RNA binding protein RALY promotes Protein Arginine Methyltransferase 1 alternatively spliced isoform v2 relative expression and metastatic potential in breast cancer cells.

Aberrant expression of Protein Arginine Methyltransferases (PRMTs) has been observed in several cancer types, including breast cancer. We previously reported that the PRMT1v2 isoform, which is generated through inclusion of alternative exon 2, is overexpressed in breast cancer cells and promotes their invasiveness. However, the precise mechanism by which expression of this isoform is controlled and how it is dysregulated in breast cancer remains unknown.

Human adenovirus type 5 vectors deleted of early region 1 (E1) undergo limited expression of early replicative E2 proteins and DNA replication in non-permissive cells.

Adenovirus (Ad) vectors deleted of the early region 1 (E1) are widely used for transgene delivery in preclinical and clinical gene therapy studies. Although proteins encoded within the E1 region are required for efficient virus replication, previous studies have suggested that certain viral or cellular proteins can functionally compensate for E1, leading to expression of the early region 2 (E2)-encoded replicative proteins and subsequent virus replication. We have generated a series of E1-encoding and E1-deficient Ad vectors containing a FLAG-epitope tag on each of the E2-encoded proteins: DNA-binding protein (DBP), terminal protein (TP) and DNA polymerase (Pol).

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation.

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by motor neuron degeneration, although defects in multiple cell types and tissues have also been implicated. Three independent laboratories recently identified immune organ defects in SMA. We therefore propose a novel pathogenic mechanism contributory to SMA, resulting in higher susceptibility to infection and exacerbated disease progression caused by neuroinflammation.

In Vivo Assessment of Engineered Skin Cell Delivery with Multimodal Optical Microscopy.

The healing process is often significantly impaired under conditions of chronic or large area wounds, which are often treated clinically using autologous split-thickness skin grafts. However, in many cases, harvesting of donor tissue presents a serious problem such as in the case of very large area burns. In response to this, engineered biomaterials have emerged that attempt to mimic the natural skin environment or deliver a suitable therapy to assist in the healing process.

Skeletal Muscle Remodeling: Interconnections Between Stem Cells and Protein Turnover.

Nutrition and exercise are important components of a healthy lifestyle to improve rates of hypertrophic and nonhypertrophic skeletal muscle remodeling. We provide evidence to support the hypothesis that muscle stem cells and protein turnover are collaborative, not separate, mechanisms supporting muscle remodeling by facilitating protein, nuclear, and cellular turnover in response to the ingestion of protein dense foods and exercise.

Muscle-specific expression of the RNA-binding protein Staufen1 induces progressive skeletal muscle atrophy via regulation of phosphatase tensin homolog.

Converging lines of evidence have now highlighted the key role for post-transcriptional regulation in the neuromuscular system. In particular, several RNA-binding proteins are known to be misregulated in neuromuscular disorders including myotonic dystrophy type 1, spinal muscular atrophy and amyotrophic lateral sclerosis. In this study, we focused on the RNA-binding protein Staufen1, which assumes multiple functions in both skeletal muscle and neurons.

Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in gene.

Objective: To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation.

Methods: Twenty-nine Finnish patients identified with the c.

Measuring Habitual Physical Activity in Neuromuscular Disorders: A Systematic Review.

Background: Free-living or habitual physical activity (HPA) refers to someone's performance in his or her free-living environment. Neuromuscular disorders (NMD) manifest through HPA, and the observation of HPA can be used to identify clinical risks and to quantify outcomes in research. This review summarizes and analyses previous studies reporting the assessment of HPA in NMD, and may serve as the basis for evidence-based decision-making when considering assessing HPA in this population.

Whole-transcriptome sequencing in blood provides a diagnosis of spinal muscular atrophy with progressive myoclonic epilepsy.

At least 15% of the disease-causing mutations affect mRNA splicing. Many splicing mutations are missed in a clinical setting due to limitations of in silico prediction algorithms or their location in noncoding regions. Whole-transcriptome sequencing is a promising new tool to identify these mutations; however, it will be a challenge to obtain disease-relevant tissue for RNA.

Hematopoiesis with Obesity and Exercise: Role of the Bone Marrow Niche.

Hematopoietic stem and progenitor cells (HSPC), the most primitive cells of the hematopoietic system responsible for maintaining all mature blood cells, display the hallmark characteristics of self-renewal and multi-potent differentiation into mature cell lineages. HSPC activity is directed by the bone marrow niche, a complex environment composed of heterogeneous cell populations that regulate HSPC function through the secretion of a wide array of cytokines and growth factors. Diet induced obesity results in a dramatic remodeling of the bone marrow niche, skewing HSPC function resulting in a compromised immune system.

Novel Roles for Staufen1 in Embryonal and Alveolar Rhabdomyosarcoma via c-myc-dependent and -independent events.

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes.

Effect of genetic background on the phenotype of the Smn2B/- mouse model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is caused by mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene in humans. Modifiers of the SMA symptoms have been identified and genetic background has a substantial effect in the phenotype and survival of the severe mouse model of SMA. Previously, we generated the less severe Smn2B/- mice on a mixed genetic background.

Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA.

Adenoviral Vectors Armed with Cell Fusion-Inducing Proteins as Anti-Cancer Agents.

Cancer is a devastating disease that affects millions of patients every year, and causes an enormous economic burden on the health care system and emotional burden on affected families. The first line of defense against solid tumors is usually extraction of the tumor, when possible, by surgical methods. In cases where solid tumors can not be safely removed, chemotherapy is often the first line of treatment.

Kinetics of circulating progenitor cell mobilization during submaximal exercise.

Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs) that are involved in tissue repair and adaptation. CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors.

Oligodendrocyte development and CNS myelination are unaffected in a mouse model of severe spinal muscular atrophy.

The childhood neurodegenerative disease spinal muscular atrophy (SMA) is caused by loss-of-function mutations or deletions in the Survival Motor Neuron 1 (SMN1) gene resulting in insufficient levels of survival motor neuron (SMN) protein. Classically considered a motor neuron disease, increasing evidence now supports SMA as a multi-system disorder with phenotypes discovered in cortical neuron, astrocyte, and Schwann cell function within the nervous system. In this study, we sought to determine whether Smn was critical for oligodendrocyte (OL) development and central nervous system myelination.

Muscle-specific microRNA-206 targets multiple components in dystrophic skeletal muscle representing beneficial adaptations.

Over the last several years, converging lines of evidence have indicated that miR-206 plays a pivotal role in promoting muscle differentiation and regeneration, thereby potentially impacting positively on the progression of neuromuscular disorders, including Duchenne muscular dystrophy (DMD). Despite several studies showing the regulatory function of miR-206 on target mRNAs in skeletal muscle cells, the effects of overexpression of miR-206 in dystrophic muscles remain to be established. Here, we found that miR-206 overexpression in mdx mouse muscles simultaneously targets multiple mRNAs and proteins implicated in satellite cell differentiation, muscle regeneration, and at the neuromuscular junction.

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.

Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD) synthesis, consistent with a potential role for the essential cofactor NAD in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD and are involved in pleiotropic events, including inflammation.

Expression of the fusogenic p14 FAST protein from a replication-defective adenovirus vector does not provide a therapeutic benefit in an immunocompetent mouse model of cancer.

When injected directly into a tumor mass, adenovirus (Ad) vectors only transduce cells immediately along the injection tract. Expression of fusogenic proteins from the Ad vector can lead to syncytium formation, which efficiently spreads the therapeutic effect. Fusogenic proteins can also cause cancer cell death directly, and enhance the release of exosome-like particles containing tumor-associated antigens, which boosts the anti-tumor immune response.

Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome.

Bing Neel syndrome is a rare disease manifestation of Waldenström's macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies, that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and includes headaches, cognitive deficits, paresis, and psychiatric symptoms.

Opening the window: The case for carrier and perinatal screening for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease that leads to infant mortality worldwide. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in a deficiency in SMN protein. For reasons that are still unclear, SMN protein deficiency predominantly affects α-motor neurons, resulting in their degeneration and subsequent paralysis of limb and trunk muscles, progressing to death in severe cases.

Differential induction of muscle atrophy pathways in two mouse models of spinal muscular atrophy.

Motor neuron loss and neurogenic atrophy are hallmarks of spinal muscular atrophy (SMA), a leading genetic cause of infant deaths. Previous studies have focused on deciphering disease pathogenesis in motor neurons. However, a systematic evaluation of atrophy pathways in muscles is lacking.

A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia.

Episodic ataxia type 1 (EA1) is an autosomal dominant channelopathy caused by mutations in KCNA1, which encodes the voltage-gated potassium channel, Kv1.1. Eleven members of an EA family were evaluated with molecular and functional studies.