Biallelic mutation of UNC50, encoding a protein involved in AChR trafficking, is responsible for arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Homozygosity mapping of disease loci combined with whole exome sequencing in a consanguineous family presenting with lethal AMC allowed the identification of a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.

pHAST (pH-Driven Aptamer Switch for Thrombin) Catch-and-Release of Target Protein.

A pH-driven DNA nanomachine based on the human α-thrombin binding aptamer was designed for the specific catch-and-release of human α-thrombin at neutral and acidic pH, respectively. In neutral conditions, the thrombin aptamer component of the nanomachine is exposed and exists in the G-quadruplex conformation required to bind to the target protein. At slightly acidic pH, the polyadenine tail of the nanomachine becomes partially protonated and A+(anti)•G(syn) mispairing results in a conformational change, causing the target protein to be released.

Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis.

Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy has a specific morphological phenotype.

Effects of training at mild exercise intensities on quadriceps muscle energy metabolism in patients with chronic obstructive pulmonary disease.

Aim: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects.

Methods: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities.

Results: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects.

Benefits of home-based endurance training in lung transplant recipients.

Background: To investigate the effect of home-based exercise training on exercise tolerance, muscle function and quality of life in lung transplant recipients (LTR).

Methods: Twelve LTR and 7 age-matched healthy subjects underwent exercise training (ET, 12-wk, 3×/wk, 40 min). Peak aerobic capacity VO2peak, endurance time (T(end)), minute ventilation (VE) quadriceps strength, percentage of type I fiber (%Ifb), fiber diameters and chronic respiratory questionnaire were assessed before and after ET.

Infection kinetics of human adenovirus serotype 41 in HEK 293 cells.

The purpose of this work was to acquire an overview of the infectious cycle of HAdV-41 in permissive HEK 293 cells and compare it to that observed with the prototype of the genus, Human adenovirus C HAdV-2. HEK 293 cells were infected with each virus separately and were harvested every 12 h for seven days. Infection kinetics were analysed using confocal and electronic microscopy.

Effects of chronic treatment with a low dose of nicorandil on the function of the rat aorta during ageing.

1. It is known that ATP-sensitive potassium (K(ATP)) channels regulate the membrane potential of smooth muscle cells and vascular tone. Because their activity is altered during ageing, many pharmacological treatments aimed at improving K(ATP) channel and cardiovascular functions have been evaluated.

Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy.

While TPM2 mutations identified so far in muscular diseases were all associated with a dominant inheritance pattern, we report the identification of a homozygous null allele mutation in the TPM2 gene in a patient who presented with a recessive form of nemaline myopathy associated with a non-lethal multiple pterygium syndrome (Escobar-MPS MIM# 265000). The TPM2 mutation led to a complete absence of the skeletal muscle isoform of beta-tropomyosin not compensated by expression of other beta-tropomyosin isoforms. Escobar syndrome has been recently described as a prenatal form of myasthenia associated with recessive mutations in genes of the neuromuscular junction (CHRNG, CHRNA1, CHRND, RAPSN).

Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells.

Cytotoxic T lymphocytes (CTL) are crucial in viral clearance and tumor growth control. Thus the induction of CTL activity is an important aim in vaccine development. We investigate an innovative delivery system for peptide transfer to the MHC class I processing pathway of APC with the aim to trigger CTL in the context of an antitumoral response.

Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.

Malignant hyperthermia susceptibility (MHS) is a subclinical pharmacogenetic disorder caused by an impairment of skeletal muscle calcium homeostasis in response to triggering agents. While in vitro contracture testing (IVCT) is the gold standard for defining MHS, molecular analysis is increasingly used to diagnosis MHS. Mutations associated with MHS have been reported in two genes: RYR1 and CACNA1S.

Synthesis, cellular localization, and quantification of penton-dodecahedron in serotype 3 adenovirus-infected cells.

Adenovirus penton is a non-covalent complex composed of the penton base and fiber proteins, localized at the twelve vertices of the icosahedral virus capsid. In cells infected by adenovirus serotype 3 (Ad3), penton is found not only in the virus capsid but also self-assembled in dodecahedra formed through interactions between the twelve penton bases. In this study, the intracellular trafficking of penton proteins from the cytoplasm to the nucleus has been followed, and the nuclear re-arrangement induced by viral infection has been observed by electron microscopy of ultrathin sections.

Functional coupling of adenine nucleotide translocase and mitochondrial creatine kinase is enhanced after exercise training in lung transplant skeletal muscle.

Mechanisms responsible for limitation of exercise capacity in lung transplant recipients (LR) and benefits gained by exercise training were studied. Mitochondrial respiration parameters, energy transfer, and cell structure were assessed in vastus lateralis biopsies using the permeabilized fiber technique with histochemical and morphometric measurements. Twelve male controls (C) and 12 LR performed exercise training over 12 wk.

Toxicity of the Clitocybe amoenolens mushroom in the rat.

Ingestion of Clitocybe amoenolens, a mushroom collected in Savoie (France), induced erythermalgia in 5 patients. To assess C. amoenolens toxicity, increasing doses were given randomly to 4 rats corresponding to 1 to 25 fold the dose eaten by the most severely poisoned patient.

A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.

The ryanodine receptor (RYR1) is an essential component of the calcium homeostasis of the skeletal muscle in mammals. Inactivation of the RYR1 gene in mice is lethal at birth. In humans only missense and in-frame mutations in the RYR1 gene have been associated so far with various muscle disorders including malignant hyperthermia, central core disease and the moderate form of multi-minicore disease (MmD).

Histological support for the difference between malignant hyperthermia susceptible (MHS), equivocal (MHE) and negative (MHN) muscle biopsies.

The aim of this study was to find, using modern techniques, any histological differences in muscle biopsies between malignant hyperthermia (MH) susceptible (MHS), MH equivocal (MHE) and MH negative (MHN) patients. On the basis of the European MH contracture test carried out in 83 patients, 23 were shown to be MHS, nine MHE and 51 MHN. Four lesions were found with a significantly high frequency in MHS and MHE biopsies: muscle fibre hypertrophy and atrophy, internal nuclei and myofibrillar necrosis.

Presence of zinc and calcium permeant channels in the inner membrane of the nuclear envelope.

The nuclear envelope possesses specific ion channels that regulate the ionic traffic between the cytoplasm or the perinuclear space and the nucleoplasm. Using the patch-clamp technique to isolated rat nuclei exhibiting only the inner membrane of the nuclear envelope, we report the existence of calcium and zinc permeant channels. These channels displayed similar characteristics (conductance : 8 and 11 pS respectively, open time constant (3.

In vitro 31P-magnetic resonance spectroscopy of muscle extracts in malignant hyperthermia-susceptible patients.

Background: It was recently suggested that malignant hyperthermia-susceptible (MHS) patients could have an elevated peak of phosphodiesters in leg muscles using in vivo phosphorus magnetic resonance spectroscopy. In the current study, analysis of the phosphodiesters of muscle extracts of MHS and malignant hyperthermia-negative patients was performed using in vitro phosphorus magnetic resonance spectroscopy to chemically identify and to compare the muscle concentrations of water-soluble compounds between the two groups with respect to the muscle fiber type composition.

Methods: Perchloric acid extracts of the vastus medialis muscle of seven MHS patients and ten malignant hyperthermia-negative patients on the basis of the European malignant hyperthermia contracture test were subjected to in vitro phosphorus magnetic resonance spectroscopy carried out at 9.

Contribution of apoptosis to the phenotypic changes of adrenocortical cells in primary culture.

The aim of this study was to evaluate the occurrence and physiological consequences of apoptosis in primary cultures of bovine adrenocortical cells (of fasciculata-reticularis origin). Under ACTH-free culture conditions, we observed apoptotic cells in the cell layer and the accumulation of apoptotic bodies in the culture medium. These were hardly detectable in ACTH-supplemented cultures.

Morphometric analysis of the peripheral nerve: advantages of the semi-automated interactive method.

A semi-automated interactive method (BIOCOM) was developed for the morphometric analysis of the peripheral nerve in routine histopathological examination. The human superficial peroneal nerve was used for myelinated fibre measurements. The precision and reproducibility of the results were validated using a manual morphometric method on a digitalizing table.

[Churg-Strauss syndrome with rectal localization and exudative enteropathy].

The authors report the case of a 61-year old patient with a Churg-Strauss syndrome revealed by abdominal pain. Investigations showed a diffuse inflammatory digestive tract involvement, documented by endoscopy associated with protein-losing enteropathy. Deep rectal biopsy revealed vasculitis in an otherwise macroscopically normal rectum.

Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve.

In this study we determined the ultrastructural distribution of the various components of the extracellular matrix (laminin, fibronectin, Type I, III, and IV collagens) of the normal peripheral nerve in adult rat. The localization of these macromolecules was investigated in basement membranes as well as in different areas of epi-, peri-, and endoneurium, by use of a pre-embedding immunoperoxidase method.