Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibi...Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investiga展开更多
为了探究σB因子对单增李斯特菌(LM)的生长影响,比较了LM-WaX12及其sigma B缺失突变株在不同pH值下生长动力学的差异。作者运用重叠延伸PCR(SOE-PCR)和同源重组的方法构建缺失SigB基因的LM突变株WaX12-△sigB;利用sigB外围引物扩增...为了探究σB因子对单增李斯特菌(LM)的生长影响,比较了LM-WaX12及其sigma B缺失突变株在不同pH值下生长动力学的差异。作者运用重叠延伸PCR(SOE-PCR)和同源重组的方法构建缺失SigB基因的LM突变株WaX12-△sigB;利用sigB外围引物扩增其两侧片段鉴定突变株,并且通过修正的Logistic模型拟合两个菌株在不同酸碱度下(p H 59)的生长曲线,分析各生长参数之间的差异性。结果表明,单增李斯特菌sigB缺失突变株构建成功;WaX12-△sigB和WaX12在p H 5的环境下最大比生长速率μmax、延滞期λ与最大菌浓MPD-OD均存在显著性差异(P〈0.05),而在中性和碱性环境下二者无明显差异。展开更多
基金a Ph D fellowship by FCT-Fundacao para a Ciência Tecnologia (SFRH/BD/135868/2018)(to SSC)。
文摘Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investiga
文摘为了探究σB因子对单增李斯特菌(LM)的生长影响,比较了LM-WaX12及其sigma B缺失突变株在不同pH值下生长动力学的差异。作者运用重叠延伸PCR(SOE-PCR)和同源重组的方法构建缺失SigB基因的LM突变株WaX12-△sigB;利用sigB外围引物扩增其两侧片段鉴定突变株,并且通过修正的Logistic模型拟合两个菌株在不同酸碱度下(p H 59)的生长曲线,分析各生长参数之间的差异性。结果表明,单增李斯特菌sigB缺失突变株构建成功;WaX12-△sigB和WaX12在p H 5的环境下最大比生长速率μmax、延滞期λ与最大菌浓MPD-OD均存在显著性差异(P〈0.05),而在中性和碱性环境下二者无明显差异。