A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?

Despite the fact that there are published case reports and model work providing evidence of inflammation in Charcot-Marie-Tooth disorders (CMTs), in clinical practice, CMT and inflammatory neuropathies are always classified as two separate groups of disorders. This sharp separation of chronic neuropathies into two groups has serious clinical implications. As a consequence, the patients harboring CMT mutations are practically excluded from pharmacological anti-inflammatory treatments.

Bacterial Emission Factors: A Foundation for the Terrestrial-Atmospheric Modeling of Bacteria Aerosolized by Wildland Fires.

Wildland fire is a major global driver in the exchange of aerosols between terrestrial environments and the atmosphere. This exchange is commonly quantified using emission factors or the mass of a pollutant emitted per mass of fuel burned. However, emission factors for microbes aerosolized by fire have yet to be determined.

Climate warming increases extreme daily wildfire growth risk in California.

California has experienced enhanced extreme wildfire behaviour in recent years, leading to substantial loss of life and property. Some portion of the change in wildfire behaviour is attributable to anthropogenic climate warming, but formally quantifying this contribution is difficult because of numerous confounding factors and because wildfires are below the grid scale of global climate models. Here we use machine learning to quantify empirical relationships between temperature (as well as the influence of temperature on aridity) and the risk of extreme daily wildfire growth (>10,000 acres) in California and find that the influence of temperature on the risk is primarily mediated through its influence on fuel moisture.

The GDAP1 p.Glu222Lys Variant-Weak Pathogenic Effect, Cumulative Effect of Weak Sequence Variants, or Synergy of Both Factors?

Charcot−Marie−Tooth disorders (CMT) represent a highly heterogeneous group of diseases of the peripheral nervous system in which more than 100 genes are involved. In some CMT patients, a few weak sequence variants toward other CMT genes are detected instead of one leading CMT mutation. Thus, the presence of a few variants in different CMT-associated genes raises the question concerning the pathogenic status of one of them.

Validation of the Pathogenic Effect of Gene Mutations Based on Yeast Model.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a heritable neurodegenerative disease characterized by rapid respiratory failure within the first months of life and progressive muscle weakness and wasting. Although the causative gene, , is well defined, information on mutations is not always sufficient to diagnose particular patients, as the gene is highly polymorphic and the pathogenicity of many gene variants is unknown. In this study, we generated a simple yeast model to establish the significance of variants for disease development, especially those that are missense mutations.

Analysis of the Innovative Channel Strut Concept Manufactured by Roll-Forming.

Due to the wide use of channel strut components, manufacturing is implemented in many industrial plants. Standard technology of profiles is based on welding of two parts of the profile and requires the regalvanizing of the joint zone causes. Thus, the production is challenging to automate on a single line.

Models for IGHMBP2-associated diseases: an overview and a roadmap for the future.

Models are practical tools with which to establish the basic aspects of a diseases. They allow systematic research into the significance of mutations, of cellular and molecular pathomechanisms, of therapeutic options and of functions of diseases associated proteins. Thus, disease models are an integral part of the study of enigmatic proteins such as immunoglobulin mu-binding protein 2 (IGHMBP2).

Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation.

Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation.

Mutations in Influence Structure and Function of the Trans-Golgi Network.

Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative disease that displays great genetic heterogeneity. The genes and mutations that underlie this heterogeneity have been extensively characterized by molecular genetics. However, the molecular pathogenesis of the vast majority of CMT subtypes remains terra incognita.

Recommendations on the diagnosis of male infertility - genetic testing [Rekomendacje dotyczące diagnostyki genetycznej w niepłodności męskiej].

Male infertility is the cause of couples' infertility in about 50% of cases. Current recommendations on the diagnosis and treatment of male infertility advance thorough medical history taking and physical examination, to provide the basis for further genetic evaluation. The extent of genetic testing itself depends on the semen analysis results, which allow the risk of inheritance of chromosomal aberrations to be determined and the root causes of habitual miscarriages to be explained.

Application of the Numerical Model to Design the Geometry of a Unit Tool in the Innovative RTH Hydroforming Technology.

The article presents a newly patented rapid tube hydroforming (RTH) manufacturing method, perfectly suited to single-piece production. The RTH technology significantly complements the scope of hydroforming processes. Due to the unusual granular material of the die tool, in particular moulding sand or mass, the process design requires the use of numerical modelling calculations.

The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on .

Objective: To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained neuropathies in the elderly, we performed genetic analysis of 230 patients with unexplained axonal neuropathies and disease onset ≥35 years.

Methods: We recruited patients, collected clinical data, and conducted whole-exome sequencing (WES; n = 126) and single-gene sequencing (n = 104). We further queried WES repositories for variants and measured blood levels of the -encoded protein neprilysin.

Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.

Background And Purpose: Charcot-Marie-Tooth disease type 1 (CMT1) is a group of autosomal dominantly inherited demyelinating sensorimotor neuropathies. Symptoms usually start in the first to second decade and include distal muscle weakness and wasting, sensory disturbances and foot deformities. The most frequent cause is a duplication of PMP22 whilst point mutations in PMP22 and other genes are rare causes.

A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases.

Charcot-Marie-Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed.

Pathogenic Effect of Gene Mutations in a Yeast Model.

The question of whether a newly identified sequence variant is truly a causative mutation is a central problem of modern clinical genetics. In the current era of massive sequencing, there is an urgent need to develop new tools for assessing the pathogenic effect of new sequence variants. In Charcot-Marie-Tooth disorders (CMT) with their extreme genetic heterogeneity and relatively homogenous clinical presentation, addressing the pathogenic effect of rare sequence variants within 80 CMT genes is extremely challenging.

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs.

Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer a means to deliver behavioral, psychosocial, disease self-management and music-based interventions to improve therapy outcomes for chronic diseases, including pain and epilepsy. To explore new translational opportunities in developing digital therapeutics for neurological disorders, and their integration with pharmacotherapies, we examined analgesic and antiseizure effects of specific musical compositions in mouse models of pain and epilepsy. The music playlist was created based on the modular progression of Mozart compositions for which reduction of seizures and epileptiform discharges were previously reported in people with epilepsy.

[Therapeutic perspective in hereditary polyneuropathies].

Hereditary motor and sensory neuropathies (HMSN) also called as Charcot-Marie-Tooth disorders (CMT) are extremely heterogeneous group of disorders of peripheral nervous system. Over 80 genes have been reported in different types of CMT. In all CMT affected patients the main symptoms are slowly progressive wasting of the distal muscles of the lower and upper limbs.

The Fire and Smoke Model Evaluation Experiment-A Plan for Integrated, Large Fire-Atmosphere Field Campaigns.

The Fire and Smoke Model Evaluation Experiment (FASMEE) is designed to collect integrated observations from large wildland fires and provide evaluation datasets for new models and operational systems. Wildland fire, smoke dispersion, and atmospheric chemistry models have become more sophisticated, and next-generation operational models will require evaluation datasets that are coordinated and comprehensive for their evaluation and advancement. Integrated measurements are required, including ground-based observations of fuels and fire behavior, estimates of fire-emitted heat and emissions fluxes, and observations of near-source micrometeorology, plume properties, smoke dispersion, and atmospheric chemistry.

Fire behavior and smoke modeling: Model improvement and measurement needs for next-generation smoke research and forecasting systems.

There is an urgent need for next-generation smoke research and forecasting (SRF) systems to meet the challenges of the growing air quality, health, and safety concerns associated with wildland fire emissions. This review paper presents simulations and experiments of hypothetical prescribed burns with a suite of selected fire behavior and smoke models and identifies major issues for model improvement and the most critical observational needs. The results are used to understand the new and improved capability required for the next-generation SRF systems and to support the design of the Fire and Smoke Model Evaluation Experiment (FASMEE) and other field campaigns.

Molecular modelling of mitofusin 2 for a prediction for Charcot-Marie-Tooth 2A clinical severity.

Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant neuropathy caused by mutations in the mitofusin 2 gene (MFN2). More than 100 MFN2 gene mutations have been reported so far, with majority located within the GTPase domain encoding region. These domain-specific mutations present wide range of symptoms with differences associated with distinct amino acid substitutions in the same position.

Charcot‑Marie‑Tooth type 1A drug therapies: role of adenylyl cyclase activity and G‑protein coupled receptors in disease pathomechanism.

Charcot‑Marie‑Tooth type 1A (CMT1A) is a dysmyelinating disease of the peripheral nervous system that results in a slow progressive weakening and wasting of the distal muscles of the upper and lower limbs. Despite extensive research and clinical trials there is still no treatment for CMT1A that results in complete neurological improvement. Recent studies investigating various pharmacological modulators of adenylyl cyclase activity, including ascorbic acid and ligands of G protein‑coupled receptors (GPCRs), provide hope for future treatments of this type of hereditary motor and sensory neuropathy.

A role for the GDAP1 gene in the molecular pathogenesis of Charcot‑Marie‑Tooth disease.

In 2002 a series of mutations in the GDAP1 gene were reported in patients suffering from Charcot‑Marie‑Tooth disease manifesting as early-onset, progressive distal‑muscle wasting and weakness. The molecular etiology of Charcot‑Marie‑Tooth ‑GDAP1 disease has been elucidated but its pathogenesis remains unclear, especially given the seemingly contradictory function of the GDAP1 protein. Expression of GDAP1 is observed almost exclusively in neuronal cells, however, the GDAP1 protein is present in mitochondria, where it plays a role in fission, a ubiquitous process occurring in all cells.

A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy - a case report and review of the genotype-phenotype correlation.

Collagen VI-related myopathy is a group of disorders affecting skeletal muscles and connective tissue. The most common symptoms are muscle weakness and joint deformities which limit the movement and progress over time. Several forms of collagen VI-related myopathies have been described: Bethlem myopathy, an intermediate form and Ullrich congenital muscular dystrophy, which is the most severe.