Neuromuscular effects of G93A-SOD1 expression in zebrafish

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal disorder involving the degeneration and loss of motor neurons. The mechanisms of motor neuron loss in ALS are unknown and there are no effective treatments. Defects in the distal axon and at the neuromuscular junction are early events in the disease course, and zebrafish provide a promising in vivo system to examine cellular mechanisms and treatments for these events in ALS pathogenesis. Results We demonstrate that transient genetic manipulation of zebrafish to express G93A-SOD1, a mutation associated with familial ALS, results in early defects in motor neuron outgrowth and axonal branching. This is consistent with previous reports on motor neuron axonal defects associated with familial ALS genes following knockdown or mutant protein overexpression. We also demonstrate that upregulation of growth factor signaling is capable of rescuing these early defects, validating the potential of the model for therapeutic discovery. We generated stable transgenic zebrafish lines expressing G93A-SOD1 to further characterize the consequences of G93A-SOD1 expression on neuromuscular pathology and disease progression. Behavioral monitoring reveals evidence of motor dysfunction and decreased activity in transgenic ALS zebrafish. Examination of neuromuscular and neuronal pathology throughout the disease course reveals a loss of neuromuscular junctions and alterations in motor neuron innervations patterns with disease progression. Finally, motor neuron cell loss is evident later in the disease. Conclusions This sequence of events reflects the stepwise mechanisms of degeneration in ALS, and provides a novel model for mechanistic discovery and therapeutic development for neuromuscular degeneration in ALS.http://deepblue.lib.umich.edu/bitstream/2027.42/112892/1/13024_2012_Article_367.pd

In situ monitoring of isophorone diisocyanate-based flexible polyurethane foams formation

Publisher Copyright: © The Author(s) 2016.Novel isophorone diisocyanate-based flexible polyurethane foams were prepared by the one-step method in a computerized foam qualification system (FOAMAT). The experimental conditions to obtain this type of foams, in relation to the nature and concentration of catalysts as well as the reaction temperature, were established as no data were available in scientific literature. The chemical reactions occurring during the foam generation process were monitored in situ by attenuated total reflectance-FTIR spectroscopy. The kinetics of the foam generation was fitted to an nth order model and the data showed that the foaming process adjusted to a first-order kinetics. The physical changes as pressure, foam height, and dielectric polarization were monitored by the FOAM software (FOAMAT). According to these parameters, the foaming process was divided into four steps: bubble growth, bubble packing, cell opening, and final curing.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors thank the Basque Government (Grupo consolidado, IT 61-8-13) and the University of the Basque Country (UFI 11/56) for the funding received to develop this work.Peer reviewe

Ammonium polyphosphate-melamine synergies in thermal degradation and smoke toxicity of flexible polyurethane foams

Publisher Copyright: © 2023Polyurethane (PUR) foams can lead to fatal fires in the presence of an ignition and oxygen source. Obviously, the problem is not the mere loss of PUR foams properties but essentially, the smoke and toxic gases which are the main factors responsible for fire hazards. This paper reports on the main approaches taken to improve the smoke evolution and toxicity of isophorone diisocyanate (IPDI) based PUR foams which are the incorporation of ammonium polyphosphate (APP), melamine (M) and its combinations as additive flame retardants (FRs). In order to better understand the fire behavior, the influence of incorporated FR on the thermal degradation mechanism was also analyzed by means of thermogravimetry coupled to infrared spectroscopy (TGA-FTIR). In addition, foams were characterized in terms of smoke evolution and toxicity of released gases both asphyxiant and irritant using a smoke density chamber coupled to infrared spectroscopy (NBS-FTIR). Data showed that the mixture of APP and M in different amounts reduced the smoke generation and the concentration of harmful gases, underlying a synergetic effect for the combination of both flame-retardants.The authors thank the Basque Government ( IT1667-22 , IT1503-22 , PIBA20/16 ) and the University of the Basque Country ( GIU19/077 ) for the funding received to develop this work. I. E. also thanks the Basque Government for the PhD scholarship and Iñaki Goenaga Foundation.Peer reviewe

Neuromuscular effects of G93A-SOD1 expression in zebrafish

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder involving the degeneration and loss of motor neurons. The mechanisms of motor neuron loss in ALS are unknown and there are no effective treatments. Defects in the distal axon and at the neuromuscular junction are early events in the disease course, and zebrafish provide a promising in vivo system to examine cellular mechanisms and treatments for these events in ALS pathogenesis. RESULTS: We demonstrate that transient genetic manipulation of zebrafish to express G93A-SOD1, a mutation associated with familial ALS, results in early defects in motor neuron outgrowth and axonal branching. This is consistent with previous reports on motor neuron axonal defects associated with familial ALS genes following knockdown or mutant protein overexpression. We also demonstrate that upregulation of growth factor signaling is capable of rescuing these early defects, validating the potential of the model for therapeutic discovery. We generated stable transgenic zebrafish lines expressing G93A-SOD1 to further characterize the consequences of G93A-SOD1 expression on neuromuscular pathology and disease progression. Behavioral monitoring reveals evidence of motor dysfunction and decreased activity in transgenic ALS zebrafish. Examination of neuromuscular and neuronal pathology throughout the disease course reveals a loss of neuromuscular junctions and alterations in motor neuron innervations patterns with disease progression. Finally, motor neuron cell loss is evident later in the disease. CONCLUSIONS: This sequence of events reflects the stepwise mechanisms of degeneration in ALS, and provides a novel model for mechanistic discovery and therapeutic development for neuromuscular degeneration in ALS

Neuromuscular effects of G93A-SOD1 expression in zebrafish

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal disorder involving the degeneration and loss of motor neurons. The mechanisms of motor neuron loss in ALS are unknown and there are no effective treatments. Defects in the distal axon and at the neuromuscular junction are early events in the disease course, and zebrafish provide a promising in vivo system to examine cellular mechanisms and treatments for these events in ALS pathogenesis. Results We demonstrate that transient genetic manipulation of zebrafish to express G93A-SOD1, a mutation associated with familial ALS, results in early defects in motor neuron outgrowth and axonal branching. This is consistent with previous reports on motor neuron axonal defects associated with familial ALS genes following knockdown or mutant protein overexpression. We also demonstrate that upregulation of growth factor signaling is capable of rescuing these early defects, validating the potential of the model for therapeutic discovery. We generated stable transgenic zebrafish lines expressing G93A-SOD1 to further characterize the consequences of G93A-SOD1 expression on neuromuscular pathology and disease progression. Behavioral monitoring reveals evidence of motor dysfunction and decreased activity in transgenic ALS zebrafish. Examination of neuromuscular and neuronal pathology throughout the disease course reveals a loss of neuromuscular junctions and alterations in motor neuron innervations patterns with disease progression. Finally, motor neuron cell loss is evident later in the disease. Conclusions This sequence of events reflects the stepwise mechanisms of degeneration in ALS, and provides a novel model for mechanistic discovery and therapeutic development for neuromuscular degeneration in ALS.</p

Autonomous Learning Mediated by Digital Technology Processes in Higher Education: A Systematic Review

The concept of autonomous learning has been resignified in recent years as a result of the expansion of the different types of study. Online education in higher education institutions has become an effective option to increase and diversify opportunities for access and learning, however, high rates of dropout, reprisal and low averages still persist. academic performance. Recent research shows that the problem is accentuated because most students have difficulty self-regulating their own learning process autonomously. From this perspective, the purpose of the study was to examine and analyze, through a systematic review of the literature, on autonomous/self-regulated learning, theoretical models and determine which variables influence a learning process mediated by technology processes in the higher education. The findings indicate that: (1) autonomous learning is a synonym of self-regulation; (2) Pintrich’s self-regulatory model is the most used in digital contexts; and (3) the self-regulatory variables identified are wide and varied. © Springer Nature Switzerland AG 2020