A5051048629- Hereditary Neurological Disorders
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Signaling Pathways in Disease
- Gastrointestinal motility and disorders
- Neuropeptides and Animal Physiology
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Muscle Physiology and Disorders
- Microtubule and mitosis dynamics
- Neurological diseases and metabolism
- Hepatitis C virus research
- Erythrocyte Function and Pathophysiology
- Toxin Mechanisms and Immunotoxins
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- HIV/AIDS drug development and treatment
- Genetic Neurodegenerative Diseases
- Botulinum Toxin and Related Neurological Disorders
- Ubiquitin and proteasome pathways
- Neuroendocrine regulation and behavior
- Neuroscience and Neuropharmacology Research
- Herpesvirus Infections and Treatments
- Congenital gastrointestinal and neural anomalies
- RNA Research and Splicing
University of Edinburgh
2012-2021
Discovery Centre
2019-2021
Universitätsklinikum Würzburg
2018
Cyprus Institute of Neurology and Genetics
2018
Bristol-Myers Squibb (United States)
2014
Bristol-Myers Squibb (United Kingdom)
2014
Mossakowski Medical Research Institute, Polish Academy of Sciences
2006
Medical University of Warsaw
2006
Polish Academy of Sciences
2006
Icahn School of Medicine at Mount Sinai
1995
All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue NS5B polymerase in infected genotype 1, 2, or 3.In this open-label study, we initially randomly assigned 44 previously untreated 1 infection and 2 3 to at a dose of 60 mg orally once daily 400 daily, without ribavirin, 24 weeks. The study was expanded include 123 additional who were...
Two major isoforms of the cell adhesion molecule neurofascin NF186 and NF155 are expressed in central nervous system (CNS). We have investigated their roles assembly node Ranvier show that they targeted to distinct domains at node. At onset myelination, is restricted neurons, whereas localizes oligodendrocytes, myelin-forming glia CNS. Coincident with axon ensheathment, clusters paranodal regions myelin sheath where it apposition axonal paranodin/contactin-associated protein (Caspr1), which...
Previous studies (Blank, W. F., M. B. Bunge, and R. P. Bunge. 1974. Brain Res. 67:503-518) showed that Schwann cell paranodal membranes were disrupted in calcium free medium suggesting cadherin mediated mechanisms may operate to maintain the integrity of membrane complex. Using antibodies against fifth extracellular domain E-cadherin, we now show by confocal laser electron immunomicroscopy E-cadherin is a major adhesive glycoprotein peripheral nervous system cells. E-Cadherin not found,...
The maturation and envelopment of varicella-zoster virus (VZV) was studied in infected human embryonic lung fibroblasts. Transmission electron microscopy confirmed that nucleocapsids acquire an envelope from the inner nuclear membrane as they enter perinuclear-cisterna-rough endoplasmic reticulum (RER). Tegument is not detectable these virions; moreover, contrast to mature VZV envelope, RER radioautographically labeled pulse-chase experiments with [3H]mannose, it lacks gpI immunoreactivity...
Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes Ranvier. Myelin-forming oligodendrocytes central nervous system (CNS) induce clustering into nodal complexes flanked by paranodal axoglial junctions. However, molecular mechanisms for complex assembly CNS are unknown. Two isoforms Neurofascin, neuronal Nfasc186 and glial Nfasc155, components complexes, respectively. Neurofascin-null mice have disrupted complexes. We show...
The axon initial segment (AIS) is critical for the initiation and propagation of action potentials. Assembly AIS requires interactions between scaffolding molecules voltage-gated sodium channels, but molecular mechanisms that stabilize are poorly understood. neuronal isoform Neurofascin, Nfasc186, clusters channels at nodes Ranvier in myelinated nerves: here, we investigate its role assembly stabilization. Inactivation Nfasc gene cerebellar Purkinje cells adult mice causes rapid loss...
In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. recent years, there has been an increased understanding the extracellular intracellular factors that initiate stimulate cell myelination, together with a growing appreciation some signaling pathways involved. However, our knowledge how growth is regulated during myelination still incomplete. The mammalian target rapamycin (mTOR) core...
Proteome and transcriptome analyses aim at comprehending the molecular profiles of brain, its cell-types subcellular compartments including myelin. Despite relevance peripheral nervous system for normal sensory motor capabilities, analogous approaches to nerves myelin have fallen behind evolving technical standards. Here we assess proteome by gel-free, label-free mass-spectrometry deep quantitative coverage. Integration with RNA-Sequencing-based developmental mRNA-abundance neuropathy...
Glia control white matter information flow The myelinated axons of the mediate rapid transmission between brain’s processing nodes. Axonal excitability and conduction speed are key determinants neural circuit function, but it is largely unknown how they regulated. Lezmy et al . examined effects adenosine on functional properties axons. They observed activity-dependent calcium rise in astrocyte processes, calcium-triggered ATP release from astrocytes, activation receptors axon initial segment...
The myelin and lymphocyte protein (MAL) is a tetraspan raft-associated proteolipid predominantly expressed by oligodendrocytes Schwann cells. We show that genetic ablation of mal resulted in cytoplasmic inclusions within compact myelin, paranodal loops are everted away from the axon, disorganized transverse bands at paranode–axon interface adult central nervous system. These structural changes were accompanied marked reduction contactin-associated protein/paranodin, neurofascin 155 (NF155),...
Ganglion cells of the myenteric plexus guinea pig were physiologically classified as to cell type using intracellular microelectrodes containing horseradish peroxidase (HRP). Interganglionic fiber tracts then stimulated in an attempt elicit slow excitatory postsynaptic potentials (EPSPs) impaled cells. The presence or absence a EPSP was noted, following which injected with HRP through recording micropipette and finally incubated tritiated 5- hydroxytryptamine ([3H]-5-HT; 0.5 microM)...
Signaling by laminins and axonal neuregulin has been implicated in regulating axon sorting myelin-forming Schwann cells. However, the signal transduction mechanisms are unknown. Focal adhesion kinase (FAK) linked to alpha6beta1 integrin ErbB receptor signaling, we show that myelination cells lacking FAK is severely impaired. Mutant could interdigitate between bundles, indicating signaling was not required for process extension. cell stimulate proliferation, suggesting amyelination caused...
SummaryPredictions that conduction velocities are sensitive to the distance between nodes of Ranvier in myelinated axons have implications for nervous system function during growth and repair [1–3]. Internodal lengths defined by Schwann cells hindlimb nerves, example, can undergo a 4-fold increase mouse development, regenerated nerves internodes uniformly short [4, 5]. Nevertheless, influence internodal length on speed has limited experimental support. Here, we examined this problem mice...
Schwann cells (SCs), ensheathing glia of the peripheral nervous system, support axonal survival and function. Abnormalities in SC metabolism affect their ability to provide this maintain axon integrity. To further interrogate metabolic influence on axon–glial interactions, we generated OGT-SCKO mice with SC-specific deletion metabolic/nutrient sensing protein O-GlcNAc transferase that mediates O-linked addition N -acetylglucosamine (GlcNAc) moieties Ser Thr residues. The develop tomaculous...