Store-operated calcium entry contributes to abnormal Ca²⁺ signalling in dystrophic mdx mouse myoblasts

Sarcolemma damage and activation of various calcium channels are implicated in altered Ca2+ homeostasis in muscle fibres of both Duchenne muscular dystrophy (DMD) sufferers and in the mdx mouse model of DMD. Previously we have demonstrated that also in mdx myoblasts extracellular nucleotides trigger elevated cytoplasmic Ca2+ concentrations due to alterations of both ionotropic and metabotropic purinergic receptors. Here we extend these findings to show that the mdx mutation is associated with enhanced store-operated calcium entry (SOCE). Substantially increased rate of SOCE in mdx myoblasts in comparison to that in control cells correlated with significantly elevated STIM1 protein levels. These results reveal that mutation in the dystrophin-encoding Dmd gene may significantly impact cellular calcium response to metabotropic stimulation involving depletion of the intracellular calcium stores followed by activation of the store-operated calcium entry, as early as in undifferentiated myoblasts. These data are in agreement with the increasing number of reports showing that the dystrophic pathology resulting from dystrophin mutations may be developmentally regulated. Moreover, our results showing that aberrant responses to extracellular stimuli may contribute to DMD pathogenesis suggest that treatments inhibiting such responses might alter progression of this lethal disease

Diversité et origine génétique des espèces de la sous famille des Aurantioideae et décryptage des structures interspécifiques des génomes des agrumes modernes

L'étude de l'espaceur intergénique tmL-tmF chez les espèces tunisiennes du genre Citrus montre la présence d'une seule copie du pseudogène tmF chez toutes les variétés analysées. Les valeurs positives et non significatives des tests de neutralité plaident en faveur d'un modèle d'évolution neutre et supportent l'hypothèse d'un scénario démographique stable. Nos résultats montrent clairement la contribution des pools génétiques de C. reticulata et C. maxima dans le développement des espèces secondaires tunisiennes. L'analyse basée sur les séquences nucléotidiques de huit régions génomiques chloroplastiques de 79 variétés de la sous famille des Aurantioideae révèle, via les marqueurs SNPs, une différenciation taxonomique au niveau des tribus, des soustribus, des genres et des espèces. 166 SNPs diagnostiques des 54 clades analysés ont été identifiés suivis d'une sélection de 40 KASPars. L'application de ces marqueurs chez 108 variétés montre un haut taux de transférabilité au sein de la sous famille des Aurantioideae et une cohérence avec les analyses génétiques antérieures du génome chloroplastique 21 clés marqueurs de clade catégoriquement diagnostique de 19 clades ont été identifiées. L'analyse GBS des 55 variétés d'agrumes par séquençage ILLUMINA H1SEQ2000 s'avère efficace dans d'identification des polymorphismes diagnostiques (12564 SNPs/lnDels) de la différenciation C. reticulata/C. maxima couvrant l'ensemble du génome nécessaire au déchiffrage de l'origine phylogénomique tout au long des neuf chromosomes des 55 variétés. L'approche adoptée confirme les analyses récentes basées sur des données de séquence de génome complet pour la clémentine, l'orange douce et amère et la mandarine 'Ponkan'. La technique GBS couplée à la détection des points polymorphes diagnostiques s'avère très efficace dans le décryptage des caryotypes phylogénomiques des variétés qui dérivent d'une mosaïque de deux espèces ancestrales. Le mélange C. reticulata/C. maxima doit être l'élément majeur de la variabilité phénotypique révélée élevée de ces ressources. (Résumé d'auteur

Hospital treatment in Poland during the transformation period. An attempt to evaluate the activities of public and non-public hospitals in the organizational and economic sphere based on the performance card model

Celem artykułu jest przedstawienie i podsumowanie ewolucji form organizacyjnych szpitali i ich sytuacji finansowej na tle procesu transformacji polskiego systemu opieki zdrowotnej do momentu zmian systemowych wprowadzonych pakietem ustaw zdrowotnych w latach 2010–2011. Szczególna uwaga zwrócona została na potrzebę wypracowania jednolitego, dla jednostek publicznych i niepublicznych, systemu pomiaru dokonań oraz dostosowanego do jego wymagań systemu sprawozdawczości szpitali. Uwzględniając specyfikę szpitali niepublicznych w kontekście propozycji wdrożenia modelu karty dokonań na potrzeby zintegrowanego systemu oceny działalności szpitali publicznych, wskazano obszary zmian, niezbędnych w ocenie autorów, dla ujednolicenia systemu oceny.The aim of the article is to present and summarize the evolution of forms of organization of hospitals and their financial situation against the background of the process of transformation of the Polish health care system functioning until the system changes made by a package of laws of health in 2010–2011. Particular attention has been paid to the need to develop a homogeneous system for public and non-public entities to measure achievements and, tailored to its requirements, a reporting system for hospitals. Taking into account the specificity of non-public hospitals in the context of a proposal for implementing the model of achievement cards for integrated assessment of the activities of public hospitals the authors have identified areas of – in their opinion – necessary changes to harmonize the assessment system

Metabolism and toxicity of cadmium in humans and animals

Cadmium (Cd(II)) is one of the most important toxic chemicals due to its increasing level in the environment as a result of industrial and agricultural practices. Cd(II) has a very long biological half-life (10-30 years) in humans and its toxicity is dependent on the dose, route and duration of exposure. Cd(II) is absorbed from the gastro-intestinal tract primarily by utilizing transporters for essential elements such as iron and zinc, as well as calcium channels. In this review multiple mechanisms of Cd(II) toxicity are discussed, such as interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species, modulation of signal transduction and gene expression, inhibition of DNA repair and DNA methylation, and disruption of E-cadherin-mediated cell-cell adhesion. The role of Cd(II) in apoptosis is also discussed

Details of antibodies used in the study.

<p>Details of antibodies used in the study.</p

Risankizumab Therapy for Moderate-to-Severe Psoriasis—A Multi-Center, Long-Term, Real-Life Study from Poland

The present multi-center, long-term, real-life study made an attempt to assess the efficacy of risankizumab in the treatment of moderate-to-severe plaque psoriasis. The study comprised 185 patients from 10 Polish dermatologic departments undergoing risankizumab treatment. The disease severity was measured using the Psoriasis Area and Severity Index (PASI) before the start of the risankizumab treatment and next at the defined timepoints, i.e., 4, 16, 28, 40, 52 and 96 weeks of treatment. The percentage of patients achieving PASI90 and PASI100 responses as well as the PASI percentage decrease at the defined timepoints were calculated, and correlations with clinical characteristics and therapeutic effect were analyzed. The number of patients evaluated at the defined timepoints was: 136, 145, 100, 93, 62, and 22 at 4, 16, 28, 40, 52 and 96 weeks of treatment, respectively. At 4, 16, 28, 40, 52 and 96 weeks, the PASI90 response was achieved in 13.2%, 81.4%, 87.0%, 86.0%, 88.7% and 81.8% of patients, whereas the PASI100 response was achieved in 2.9%, 53.1%, 67.0%, 68.8%, 71.0% and 68.2% of patients, respectively. Our study revealed a significant negative correlation between a decrease in the PASI and the presence of psoriatic arthritis as well as the patient’s age and duration of psoriasis at several timepoints throughout the observation period