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Rimicaris exoculatashrimps from hydrothermal vent ecosystems are known to host dense epibiotic communities inside their enlarged heads and digestive systems. Conversely, other shrimps from the family, described as opportunistic feeders have received less attention. We examined the nutrition and bacterial communities colonizing “head” chambers and digestive systems of three other alvinocaridids –Rimicaris variabilis,Nautilocaris saintlaurentaeandManuscarissp. – using a combination of electron microscopy, stable isotopes and sequencing approaches. Our observations inside “head” cavities and on mouthparts showed only a really low coverage of bacterial epibionts. In addition, no clear correlation between isotopic ratios and relative abundance of epibionts on mouthparts could be established among shrimp individuals. Altogether, these results suggest that none of these alvinocaridids rely on chemosynthetic epibionts as their main source of nutrition. Our analyses also revealed a substantial presence of several Firmicutes within the foreguts and midguts of these shrimps, which closest known lineages were systematically digestive epibionts associated with alvinocaridids, and more broadly from digestive systems of other crustaceans from marine and terrestrial ecosystems. Overall, our study opens new perspectives not only about chemosynthetic symbioses of vent shrimps, but more largely about digestive microbiomes with potential ancient and evolutionarily conserved bacterial partnerships among crustaceans.

Spectrum of $^7$Li and elastic scattering reaction $^4$He($^3$H, $^3$H)$^4$He are studied using the unified description of the Gamow shell model in the coupled-channel formulation (GSMCC). The reaction channels are constructed using the cluster expansion with the two mass partitions [$^4$He + $^3$H], [$^6$Li + n]., Comment: 10 pages, 3 figures. Presented at Zakopane 2022 Conference on Nuclear Physics

17 pages; International audience; Kelp forests dominated by Macrocystis pyrifera are widely distributed in coastal waters from boreal, temperate and subantarctic regions. This widespread distribution may result in regional differences in food web structure and functioning. In temperate northern regions, where most studies on kelp forest benthic food webs have been conducted, kelp grazing is a well-documented phenomenon and can lead to the overgrazing of M. pyrifera by sea urchins when their predators (e.g., sea otters) are absent. In contrast, little is known about their counterparts in subantarctic areas. The present study aimed to reconstruct the benthic food web of a kelp forest dominated by M. pyrifera in a subantarctic environment using stable isotope analysis. Stable carbon (δ13C), nitrogen (δ15N) and sulfur (δ34S) isotope ratios were measured from food sources (macrophytobenthos, suspended particulate organic matter SPOM, and sediment) and consumers (sponges, bivalves, gastropods, sedentary and mobile polychaetes, arthropods and echinoderms) which were sampled in a kelp forest of the Kerguelen archipelago. Mixing models highlighted two interconnected trophic pathways which were either supported by SPOM and resuspended macrophytobenthos detritus (bentho-pelagic), or by live micro/macrophytobenthos (phytobenthos-based). No major prey were highlighted for several consumers, indicating the existence of potential supplementary trophic pathways. No consumer relying primarily on living M. pyrifera was highlighted by the mixing models. The investigated kelp forest is hence a complex ecosystem supporting multiple trophic pathways, and direct consumption of M. pyrifera is limited. Nonetheless, M. pyrifera and other macrophytobenthos species may constitute a pool of detritus supporting several trophic pathways.

Alzheimer's disease (AD) is a common neurodegenerative disease that leads to memory and cognitive impairment. Exercise is suggested to prevent it. However, the exact mechanism remains unclear. This study investigated the effect of moderate exercise on cognitive function, oxidative stress and neuro-inflammation in the hippocampal tissue of experimentally-induced AD rats and the possible role of Nuclear Factor Erythroid 2- Related Factor 2 (NRF2) in mediating this effect. Forty adult male albino rats were divided into control and AD groups. Each group is further subdivided into sedentary and exercised ones. AD was induced by intraperitoneal injection with aluminium chloride (70 mg/kg b.w.) for 6 weeks. Exercise protocol was done by swimming 60 min, 5 times a week for 4 weeks. The following parameters were evaluated in all groups: hippocampal tissue assessment of NRF2, amyloid beta, malondialdehyde, interleukin 6 and total antioxidant capacity. Assessment of cognitive performance was done using Morris water maze at weeks 3, 4 and 6 after AD induction. Results revealed significantly lower hippocampal NRF2 and TAC levels with significant higher Aβ, MDA, IL-6 and impaired cognitive dysfunction in sedentary AD rats. These were reversed by swimming exercise. NRF2 was negatively correlated with Aβ, IL-6 and MDA in both AD groups with positive correlation with TAC. In conclusion, moderate swimming exercise exerts neuroprotective effects in AD through improvement of cognitive function, restoration of the antioxidant and anti-inflammatory capacity. The upregulation of NRF2 could mediate these effects. Therefore, targeting NRF2 could be promising as a therapeutic agent for neurodegenerative diseases.

Funding Acknowledgements Type of funding sources: None. Background Despite the increasing number of studies concerning Left Atrial Strain (LAS), few data are available comparing LAS patients with cardiac amyloidosis (CA) and sarcomeric hypertrophic cardiomyopathies (HCM). Purposes We aimed to perform a comparative multimodal imaging analysis of LAS of a prospective cohort of patients with CA and HCM. Methods For each enrolled patient, we performed same-day two and three-dimension echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) to blindly measure the peak atrial longitudinal strain (PALS) and the peak atrial contraction strain (PACS). Patients with acute atrial fibrillation were excluded. Results Between January 2020 and July 2021, 67 patients were included: 31 patients with CA (age 75.1 ± 10 years, left ventricular ejection fraction 60.6 ± 10.4%, maximum left ventricular thickness 17.8 ± 3.9 mm) and 36 with HCM (age 50.8 ± 15.5 years, left ventricular ejection fraction 66.1 ± 9.8%, maximum left ventricular thickness 20.7 ± 4.5 mm). Left atrial volume was similar in the 2 groups (42.5 ± 15.6 mL/m2 in HCM vs 47.9 ± 15 in CA, P = 0.1557). Concerning PALS, its values for CA and for CMH were on 2D TTE manual (10.9 ± 5.8% vs 21.4 ± 9.4%, P Concerning PACS, its values for CA and for CMH were on 2D TTE manual (5.2 ± 3.4% vs 10 ± 4%, P Multivariate analysis adjusted on main factors influencing LAS (left ventricular (LV) mass, LV ejection fraction, LV global longitudinal strain, renal function and history of hypertension) found that the differences between the two groups remained significant for PALS and PACS for almost all technics. Furthermore, although concordance between the 3 echocardiographic technics was excellent (the interclass correlation coefficient (ICC) was higher than 0.80 between each TTE methods), ICC was poor between TTE and CMR technics: 0.40 (0.18-0.59) for manual 2D TTE and CMR, 0.46 (0.24-0.63) for auto 2D TTE and CMR, 0.40 (0.14-0.60) for 3D TTE and CMR. Conclusion Our study is the first to describe and compare, both on TTE and CMR, LAS on a prospective cohort of patients with CA and HCM. Although they have same mean left atrial volume, we found significant differences on PALS and PACS between these two groups of patients on all the studied technics. These findings may be used in future multi-modality imaging studies dealing with diagnosis or prognosis of these hypertrophic cardiopathies. Abstract Figure. LAS 2D TTE manual Abstract Figure. LAS comparison between CA and HCM

Although they are part of the lightest nuclei, the hydrogen isotopes are not well understood both experimentally and theoretically. Indeed, besides deuteron and triton, all known hydrogen isotopes are resonances of complex structure. Even more elusive is 7H, which may have been observed experimentally and has been claimed to be a narrow resonance. Nevertheless, even its existence is controversial, and its theoretical study is difficult due to both its unbound character and large number of interacting valence nucleons. It is then the object of this paper to theoretically study the hydrogen isotopes {4-7}H with the Gamow shell model, which is, up to our knowledge, the first direct calculation of unbound resonance hydrogen isotopes up to 7H. As the Gamow shell model includes both continuum coupling and inter-nucleon correlations, useful information can be obtained about poorly known unbound hydrogen isotopes. Our present calculations indicate that {4,6}H ground states are fairly broad resonances, whereas those of {5,7}H are narrow, which is in accordance with current experimental data. The results then suggest that, in particular, {5,7}H should be more heavily studied, as they might well be among the most narrow neutron resonances of the light nuclear chart.

Sea stars (Echinodermata: Asteroidea) are a key component of Southern Ocean benthos, with 16% of the known sea star species living there. In temperate marine environments, sea stars commonly play an important role in food webs, acting as keystone species. However, trophic ecology and functional role of Southern Ocean sea stars are still poorly known, notably due to the scarcity of large-scale studies. Here, we report 24332 trophic marker (stable isotopes and elemental contents of C, N and S of tegument and/or tube feet) and biometric (arm length, disk radius, arm to disk ratio) measurements in 2456 specimens of sea stars. Samples were collected between 12/01/1985 and 08/10/2017 in numerous locations along the Antarctic littoral and Subantarctic islands. The spatial scope of the dataset covers a significant portion of the Southern Ocean (Latitude: 47.717° South to 86.273° South; longitude: 127.767° West to 162.201° East; depth: 6 to 5338 m). The dataset contains 133 distinct taxa, including 72 currently accepted species spanning 51 genera, 20 families and multiple feeding guilds / functional groups (suspension feeders, sediment feeders, omnivores, predators of mobile or sessile prey). For 505 specimens, mitochondrial CO1 genes were sequenced to confirm and/or refine taxonomic identifications, and those sequences are already publicly available through the Barcode of Life Data System. This number will grow in the future, as molecular analyses are still in progress. Overall, thanks to its large taxonomic, spatial, and temporal extent, as well as its integrative nature (combining genetic, morphological and ecological data), this dataset can be of wide interest to Southern Ocean ecologists, invertebrate zoologists, benthic ecologists, and environmental managers dealing with associated areas. Please cite this data paper in research products derived from the dataset, which is freely available without copyright restrictions.

Single-nucleon knockout reaction studies of the proton-dripline nuclei $^9$C and $^{13}$O suggest an appreciable suppression of spectroscopic factors. In this work, we calculate the one-neutron and one-proton spectroscopic factors for the mirror pair $^9$C-$^9$Li and $^{13}$O using two variants of the continuum shell model: the complex-energy Gamow Shell Model and the real-energy Shell Model Embedded in the Continuum. Our results indicate that the continuum effects strongly suppress the spectroscopic factors of well-bound orbits in the dripline systems, but have less impact on the spectroscopic factors of weakly-bound states., 7 pages, 3 figures, 1 table

A kinematically complete quasi-free $(p,pn)$ experiment in inverse kinematics was performed to study the structure of the Borromean nucleus $^{17}$B, which had long been considered to have neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for $1s_{1/2}$ and $0d_{5/2}$ orbitals, and a surprisingly small percentage of 9(2)$\%$ was determined for $1s_{1/2}$. Our finding of such a small $1s_{1/2}$ component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in $^{17}$B. The present work gives the smallest $s$- or $p$-orbital component among known nuclei exhibiting halo features, and implies that the dominant occupation of $s$ or $p$ orbitals is not a prerequisite for the occurrence of neutron halo., Accepted for publication in Physical Review Letters,8 pages, 4 figures

The model of Paricaud (2011) has previously been shown to be able to accurately correlate the three-phase equilibrium conditions of TBAB semi-clathrates in the presence of pure CO2. While the model of Paricaud (2011) was derived in a manner that was expected to make it relatively straight forward correlating the three-phase equilibrium conditions of semi-clathrates in the presence of mixed gases this capability has not, at the time of writing, been tested. In the present work, the model of Paricaud (2011), along with the modification of Garcia et al. (2016), is examined for its ability to correlate the three-phase equilibrium conditions of TBAB semi-clathrates formed in the presence of binary mixtures of (CO2 + N2), (CO2 + H2), (CO2 + CH4), and (CO2 + CO) and in the presence of a ternary mixture of (CO2 + H2+CO). The computations were carried out at temperatures between (281 and 293) K, at pressures between (2.0 and 6.6) MPa and in aqueous TBAB solutions of wTBAB = (0.05, 0.10, and 0.20). The average absolute relative deviation of the correlations ranged from 3.7%, for TBAB semi-clathrates formed in the presence of an equimolar mixture of (CO2 + N2), to 7.1%, for TBAB semi-clathrates formed in the presence of a ternary gas mixture of (CO2 + H2+CO).

Introduction La Polyarthrite Rhumatoïde (PR) est le plus fréquent des rhumatismes inflammatoires chroniques. Le facteur rhumatoïde (FR) est très fréquemment positif dans la PR (70 à 80 %), sans être spécifique de cette pathologie puisqu’il s’observe dans d’autres pathologies auto-immunes, infectieuses ou hématologiques (Ingegnoli - 2013). Il est probable que les différents éléments à l’origine de faux positifs lors des tests sérologiques visant SARS-CoV, en particulier la présence d’auto-anticorps dont le FR, soit aussi à l’origine de faux positifs lors de la réalisation de tests sérologiques visant le SARS-CoV-2. Ce projet a pour but de valider et d’optimiser les tests diagnostiques sérologiques COVID-19 pour pouvoir mieux interpréter les faux positifs dans cette population particulière de patients avec FR positif, afin de choisir le test idéal pour minimiser les faux positifs. Matériels et méthodes Étude rétrospective. 265 sérums des échantillons des patients atteints de PR prélevé avant 07/2019 pour assurer la vraie négativité au Covid-19 ont été inclus et répartis en 2 groupes Groupe 1(G1) : PR séropositive pour le FR+ et Groupe 2 (G2) : PR séronégative pour le FR- Une analyse de FR et de ses sous-types de FR (IgM et IgA) a été réalisé pour évaluer l’influence sur la spécificité des 3 différents tests sérologiques du SARS-CoV-2(UNscience, SureScreen, iSIA) disponibles pour la détection des IgG et IgM spécifiques et l’analyse ELISA de SARS-CoV-2. Résultats G1 : n = 210 ; G2 : n = 55. Résultats : G1 : UNscience : spécificité : 91 % (taux de faux positifs : 9,0 %) ; SureScreen : spécificité : 92 % (taux de faux positifs : 7,6 %) ; iSIA : spécificité : 58 % (taux de faux positifs : 44,3 %) ; ELISA : spécificité : 99 % (taux de faux positifs : 1,0 %) G2 : UNscience : spécificité : 98 % (taux de faux positifs : 1,8 %) ; SureScreen : spécificité : 96 % (taux de faux positifs : 3,6 %) ; iSIA : spécificité : 91 % (taux de faux positifs : 9,1 %) ; ELISA : spécificité : 98 % (taux de faux positifs : 1,8 %). Les sous-types de FR associé à la fausse positivité du test : Unscience IgA ; iSIA IgA et IgM ; SureScreen. Discussion Si on compare les patients PR en fonction de la positivité du FR et selon la positivité des IgM et/ou des IgA, le taux de faux positifs SARS-CoV-2 est significativement supérieur dans le groupe FR positif si les IgA et les IgM sont positives. Les analyses stratifiées confrontant respectivement les taux d’IgM et d’IgA ont montré que la proportion des faux positifs avec le test iSIA augmentait avec les taux d’IgA et d’IgM. La spécificité du test iSIA est fortement influencée par la présence du FR, raison pour laquelle ce test ne devrait pas être un choix de test sérodiagnostic du SARS-CoV-2 pour cette poblation. Conclusion Si on compare chacun de 3 test sérodiagnostic du SARS-CoV-2 rapides et le test Elisa chez des patients porteurs de FR on observe un taux de faux positifs significativement supérieur avec le test iSIA comme en témoigne un taux de faux positifs significativement plus élevé avec le FR positif (44,3 %) que parmi les sérums FR négatif (9,5 %). Pour pouvoir mieux interpréter un résultat de sérologie SARS-Cov2, il faut tenir compte de la positivité du FR. Le test ELISA parait le plus approprié.

Myotonic Dystrophy type 1 (DM1) is caused by an expansion of CUG repeats in DMPK mRNAs. This mutation affects alternative splicing through misregulation of RNA-binding proteins. Amongst pre-mRNAs that are mis-spliced, several code for proteins involved in calcium homeostasis suggesting that calcium-handling and signaling are perturbed in DM1. Here, we analyzed expression of such proteins in DM1 mouse muscle. We found that the levels of several sarcoplasmic reticulum proteins (SERCA1, sarcolipin and calsequestrin) are altered, likely contributing to an imbalance in calcium homeostasis. We also observed that calcineurin (CnA) signaling is hyperactivated in DM1 muscle. Indeed, CnA expression and phosphatase activity are both markedly increased in DM1 muscle. Coherent with this, we found that activators of the CnA pathway (MLP, FHL1) are also elevated. Consequently, NFATc1 expression is increased in DM1 muscle and becomes relocalized to myonuclei, together with an up-regulation of its transcriptional targets (RCAN1.4 and myoglobin). Accordingly, DM1 mouse muscles display an increase in oxidative metabolism and fiber hypertrophy. To determine the functional consequences of this CnA hyperactivation, we administered cyclosporine A, an inhibitor of CnA, to DM1 mice. Muscles of treated DM1 mice showed an increase in CUGBP1 levels, and an exacerbation of key alternative splicing events associated with DM1. Finally, inhibition of CnA in cultured human DM1 myoblasts also resulted in a splicing exacerbation of the insulin receptor. Together, these findings show for the first time that calcium-CnA signaling is hyperactivated in DM1 muscle and that such hyperactivation represents a beneficial compensatory adaptation to the disease.

International audience; This paper reports on atomic layer etching of several III-N materials such as GaN, AlN, AlGaN, and InAlGaN based on a sequential surface modification by chlorine adsorption followed by a low energy Ar plasma exposure to remove the modified layer using a reactive ion etching system. A study on the influence of several parameters, such as gas flow rates, removal step duration, RIE power and number of cycles on the etch per cycle, and the root-mean-square roughness, is performed. Low etch per cycle from 0.17 to 1.85 nm/cycle, respectively, for AlGaN and GaN and surfaces as smooth as the as-grown samples were obtained. The developed process is intended to be used for normally off GaN-based high electron mobility transistor processing.

Purpose: Deformation analysis from 3D echocardiography results in a considerable amount of parameters, for which the conventional statistical approach is cumbersome. We investigate local motion and deformation patterns to determine the parameters of relevance for the study of LV myocardial deformation in the presence of LAD infarct. Methods: The study included 46 patients acquired at max. 5 days after LAD infarct (37 sequences) and at 1-year follow-up (33 sequences), and 46 controls. Patients were selected if they had a LVEF

The Mediterranean Sea remains a complex system for mercury (Hg) cycling and accumulation in marine vertebrates. The extremely high levels these animals present demand for an urgent understanding of such processes and the development of new analytical techniques that go beyond the simple contamination monitoring. It was often proposed that prey selection or habitat use may affect Hg contamination in animals; however, it was never possible to measure which factor influences more rates and pathways of contamination. In this paper, we directly integrate toxicological information (Hg levels) and ecological tracers (stable isotopes of C, N and S) into a common data analysis framework (isotopic niches), with the aim of quantifying the influence of species’ trophic behaviour on Hg contamination. The analysis was conducted on skin biopsies of fin whales Balaenoptera physalus, long-finned pilot whales Globicephala melas and sperm whales Physeter microcephalus. Their different trophic modes and residency in the area make them model species for the analysis of Hg accumulation along NWMS food webs. We measured Total Hg (T-Hg) concentrations through absorbance spectrometry with the DMA80 Milestone. Carbon, nitrogen and sulphur isotope compositions were measured via mass spectrometry in an IRMS coupled to an Elemental Analyser (EA) Isoprime. Comparison of ecological and contamination niches allowed to explain Hg accumulation in Mediterranean marine predators. Factors such as food web complexity, trophic position, hunting distribution or habitat use (e.g., foraging depth) did not influence Hg exposure. It is rather the selection of prey type, which determines the range of potential Hg sources and as a consequence the rates of accumulation in whales’ tissues. A generalist piscivorous species such as the pilot whales will bioaccumulate more Hg than specialised sperm whales feeding mostly on cephalopods.

Centronuclear myopathy (CNM) is a congenital myopathy that is histopathologically characterized by centrally located nuclei, central aggregation of oxidative activity, and type I fiber predominance and hypotrophy. Here, we obtained commercially available mice overexpressing phospholamban (PlnOE), a well-known inhibitor of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), in their slow-twitch type I skeletal muscle fibers to determine the effects on SERCA function. As expected with a 6- to 7-fold overexpression of phospholamban, SERCA dysfunction was evident in PlnOE muscles, with marked reductions in rates of Ca2+ uptake, maximal ATPase activity and the apparent affinity of SERCA for Ca2+. However, our most significant discovery was that the soleus and gluteus minimus muscles from the PlnOE mice displayed overt signs of myopathy: they histopathologically resembled human CNM, with centrally located nuclei, central aggregation of oxidative activity, type I fiber predominance and hypotrophy, progressive fibrosis and muscle weakness. This phenotype is associated with significant upregulation of muscle sarcolipin and dynamin 2, increased Ca2+-activated proteolysis, oxidative stress and protein nitrosylation. Moreover, in our assessment of muscle biopsies from three human CNM patients, we found a significant 53% reduction in SERCA activity and increases in both total and monomeric PLN content compared with five healthy subjects, thereby justifying future studies with more CNM patients. Altogether, our results suggest that the commercially available PlnOE mouse phenotypically resembles human CNM and could be used as a model to test potential mechanisms and therapeutic strategies. To date, there is no cure for CNM and our results suggest that targeting SERCA function, which has already been shown to be an effective therapeutic target for murine muscular dystrophy and human cardiomyopathy, might represent a novel therapeutic strategy to combat CNM., Summary: Phospholamban overexpression in mouse slow-twitch muscle impairs SERCA function and causes histopathological features associated with human centronuclear myopathy.

The calcineurin–NFAT (nuclear factor of activated T-cells) signalling pathway is involved in the regulation of activity-dependent skeletal muscle myosin heavy chain (MHC) isoform type expression. Emerging evidence indicates that nitric oxide (NO) may play a critical role in this regulatory pathway. Thus, the purpose of this study was to investigate the role of NO in activity-induced calcineurin–NFATc1 signalling leading to skeletal muscle faster-to-slower fibre type transformations in vivo. Endogenous NO production was blocked by administering L-NAME (0.75 mg ml(−1)) in drinking water throughout 0, 1, 2, 5 or 10 days of chronic low-frequency stimulation (CLFS; 10 Hz, 12 h day(−1)) of rat fast-twitch muscles (L+Stim; n = 30) and outcomes were compared with control rats receiving only CLFS (Stim; n = 30). Western blot and immunofluorescence analyses revealed that CLFS induced an increase in NFATc1 dephosphorylation and nuclear localisation, sustained by glycogen synthase kinase (GSK)-3β phosphorylation in Stim, which were all abolished in L+Stim. Moreover, real-time RT-PCR revealed that CLFS induced an increased expression of MHC-I, -IIa and -IId(x) mRNAs in Stim that was abolished in L+Stim. SDS-PAGE and immunohistochemical analyses revealed that CLFS induced faster-to-slower MHC protein and fibre type transformations, respectively, within the fast fibre population of both Stim and L+Stim groups. The final fast type IIA to slow type I transformation, however, was prevented in L+Stim. It is concluded that NO regulates activity-induced MHC-based faster-to-slower fibre type transformations at the transcriptional level via inhibitory GSK-3β-induced facilitation of calcineurin–NFATc1 nuclear accumulation in vivo, whereas transformations within the fast fibre population may also involve translational control mechanisms independent of NO signalling.

In this paper we present a stability theory for discontinuous dynamical systems (DDS): continuous-time systems whose motions are not necessarily continuous with respect to time. We show that this t...

In this study, we crossbred mdx mice with transgenic mice expressing a small peptide inhibitor for calmodulin (CaM), known as the CaM-binding protein (CaMBP), driven by the slow fiber-specific troponin I slow promoter. This strategy allowed us to determine the impact of interfering with Ca(2+)/CaM-based signaling in dystrophin-deficient slow myofibers. Consistent with impairments in the Ca(2+)/CaM-regulated enzymes calcineurin and Ca(2+)/CaM-dependent kinase, the nuclear accumulation of nuclear factor of activated T-cell c1 and myocyte enhancer factor 2C was reduced in slow fibers from mdx/CaMBP mice. We also detected significant reductions in the levels of peroxisome proliferator gamma co-activator 1alpha and GA-binding protein alpha mRNAs in slow fiber-rich soleus muscles of mdx/CaMBP mice. In parallel, we observed significantly lower expression of myosin heavy chain I mRNA in mdx/CaMBP soleus muscles. This correlated with fiber-type shifts towards a faster phenotype. Examination of mdx/CaMBP slow muscle fibers revealed significant reductions in A-utrophin, a therapeutically relevant protein that can compensate for the lack of dystrophin in skeletal muscle. In accordance with lower levels of A-utrophin, we noted a clear exacerbation of the dystrophic phenotype in mdx/CaMBP slow fibers as exemplified by several pathological indices. These results firmly establish Ca(2+)/CaM-based signaling as key to regulating expression of A-utrophin in muscle. Furthermore, this study illustrates the therapeutic potential of using targets of Ca(2+)/CaM-based signaling as a strategy for treating Duchenne muscular dystrophy (DMD). Finally, our results further support the concept that strategies aimed at promoting the slow oxidative myofiber program in muscle may be effective in altering the relentless progression of DMD.

Heat shock protein 72 (Hsp70) is constitutively expressed in rat hindlimb muscles, reportedly in proportion to their content of type I myosin heavy chain. This distribution pattern has been suggested to result from the higher recruitment and activity of such muscles and/or a specific relationship between myosin phenotype and Hsp70 content. To differentiate between these possibilities, the fiber-specific distribution of Hsp70 was examined in male Sprague-Dawley rat plantaris under control conditions, following a fast-to-slow phenotypic shift in response to surgically induced overload (O) and in response to O when the phenotypic shift was prevented by 3,5,3′-triiodo-dl-thyronine administration. Constitutive expression of Hsp70 was restricted to type I and IIa fibers in plantaris from control rats, and this fiber-specific pattern of expression was maintained following O of up to 28 days, although Hsp70 content in the O muscle doubled. When O (for 40 days) of the plantaris was combined with 3,5,3′-triiodo-dl-thyronine administration, despite typical hypertrophy in the overloaded plantaris, prevention of the normal phenotypic transformation also blocked the increased expression of Hsp70 observed in euthyroid controls. Collectively, these data suggest that chronic changes in constitutive expression of Hsp70 with altered contractile activity appear critically dependent on fast-to-slow phenotypic remodeling.

We present Lyapunov stability results for discontinuous dynamical systems (DDS) determined by linear and nonlinear semigroups defined on Banach space. DDS of the type considered herein arise in the modeling of a variety of finite- and infinite-dimensional systems, including certain classes of hybrid systems, discrete-event systems, switched systems, systems subjected to impulse effects, and the like. We apply our results in the analysis of several important specific classes of DDS.

We present Lyapunov stability results, including converse theorems, for a class of discontinuous dynamical systems (DDS) determined by the solutions of retarded functional differential equations. We demonstrate the applicability of these results in the analysis of several specific important classes of DDS determined by functional differential equations and differential-difference equations.

Recruitment determines the profile of fibre-type-specific genes expressed across the range of muscle fibres associated with slow, fast fatigue-resistant and fast fatiguable motor units. Downstream signalling pathways activated by neural signalling and mechanical load have been the focus of intensive research in past years. It is now known that Ca2+-dependent calcineurin–nuclear factor of activated T cells and insulin-like growth factor 1 pathways and their downstream mediators contribute to these adaptive responses. These pathways regulate gene expression through muscle-specific (myocyte-enhancing factor 2, myoblast determination protein) and non-specific (nuclear factor of activated T cell 2, GATA-2) transcription factors. Transcriptional signals activated with increased contractile activity result in altered expression of fibre-type specific genes, including the myosin heavy chain isoforms and oxidative and glycolytic enzymes and a net change in muscle fibre-type composition. In contrast, transcriptional signals activated by increased load bearing result in hypertrophy or a growth response, a component of which involves satellite cell recruitment and fusion with existing adult myofibres. Calcineurin has been identified as a key mediator in the hypertrophic response, and the current challenge has been to determine the downstream target genes of this pathway. Exciting new data have emerged, showing that myostatin, a negative regulator of muscle growth, and utrophin, a cytoskeletal protein important in maintaining membrane integrity, are downstream targets of calcineurin signalling. Increased understanding of these mediators of muscle growth may provide strategies for the development of effective therapeutics to counter muscle weakness and muscular dystrophy.

The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58 % type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 +/- 2.6 vs. 55.1 +/- 4.7 ms; half-relaxation time: 42.1 +/- 3.5 vs. 68.1 +/- 9.6 ms, P0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 +/- 0.4 % in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64 % reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.

The ZrNi–H2 phase diagram indicates the presence of two stable hydrides: a triclinic monohydride ZrNiH and an orthorhombic trihydride ZrNiH3 [1] . In this paper, we present the results of some thermodynamic, microstructural and electronic properties of the ZrNi–H2 system. A strict control of the thermodynamic variables (P, T) during the hydride phase growth allowed us to prepare two samples of overall composition ZrNiH0.70 and ZrNiH2.5. In a first step, the microstructure evolutions induced by hydrogen absorption are investigated during the activation process. The intermetallic and hydrided compounds are studied by energy dispersive X-ray spectroscopy (EDXS) and X-ray diffraction (XRD) methods. The nature of defects generated in ZrNi and its hydrides compounds are observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Ab-initio electronic structure calculations have been performed. They clearly show the importance of chemical effects besides geometrical factors in explaining the preferential site occupancy of hydrogen atoms in the ZrNiH phase.

First principles electronic structure calculations are reported for hydrogen absorbing intermetallic compounds belonging to an important class of Laves phases: the superconducting AB 2 compounds (with A=Zr, Hf; B=V). The C-15 Laves phases Zr x Hf 1− x V 2 have a maximum superconducting critical temperature of T c max =10 K for x =0.5. The large value of the electron–phonon coupling constant of these intermetallic compounds is mainly associated with the existence of high peaks in the density of states (DOS) at the Fermi energy, E F . In contrast, the hydrogen-rich phases are not superconducting. We analyze the modifications in the electronic states at E F due to the formation of hydrides and discuss the observed changes in the superconducting properties, the magnetic susceptibility and the electronic specific heat coefficient. The metal–hydrogen interactions are analyzed in terms of partial wave decomposition of the DOS. These results are used to interpret the available photoemission and X-ray emission spectra.

In this paper, we investigate some qualitative properties for time-controlled switched systems consisting of several linear discrete-time subsystems. First, we study exponential stability of the switched system with commutation property, stable combination and average dwell time. When all subsystem matrices are commutative pairwise and there exists a stable combination of unstable subsystem matrices, we propose a class of stabilizing switching laws where Schur stable subsystems (if exist) are activated arbitrarily while unstable ones are activated in sequence with their duration time periods satisfying a specified ratio. For more general switched system whose subsystem matrices are not commutative pairwise, we show that the switched system is exponentially stable if the average dwell time is chosen sufficiently large and the total activation time ratio between Schur stable and unstable subsystems is not smaller than a specified constant. Secondly, we use an average dwell time approach incorporated with a piecewise Lyapunov function to study the L2 gain of the switched system. We show that when all subsystems are Schur stable and achieve an L2 gain smaller than a positive scalar γ0, (1) if all subsystems have a common Lyapunov function in the sense of L2 gain, then the switched system achieves the same L2 gain γ0 under arbitrary switching; (2) if there does not exist a common Lyapunov function, then the switched system under an average dwell time scheme achieves a weighted γ0 gain 70, and the weighted L2 gain approaches normal L2 gain if the average dwell time is chosen sufficiently large.

This study tested the hypothesis that calcineurin signaling is modulated in skeletal muscle cells by fluctuations in nerve-mediated activity. We show that dephosphorylation of NFATc1, MEF2A, and MEF2D transcription factors by calcineurin in all muscle types is dependent on nerve activity and positively correlated with muscle usage under normal weightbearing conditions. With increased nerve-mediated activity, calcineurin dephosphorylation of these targets was found to be potentiated in a way that paralleled the higher muscle activation profiles associated with functional overload or nerve electrical stimulation conditions. We also establish that muscle activity must be sustained above native levels for calcineurin-dependent dephosphorylation of MEF2A and MEF2D to be transduced into an increase in MEF2 transcriptional function, suggesting that calcineurin cooperates with other activity-linked events to signal via these proteins. Finally, examination of individual fiber responses to overload and nerve electrical stimulation revealed that calcineurin-MEF2 signaling occurs in all fiber types but most readily in fibers that are normally least active (i.e. those expressing IIx and IIb myosin heavy chain (MHC)), suggesting that signaling via this phosphatase is also dependent upon the activation history of the muscle cell.

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, specifically calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber-specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained.

In this paper, we establish several stability results for discontinuous dynamical systems defined onR+=[0, ∞) which make use of vector Lyapunov functions. For the scalar case, these results yield in particular theprincipal Lyapunov stability results for discontinuous dynamical systems reported earlier. We demonstrate the applicability of our results by studying a class of interconnected discontinuous dynamical systems and several specific examples.