocyte-to-macrophage differentiation amplified PRDX2-specific cysteine oxidation in THP-1 cells and (2) exercise increased GAPDH-specific cysteine oxidation in human erythrocytes. The “unseen” microplate data were “seen-to-be-believed” via orthogonal visually displayed immunoassays like the dimer method. Finally, we established target (n = 3) and sample (n = 100) n-plex capacities in ∼4 h with 50–70 min hands-on time. Our work showcases the potential of ALISA to advance our understanding of redox-regulation and oxidative stress

Exercise decreases PP2A-specific reversible thiol oxidation in human erythrocytes:Implications for redox biomarkers

New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans because overtly flawed, technically fraught, and unspecific assays severely hamper translational progress. The antibody-linked oxi-state assay (ALISA) makes it possible to develop valid ROS-sensitive target-specific protein thiol redox state biomarkers in a readily accessible microplate format. Here, we used a maximal exercise bout to disrupt redox homeostasis in a physiologically meaningful way to determine whether the catalytic core of the serine/threonine protein phosphatase PP2A is a candidate systemic redox biomarker in human erythrocytes. We reasoned that: constitutive oxidative stress (e.g., haemoglobin autoxidation) would sensitise erythrocytes to disrupted ion homeostasis as manifested by increased oxidation of the ion regulatory phosphatase PP2A. Unexpectedly, an acute bout of maximal exercise lasting ˜16 min decreased PP2A-specific reversible thiol oxidation (redox ratio, rest: 0.46; exercise: 0.33) without changing PP2A content (rest: 193 pg/ml; exercise: 191 pg/ml). The need for only 3-4 μl of sample to perform ALISA means PP2A-specific reversible thiol oxidation is a capillary-fingertip blood-compatible candidate redox biomarker. Consistent with biologically meaningful redox regulation, thiol reductant-inducible PP2A activity was significantly greater (+10%) at rest compared to exercise. We establish a route to developing new readily measurable protein thiol redox biomarkers for understanding the biological roles ROS play in humans

Biosemiotics, politics and Th.A. Sebeok’s move from linguistics to semiotics

This paper will focus on the political implications for the language sciences of Sebeok’s move from linguistics to a global semiotic perspective, a move that ultimately resulted in biosemiotics. The paper will seek to make more explicit the political bearing of a biosemiotic perspective in the language sciences and the human sciences in general. In particular, it will discuss the definition of language inherent in Sebeok’s project and the fundamental re-drawing of the grounds of linguistic debate heralded by Sebeok’s embrace of the concept of modelling. Thus far, the political co-ordinates of the biosemiotic project have not really been made explicit. This paper will therefore seek to outline 1. how biosemiotics enables us to reconfigure our understanding of the role of language in culture; 2. how exaptation is central to the evolution of language and communication, rather than adaptation; 3. how communication is the key issue in biosphere, rather than language, not just because communication includes language but because the language sciences often refer to language as if it were mere “chatter”, “tropes” and “figures of speech”; 4. how biosemiotics, despite its seeming “neutrality” arising from its transdisciplinarity, is thoroughly political; 5. how the failure to see the implications of the move from linguistics to semiotics arises from the fact that biosemiotics is devoid of old style politics, which is based on representation (devoid of experience) and “construction of [everything] in discourse” (which is grounded in linguistics, not communication study). In contrast to the post-“linguistic turn” idea that the world is “constructed in discourse”, we will argue that biosemiotics entails a reconfiguration of the polis and, in particular, offers the chance to completely reconceptualise ideology

Understanding the role of the stroke physician in early supported discharge services. Collaborative Leadership in Applied Health rRsearch and Care (CLAHRC), Nottinghamshire, Derbyshire and Lincolnshire, UK

Our recent research, using expert consensus with trialists who had contributed to the Cochrane systematic review, has helped to establish key components of effective Stroke Early Supported Discharge (ESD) services. One essential element is that the ESD multidisciplinary team should have access to specialist stroke knowledge. However, how this is organised and put into working practice is less well-defined