Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish.

Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology.

Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes.

Mammalian cardiomyocytes become post-mitotic shortly after birth. Understanding how this occurs is highly relevant to cardiac regenerative therapy. Yet, how cardiomyocytes achieve and maintain a post-mitotic state is unknown.

Organ-specific function of adhesion G protein-coupled receptor GPR126 is domain-dependent.

Despite their abundance and multiple functions in a variety of organ systems, the function and signaling mechanisms of adhesion G protein-coupled receptors (GPCRs) are poorly understood. Adhesion GPCRs possess large N termini containing various functional domains. In addition, many of them are autoproteolytically cleaved at their GPS sites into an N-terminal fragment (NTF) and C-terminal fragment.

The functional properties of nephronectin: an adhesion molecule for cardiac tissue engineering.

Despite significant advances in preventive cardiovascular medicine and therapy for acute and chronic heart failure, cardiovascular diseases remain among the leading causes of death worldwide. In recent years cardiac tissue engineering has been established as a possible future treatment option for cardiac disease. However, the quality of engineered myocardial tissues remains poor.

Modulation of the glyoxalase system in the aging model Podospora anserina: effects on growth and lifespan.

The eukaryotic glyoxalase system consists of two enzymatic components, glyoxalase I (lactoylglutathione lyase) and glyoxalase II (hydroxyacylglutathione hydrolase). These enzymes are dedicated to the removal of toxic α-oxoaldehydes like methylglyoxal (MG). MG is formed as a by-product of glycolysis and MG toxicity results from its damaging capability leading to modifications of proteins, lipids and nucleic acids.

Genome-wide association study of intracranial aneurysm identifies three new risk loci.

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.

The mitochondrial kinase PINK1, stress response and Parkinson's disease.

Mitochondrial dysfunction is well documented in presymptomatic brain tissue with Parkinson's disease (PD). Identification of the autosomal recessive variant PARK6 caused by loss-of-function mutations in the mitochondrial kinase PINK1 provides an opportunity to dissect pathogenesis. Although PARK6 shows clinical differences to PD, the induction of alpha-synuclein "Lewy" pathology by PINK1-deficiency proves that mitochondrial pathomechanisms are relevant for old-age PD.

Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.

Background: Parkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD.

Methodology/principal Findings: Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age.

Parkinson patient fibroblasts show increased alpha-synuclein expression.

Parkinson's disease (PD) is a neurodegenerative movement disorder of advanced age with largely unknown etiology, but well documented tissue damage from oxidative stress. Increased alpha-synuclein (SNCA) expression is known to cause a rare form of PD, early-onset autosomal dominant PARK4. We have previously shown that loss-of-function mutations of the mitochondrial kinase PINK1 which cause the early-onset recessive PARK6 variant result in oxidative damage in patient fibroblasts.