Reactive astrocytes contribute to glial scarring by rapid proliferation and up-regulation of glial fibrillary acidic protein (GFAP) expression and production of chondroitin sulfate proteoglycans (CSPGs). CSPGs play a ...Reactive astrocytes contribute to glial scarring by rapid proliferation and up-regulation of glial fibrillary acidic protein (GFAP) expression and production of chondroitin sulfate proteoglycans (CSPGs). CSPGs play a crucial role in formation of the glial scar, which takes over the lesion site following spinal cord injury (SCI). This process corresponds to the inflammatory response of macrophages, which polarize toward a dominant pro-inflammatory M1 phenotype following SCI. The M1 phenotype is known to release various cytotoxic compounds that exacerbate the glial scar, which in turn impedes tissue regeneration. Recent studies have shown that anti-inflammatory M2 macrophages play a role in allowing neurite extensions to occur, even across inhibitory substrates, and can lessen the degree of secondary damage. Based on earlier results demonstrating that keratin biomaterials may polarize macrophages toward an anti-inflammatory M2 phenotype, we test the hypothesis that these polarized macrophages will have the potential to indirectly effect astrogliosis. Using an in vitro model of reactive astrogliosis, macrophage-conditioned media from cells that have been cultured with soluble keratin for 24 hours or 7 days appears to decrease reactivity and associates CSPG production. These results are statistically similar to the control M2 macrophage conditioned media. A comparable collagen-conditioned macrophage media does not resolve astrocyte reactivity, while control M1 macrophage conditioned media results in an increase in GFAP expression. These data suggest keratin-derived macrophages are more functionally similar to M2 macrophages and that keratin treatment may aid in limiting secondary inflammatory-mediated damage.展开更多
Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty p...Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty proteases with potent endopeptidase activity.They are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal function.Although cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal plasticity.We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease.Importantly,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury.It is well established that normal cathepsin activity is integral to the function of lysosomes.Without normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy.Furthermore,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity.This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.展开更多
Stroke is a leading cause of death and disability in adults worldwide. For decades, the primary approach and goal of therapy for stroke has focused on neuroprotection, namely treating the injured tissue, with interven...Stroke is a leading cause of death and disability in adults worldwide. For decades, the primary approach and goal of therapy for stroke has focused on neuroprotection, namely treating the injured tissue, with interventions designed to reduce the volume of cerebral infarction. Enormous effort in the laboratory has been devoted to the development of neuroprotective agents in an attempt to salvage ischemic neurons in the brain from irreversible injury; however, all these efforts have failed to demonstrate efficacy in clinical trials of stroke. In order to treat stroke, we have to re-con- ceptualize and redefine our therapeutic targets. Acute neu- roprotective treatments for stroke fight a temporal battle of salvaging cerebral tissue before the onset of death, as well as a physiological impediment of delivery of therapy to tissue which has inadequate blood flow.展开更多
Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as ...Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,展开更多
The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatial...The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatially regulated and is a dynamic ＂living＂ entity that is reshaped and redesigned on a continuous basis in response to changing needs. Some modifications are adaptive and some are maladaptive. It is the maladaptive responses that pose a significant threat to successful axonal regeneration and/or sprouting following traumatic and spinal cord injuries, and has been the focus of a myriad of research laboratories for many years. This review focuses largely on the extracellular matrix component, chondroitin sulfate proteoglycans, with certain comparisons to heparan sulfate proteoglycans, which tend to serve opposite functions in the central nervous system. Although about equally as well characterized as some of the other proteoglycans such as hyaluronan and dermatan sulfate proteoglycan, chondroitin sulfate proteoglycans are the most widely researched and discussed proteoglycans in the field of axonal injury and regeneration. Four laboratories discuss various aspects of chondroitin sulfate proteoglycans and proteoglycans in general with respect to their structure and function （Beller and Snow）, the recent discovery of specific chondroitin sulfate proteoglycan receptors and what this may mean the field （Shen）, extracellular for increased advancements in matrix degradation by matrix metalloproteinases, which sculpt and resculpt to provide support for outgrowth, synapse formation, and synapse stability （Phillips et al.）, and the perilesion microenvironment with respect to immune system function in response to proteoglycans and central nervous system injuries （Jakeman et al.）.展开更多
This study aimed to evaluate the effect of natural weathering on some surface characteristics and mechanical properties of Styrax wood treated with mixtures of 1.0%,2.0%,or 4.0%rosin sizing agent and 3%copper sulfate....This study aimed to evaluate the effect of natural weathering on some surface characteristics and mechanical properties of Styrax wood treated with mixtures of 1.0%,2.0%,or 4.0%rosin sizing agent and 3%copper sulfate.Wood samples after treatment were exposed to outdoor conditions for one year and changes in color,glossiness,weight loss,compression strength parallel to grain(CSPG),modulus of rupture(MOR),and modulus of elasticity(MOE)were investigated after 6 and 12-month of natural weathering.The results showed that rosin-copper treatment could improve color stability and gloss of samples after weathering.Mass losses of all rosin-copper treated samples after 12 months of exposure were negligible compared with the untreated control samples.In addition,rosin-copper treatment enhanced the CSPG compared to untreated controls,but slightly decreased the MOR and MOE of Styrax wood before weathering.Natural weathering factors induced a reduction for all strength properties,however,the decrease rate for strength properties of rosin-copper treated samples was negligible compared with the untreated control samples after 12-month natural weathering exposure.The FTIR and SEM-EDX confirmed that the use of the rosin-copper formulations to impregnate wood could decrease the hazard of the copper preservative leaching into the environment,while also enhancing more resistance against weathering factors and other biotic factors.展开更多
Accurately measuring precipitation is integral for understanding water cycle processes and assessing climate change in the Qinghai–Tibet Plateau(QTP).The Geonor T-200B weighing precipitation gauge with a single Alter...Accurately measuring precipitation is integral for understanding water cycle processes and assessing climate change in the Qinghai–Tibet Plateau(QTP).The Geonor T-200B weighing precipitation gauge with a single Alter shield(Geonor)and the Chinese standard precipitation gauge(CSPG)are widely used for measuring precipitation in the QTP.However,their measurements need to be adjusted for wetting loss,evaporation loss and windinduced undercatch.Four existing transfer functions for adjusting the Geonor-recorded and three transfer functions for adjusting the CSPG-recorded precipitation at hourly,daily or event scale has been proposed based on the precipitation intercomparison experiments conducted at a single site in different regions.Two latest transfer functions for the Geonor(which are referred to as K2017a and K2017b)at the half-hour time scale based on the precipitation intercomparison experiments at multiple stations in the northern hemisphere were provided in the World Meteorological Organization Solid Precipitation Intercomparison Experiment.However,the applicability of these transfer functions in the QTP has not been evaluated.Therefore,the current study carried out a precipitation measurement intercomparison experiment between August 2018 and September 2020 at a site in Beiluhe in central QTP.The performance of these transfer functions at this site was also evaluated on the basis of mean bias(MB),root mean squared error(RMSE)and relative total catch(RTC).The results are as follows:First,the unadjusted RTC values of the Geonor for rain,mixed(snow mixed with rain),snow and hail are 92.06%,85.35%,64.11% and 91.82%,respectively,and the unadjusted RTC values of the CSPG for the same precipitation types are 92.59%,81.32%,46.43% and 95.56%,respectively.Second,K2017a has the most accurate adjustment results for the Geonor-recorded snow and mixed precipitation at the half-hour time scale,and the post-adjustment RTC values increased to 98.25% and 98.23%,respectively.M2007e,an event-based transfer function,was found to have the most accurate adjustment results for the Geonorrecorded snow precipitation at the event scale,and the post-adjustment RTC value increased to 96.36%.Third,the existing transfer functions for CSPG underestimate snowfall,while overestimating rainfall.Fourth,hail is a significant precipitation type in central QTP.The catch efficiency of hail precipitation and the temperature when hail precipitation occurs are close to those of rain;moreover,the transfer functions for rain are suitable for hail as well.展开更多
文摘Reactive astrocytes contribute to glial scarring by rapid proliferation and up-regulation of glial fibrillary acidic protein (GFAP) expression and production of chondroitin sulfate proteoglycans (CSPGs). CSPGs play a crucial role in formation of the glial scar, which takes over the lesion site following spinal cord injury (SCI). This process corresponds to the inflammatory response of macrophages, which polarize toward a dominant pro-inflammatory M1 phenotype following SCI. The M1 phenotype is known to release various cytotoxic compounds that exacerbate the glial scar, which in turn impedes tissue regeneration. Recent studies have shown that anti-inflammatory M2 macrophages play a role in allowing neurite extensions to occur, even across inhibitory substrates, and can lessen the degree of secondary damage. Based on earlier results demonstrating that keratin biomaterials may polarize macrophages toward an anti-inflammatory M2 phenotype, we test the hypothesis that these polarized macrophages will have the potential to indirectly effect astrogliosis. Using an in vitro model of reactive astrogliosis, macrophage-conditioned media from cells that have been cultured with soluble keratin for 24 hours or 7 days appears to decrease reactivity and associates CSPG production. These results are statistically similar to the control M2 macrophage conditioned media. A comparable collagen-conditioned macrophage media does not resolve astrocyte reactivity, while control M1 macrophage conditioned media results in an increase in GFAP expression. These data suggest keratin-derived macrophages are more functionally similar to M2 macrophages and that keratin treatment may aid in limiting secondary inflammatory-mediated damage.
基金JS was funded by NINDS(NS25713)Brumagin-Nelson Fund+1 种基金Kaneko Family Fundthe Hong Kong Spinal Cord Injury Fund.
文摘Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty proteases with potent endopeptidase activity.They are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal function.Although cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal plasticity.We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease.Importantly,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury.It is well established that normal cathepsin activity is integral to the function of lysosomes.Without normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy.Furthermore,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity.This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.
基金supported by National Institute of Neurological Disorders and Stroke(NINDS)of the National Institutes of Health under award number R01NS066041(ZL),R01NS081189(HX) and R01AG037506(MC)
文摘Stroke is a leading cause of death and disability in adults worldwide. For decades, the primary approach and goal of therapy for stroke has focused on neuroprotection, namely treating the injured tissue, with interventions designed to reduce the volume of cerebral infarction. Enormous effort in the laboratory has been devoted to the development of neuroprotective agents in an attempt to salvage ischemic neurons in the brain from irreversible injury; however, all these efforts have failed to demonstrate efficacy in clinical trials of stroke. In order to treat stroke, we have to re-con- ceptualize and redefine our therapeutic targets. Acute neu- roprotective treatments for stroke fight a temporal battle of salvaging cerebral tissue before the onset of death, as well as a physiological impediment of delivery of therapy to tissue which has inadequate blood flow.
基金NIH PO1 NS055976,Craig H.Neilsen Foundation,and Shriner’s Hospital for Children
文摘Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,
文摘The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatially regulated and is a dynamic ＂living＂ entity that is reshaped and redesigned on a continuous basis in response to changing needs. Some modifications are adaptive and some are maladaptive. It is the maladaptive responses that pose a significant threat to successful axonal regeneration and/or sprouting following traumatic and spinal cord injuries, and has been the focus of a myriad of research laboratories for many years. This review focuses largely on the extracellular matrix component, chondroitin sulfate proteoglycans, with certain comparisons to heparan sulfate proteoglycans, which tend to serve opposite functions in the central nervous system. Although about equally as well characterized as some of the other proteoglycans such as hyaluronan and dermatan sulfate proteoglycan, chondroitin sulfate proteoglycans are the most widely researched and discussed proteoglycans in the field of axonal injury and regeneration. Four laboratories discuss various aspects of chondroitin sulfate proteoglycans and proteoglycans in general with respect to their structure and function （Beller and Snow）, the recent discovery of specific chondroitin sulfate proteoglycan receptors and what this may mean the field （Shen）, extracellular for increased advancements in matrix degradation by matrix metalloproteinases, which sculpt and resculpt to provide support for outgrowth, synapse formation, and synapse stability （Phillips et al.）, and the perilesion microenvironment with respect to immune system function in response to proteoglycans and central nervous system injuries （Jakeman et al.）.
基金the support of the Vietnam National Foundation for Science and Technology Development(NAFOSTED)[Grant No.106.99-2018.16].
文摘This study aimed to evaluate the effect of natural weathering on some surface characteristics and mechanical properties of Styrax wood treated with mixtures of 1.0%,2.0%,or 4.0%rosin sizing agent and 3%copper sulfate.Wood samples after treatment were exposed to outdoor conditions for one year and changes in color,glossiness,weight loss,compression strength parallel to grain(CSPG),modulus of rupture(MOR),and modulus of elasticity(MOE)were investigated after 6 and 12-month of natural weathering.The results showed that rosin-copper treatment could improve color stability and gloss of samples after weathering.Mass losses of all rosin-copper treated samples after 12 months of exposure were negligible compared with the untreated control samples.In addition,rosin-copper treatment enhanced the CSPG compared to untreated controls,but slightly decreased the MOR and MOE of Styrax wood before weathering.Natural weathering factors induced a reduction for all strength properties,however,the decrease rate for strength properties of rosin-copper treated samples was negligible compared with the untreated control samples after 12-month natural weathering exposure.The FTIR and SEM-EDX confirmed that the use of the rosin-copper formulations to impregnate wood could decrease the hazard of the copper preservative leaching into the environment,while also enhancing more resistance against weathering factors and other biotic factors.
基金supported primarily by the National Natural Sciences Foundation of China(42171467,42001060 and 41705139)Natural Science Foundation of Qinghai Province(2021-ZJ947Q)。
文摘Accurately measuring precipitation is integral for understanding water cycle processes and assessing climate change in the Qinghai–Tibet Plateau(QTP).The Geonor T-200B weighing precipitation gauge with a single Alter shield(Geonor)and the Chinese standard precipitation gauge(CSPG)are widely used for measuring precipitation in the QTP.However,their measurements need to be adjusted for wetting loss,evaporation loss and windinduced undercatch.Four existing transfer functions for adjusting the Geonor-recorded and three transfer functions for adjusting the CSPG-recorded precipitation at hourly,daily or event scale has been proposed based on the precipitation intercomparison experiments conducted at a single site in different regions.Two latest transfer functions for the Geonor(which are referred to as K2017a and K2017b)at the half-hour time scale based on the precipitation intercomparison experiments at multiple stations in the northern hemisphere were provided in the World Meteorological Organization Solid Precipitation Intercomparison Experiment.However,the applicability of these transfer functions in the QTP has not been evaluated.Therefore,the current study carried out a precipitation measurement intercomparison experiment between August 2018 and September 2020 at a site in Beiluhe in central QTP.The performance of these transfer functions at this site was also evaluated on the basis of mean bias(MB),root mean squared error(RMSE)and relative total catch(RTC).The results are as follows:First,the unadjusted RTC values of the Geonor for rain,mixed(snow mixed with rain),snow and hail are 92.06%,85.35%,64.11% and 91.82%,respectively,and the unadjusted RTC values of the CSPG for the same precipitation types are 92.59%,81.32%,46.43% and 95.56%,respectively.Second,K2017a has the most accurate adjustment results for the Geonor-recorded snow and mixed precipitation at the half-hour time scale,and the post-adjustment RTC values increased to 98.25% and 98.23%,respectively.M2007e,an event-based transfer function,was found to have the most accurate adjustment results for the Geonorrecorded snow precipitation at the event scale,and the post-adjustment RTC value increased to 96.36%.Third,the existing transfer functions for CSPG underestimate snowfall,while overestimating rainfall.Fourth,hail is a significant precipitation type in central QTP.The catch efficiency of hail precipitation and the temperature when hail precipitation occurs are close to those of rain;moreover,the transfer functions for rain are suitable for hail as well.
