EFFECT OF FATIGUE ON MUSCLE COORDINATION IN REPEATED ALL-OUT BOUTS

The aim of the present study was to analyse the fatigue occurring during repeated all-out short cycling bouts through mechanical and electromyographic (EMG) data and to focus on . inter-muscle coordination. The results showed a significant decrease in peak power output without significant modifications in the EMG activity through sprint repetitions. However, the coordination timing between agonist and antagonist muscles was reduced. In conclusion, power output decreased during high-intensity repeated sprints due to the inability of quadriceps to maintain maximal force and owing to inter-muscle coordination limitations

Global Optimization-Based Calibration Algorithm for a 2D Distributed Hydrologic-Hydrodynamic and Water Quality Model

Hydrodynamic models with rain-on-the-grid capabilities are usually computationally expensive. This makes the use of automatic calibration algorithms hard to apply due to the large number of model runs. However, with the recent advances in parallel processing, computational resources, and increasing high-resolution climatologic and GIS data, high-resolution hydrodynamic models can be used for optimization-based calibration. This paper presents a global optimization-based algorithm to calibrate a fully distributed hydrologic-hydrodynamic and water quality model (HydroPol2D) using observed data (i.e., discharge, or pollutant concentration) as input. The algorithm can find a near-optimal set of parameters to explain observed gauged data. The modeling framework presented here, although applied in a poorly-gauged catchment, can be adapted for catchments with more detailed observations. We applied the algorithm in different cases of the V-Tilted Catchment, the Wooden-Board catchment, and in an existing urban catchment with heterogeneous data. The results of automatic calibration indicate $\mathrm{NSE} = 0.99$ for the V-Tilted catchment, $\mathrm{RMSE} = 830~\mathrm{mgL^{-1}}$ for salt concentration pollutographs (i.e., 8.3% of the event mean concentration), and $\mathrm{NSE} = 0.89$ for the urban catchment case study. This paper also explores the issue of equifinality in modeling calibration (EqMC). Equifinality is defined as the set of different parameter combinations that can provide equally good or accepted results, within the physical parameter ranges. EqMC decreases with the number of events and increases with the choice of partially or nonproducing runoff ones. Furthermore, results indicate that providing more accurate parameter ranges based on a priori knowledge of the catchment is fundamental to reduce the chances of finding a set of parameters with equifinality.Comment: Preprint submitted to Journal of Hydrolog

Protease activated receptors 1 and 4 sensitize TRPV1 in nociceptive neurones.

Protease-activated receptors (PAR1-4) are activated by proteases released by cell damage or blood clotting, and are known to be involved in promoting pain and hyperalgesia. Previous studies have shown that PAR2 receptors enhance activation of TRPV1 but the role of other PARs is less clear. In this paper we investigate the expression and function of the PAR1, 3 and 4 thrombin-activated receptors in sensory neurones. Immunocytochemistry and in situ hybridization show that PAR1 and PAR4 are expressed in 10 - 15% of neurons, distributed across all size classes. Thrombin or a specific PAR1 or PAR4 activating peptide (PAR1/4-AP) caused functional effects characteristic of activation of the PLCβ/PKC pathway: intracellular calcium release, sensitisation of TRPV1, and translocation of the epsilon isoform of PKC (PKCε) to the neuronal cell membrane. Sensitisation of TRPV1 was significantly reduced by PKC inhibitors. Neurons responding to thrombin or PAR1-AP were either small nociceptive neurones of the peptidergic subclass, or larger neurones which expressed markers for myelinated fibres. Sequential application of PAR1-AP and PAR4-AP showed that PAR4 is expressed in a subset of the PAR1-expressing neurons. Calcium responses to PAR2-AP were by contrast seen in a distinct population of small IB4+ nociceptive neurones. PAR3 appears to be non-functional in sensory neurones. In a skin-nerve preparation the release of the neuropeptide CGRP by heat was potentiated by PAR1-AP. Culture with nerve growth factor (NGF) increased the proportion of thrombin-responsive neurons in the IB4- population, while glial-derived neurotropic factor (GDNF) and neurturin upregulated the proportion of thrombin-responsive neurons in the IB4+ population. We conclude that PAR1 and PAR4 are functionally expressed in large myelinated fibre neurons, and are also expressed in small nociceptors of the peptidergic subclass, where they are able to potentiate TRPV1 activity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons

Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors has been obtained in mouse models in vivo, but conversion using human cells has not yet been demonstrated. Such studies have been difficult to perform since hGPCs are born late during human fetal development, with limited accessibility for in vitro culture. In this study, we show proof of concept of hGPC conversion using fetal cells and also establish a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro. Using this system, we have identified optimal combinations of fate determinants for the efficient dopaminergic (DA) conversion of hGPCs, thereby yielding a therapeutically relevant cell type that selectively degenerates in Parkinson's disease. The induced DA neurons show a progressive, subtype-specific phenotypic maturation and acquire functional electrophysiological properties indicative of DA phenotype

Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination

BACKGROUND: HIV-1 recombination between different subtypes has a major impact on the global epidemic. The generation of these intersubtype recombinants follows a defined set of events starting with dual infection of a host cell, heterodiploid virus production, strand transfers during reverse transcription, and then selection. In this study, recombination frequencies were measured in the C1-C4 regions of the envelope gene in the presence (using a multiple cycle infection system) and absence (in vitro reverse transcription and single cycle infection systems) of selection for replication-competent virus. Ugandan subtypes A and D HIV-1 env sequences (115-A, 120-A, 89-D, 122-D, 126-D) were employed in all three assay systems. These subtypes co-circulate in East Africa and frequently recombine in this human population. RESULTS: Increased sequence identity between viruses or RNA templates resulted in increased recombination frequencies, with the exception of the 115-A virus or RNA template. Analyses of the recombination breakpoints and mechanistic studies revealed that the presence of a recombination hotspot in the C3/V4 env region, unique to 115-A as donor RNA, could account for the higher recombination frequencies with the 115-A virus/template. Single-cycle infections supported proportionally less recombination than the in vitro reverse transcription assay but both systems still had significantly higher recombination frequencies than observed in the multiple-cycle virus replication system. In the multiple cycle assay, increased replicative fitness of one HIV-1 over the other in a dual infection dramatically decreased recombination frequencies. CONCLUSION: Sequence variation at specific sites between HIV-1 isolates can introduce unique recombination hotspots, which increase recombination frequencies and skew the general observation that decreased HIV-1 sequence identity reduces recombination rates. These findings also suggest that the majority of intra- or intersubtype A/D HIV-1 recombinants, generated with each round of infection, are not replication-competent and do not survive in the multiple-cycle system. Ability of one HIV-1 isolate to outgrow the other leads to reduced co-infections, heterozygous virus production, and recombination frequencies

Prevalence of and risk factors for fatty liver in the general population of Northern Italy: The Bagnacavallo Study

Background: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population. Methods: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l. Results: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD. Conclusions: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes

The Variscan subduction inheritance in the Southern Alps Sub-Continental Lithospheric Mantle: clues from the Middle Triassic shoshonitic magmatism of the Dolomites (NE Italy)

Although often speculated, the link between the Middle Triassic shoshonitic magmatism at the NE margin of the Adria plate and the subduction-related metasomatism of the Southern Alps Sub-Continental Lithospheric Mantle (SCLM) has never been constrained. In this paper, a detailed geochemical and petrological characterization of the lavas, dykes and ultramafic cumulates belonging to the shoshonitic magmatic event that shaped the Dolomites (Southern Alps) was used to model the composition and evolution of the underlying SCLM in the time comprised between the Variscan subduction and the opening of the Alpine Tethys. Geochemical models and numerical simulations enabled us to define that 5–7% partial melting of an amphibole + phlogopite-bearing spinel lherzolite, similar to the Finero phlogopite peridotite, can account for the composition of the primitive Mid-Triassic SiO2-saturated to -undersaturated melts with shoshonitic affinity (87Sr/86Sri = 0.7032–0.7058; 143Nd/144Ndi = 0.51219–0.51235; Mg # ~ 70; ~1.1 wt% H2O). By taking into account the H2O content documented in mineral phases from the Finero phlogopite peridotite, it is suggested that the Mid-Triassic SCLM source was able to preserve a significant enrichment and volatile content (600–800 ppm H2O) for more than 50 Ma, i.e. since the slab-related metasomatism connected to the Variscan subduction. The partial melting of a Finero-like SCLM represents the exhaustion of the subduction-related signature in the Southern Alps lithosphere that predated the Late Triassic-Early Jurassic asthenospheric upwelling related to the opening of the Alpine Tethys