During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el...During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal o展开更多
Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the m...Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.展开更多
We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg...We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg pain. Computed tomography (CT) showed an intracanalar mass with calcification or ossification, which most likely originated from the vertebral body at the L1/2 level epidural space. On a T1-weighted gadolinium magnetic resonance image, the capsule of the mass was enhanced and not only the content of the mass but also that of the L2 vertebral body were partially and slightly enhanced. The final pathological diagnosis was disc herniation with end-plate fracture and secondary ossification. A combination of these pathological conditions as accompanied by both end-plate fractures and extensive secondary ossifications has not been previously reported. This rare pathological condition needs to be recognized as a differential diagnosis.展开更多
Based on full scale model of 1-beam and end-plate welding assembly with medium plate, welding temperature field and residual stress were simulated, infrared thermometers were employed to measure the real-time temperat...Based on full scale model of 1-beam and end-plate welding assembly with medium plate, welding temperature field and residual stress were simulated, infrared thermometers were employed to measure the real-time temperature Jbr verification purposes. Results show that the measured thermal cycle curves match well with the simulation result. Simulation results of welding residual stress indicate that the values of longitudinal and transverse stress on the upper surface of the plate are higher than the normal stress; higher tensile stresses exist at the end of the web weld toes and in the central area of the flange weld toes. The dangerous zones are located at the central areas of weld toes of the flange welds and near weld toes of the web welds.展开更多
基金supported by Catalan Government,Nos.2014SGR344(to JT),2017SGR704(to JT),2021SGR01214(to MAL)MCIN/AEI/10.13039/501100011033/by“ERDF A way of making Europe,”Nos.SAF2015-67143(to JT),PID2019-106332GB-I00(to JT and MAL)and PID2022-141252NB-I00(to MAL).
文摘During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal o
文摘Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.
文摘We report a unique case of lumbar disc herniation, in particular, with end-plate and surrounded by extensive ossification, mimicking a tumor with calcification. A 69-year-old female suffered from right buttock and leg pain. Computed tomography (CT) showed an intracanalar mass with calcification or ossification, which most likely originated from the vertebral body at the L1/2 level epidural space. On a T1-weighted gadolinium magnetic resonance image, the capsule of the mass was enhanced and not only the content of the mass but also that of the L2 vertebral body were partially and slightly enhanced. The final pathological diagnosis was disc herniation with end-plate fracture and secondary ossification. A combination of these pathological conditions as accompanied by both end-plate fractures and extensive secondary ossifications has not been previously reported. This rare pathological condition needs to be recognized as a differential diagnosis.
基金This research was supported by the National Natural Science Foundation of China （51171093）.
文摘Based on full scale model of 1-beam and end-plate welding assembly with medium plate, welding temperature field and residual stress were simulated, infrared thermometers were employed to measure the real-time temperature Jbr verification purposes. Results show that the measured thermal cycle curves match well with the simulation result. Simulation results of welding residual stress indicate that the values of longitudinal and transverse stress on the upper surface of the plate are higher than the normal stress; higher tensile stresses exist at the end of the web weld toes and in the central area of the flange weld toes. The dangerous zones are located at the central areas of weld toes of the flange welds and near weld toes of the web welds.
