113,239 research outputs found
Neuromuscular Junction Dismantling in Amyotrophic Lateral Sclerosis
No full textNeuromuscular junction assembly and plasticity during embryonic, postnatal, and adult life are tightly regulated by the continuous cross-talk among motor nerve endings, muscle fibers, and glial cells. Altered communications among these components is thought to be responsible for the physiological age-related changes at this synapse and possibly for its destruction in pathological states. Neuromuscular junction dismantling plays a crucial role in the onset of Amyotrophic Lateral Sclerosis (ALS). ALS is characterized by the degeneration and death of motor neurons leading to skeletal muscle denervation, atrophy and, most often, death of the patient within five years from diagnosis. ALS is a non-cell autonomous disease as, besides motor neuron degeneration, glial cells, and possibly muscle fibers, play a role in its onset and progression. Here, we will review the recent literature regarding the mechanisms leading to neuromuscular junction disassembly and muscle denervation focusing on the role of the three players of this peripheral tripartite synapse
ANALYSIS OF NEUROMUSCULAR JUNCTIONS AND EFFECTS OF NANDROLONE ADMINISTRATION IN A MOUSE MODEL FOR ALS
No full textSeveral lines of evidence indicate that neuromuscular junction (NMJ) destruction and disassembly is an early phenomenon in the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. Here we analyzed by confocal and electron microscopy the NMJ structure in the diaphragm of Superoxide dismutase (SOD)1 G93A mice at symptom onset and we compared these observation with animals sacrificed at the pathological end stage. In young transgenic mice, which provide a model for familial ALS, the present findings showed marked denervation both in the diaphragm and in the gastrocnemius, which partially spares soleus muscle. At the clinical end stage even the soleus is slight denervated, but less severely than other muscles. In addition, the size of the synaptic vesicle (SV) pool was found reduced and alterations of mitochondria were observed in approximately 40% of the remaining presynaptic terminals. Treatment of SOD1 G93A mice with the anabolic steroid nandrolone during the presymptomatic stage preserved the diaphragm muscle mass and features indicative of synaptic activity, represented by the number of vesicles docked within 200 nm from the presynaptic membrane and area of acetylcholine receptor clusters. Furthermore, structural preservation of mitochondria was documented in presynaptic terminals, but innervation of diaphragm muscle fibers was only slightly increased in nandrolone-treated SOD1-mutant mice. Altogether the results point out and define fine structural alterations of diaphragm NMJs in the murine model of familial ALS at symptom onset, and indicate that nandrolone may prevent or delay structural alterations in NMJ mitochondria and stimulate presynaptic activity but does not prevent muscle denervation in the disease
Progettazione di un dispositivo paraincastro posteriore ad elevata dissipazione di energia per veicoli industriali
No full textMitochondrial Tricarboxylate and Dicarboxylate–Tricarboxylate Carriers: from animals to Plants.
No full textThe citrate carrier (CiC), characteristic of animals, and the dicarboxylate-tricarboxylate carrier (DTC), characteristic of plants and protozoa, belong to the mitochondrial carrier protein family whose members are responsible for the exchange of metabolites, cofactors and nucleotides between the cytoplasm and mitochondrial matrix. Most of the functional data on these transporters come from studies performed with the protein purified from rat, eel yeast and maize mitochondria or recombinant proteins from different sources incorporated into phospholipid vesicles (liposomes). The functional data indicate that CiC is responsible for the efflux of acetyl-CoA from the mitochondria to the cytosol in the form of citrate, the primer for fatty acid, cholesterol synthesis and histone acetylation. Like the CiC the citrate exported by DTC from the mitochondria to the cytosol in exchange for oxaloacetate can be cleaved by citrate lyase to acetyl-CoA and oxaloacetate and used for fatty acid elongation and isoprenoid synthesis. In addition to its role in fatty acid synthesis, CiC is involved in other processes such as gluconeogenesis, insulin secretion, inflammation, and cancer progression, whereas DTC is involved in production of glycerate, nitrogen assimilation, ripening of fruits, ATP synthesis and sustaining of respiratory flux in fruit cells.
This review provides an assessment of the current understanding of CiC and DTC structural and biochemical characteristics, underlying the structure–function relationship of these carriers. Furthermore a phylogenetic relationship between CiC and DTC is proposed
author-bios-SRD-19-0063.R1 – Supplemental material for The Network Structure of Police Misconduct
No full textSupplemental material, author-bios-SRD-19-0063.R1 for The Network Structure of Police Misconduct by George Wood, Daria Roithmayr and Andrew V. Papachristos in Socius</p
Sei gradi di libertà: il lavoro libero come pratica inclusiva nell’approccio Montessori
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