Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrat...Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.展开更多
In this study, we are first examining well-known approach to improve fuzzy reasoning model (FRM) by use of the genetic-based learning mechanism [1]. Later we propose our alternative way to build FRM, which has signifi...In this study, we are first examining well-known approach to improve fuzzy reasoning model (FRM) by use of the genetic-based learning mechanism [1]. Later we propose our alternative way to build FRM, which has significant precision advantages and does not require any adjustment/learning. We put together neuro-fuzzy system (NFS) to connect the set of exemplar input feature vectors (FV) with associated output label (target), both represented by their membership functions (MF). Next unknown FV would be classified by getting upper value of current output MF. After that the fuzzy truths for all MF upper values are maximized and the label of the winner is considered as the class of the input FV. We use the knowledge in the exemplar-label pairs directly with no training. It sets up automatically and then classifies all input FV from the same population as the exemplar FVs. We show that our approach statistically is almost twice as accurate, as well-known genetic-based learning mechanism FRM.展开更多
The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent...The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.展开更多
Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontane...Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neuro-trophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1–100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.展开更多
The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which...The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which is enveloped by processes of sustentacular or type II cells. Growth and neurotrophic factors have been established as signaling molecules played an important role in the development of the CB. To gain insight whether these signaling molecules are present in the adult rat CB, we examined the expression and cellular localization of some neurotrophic factors and their corresponding receptors in this organ by immunohistochemistry. The results showed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) as well as p75NTR, tyrosine kinase A receptor (TrkA), tyrosine kinase B receptor (TrkB) and GDNF family receptor alpha1 (GFRα1) in the adult CB. At the light-microscopical level, the immunoreactivity for NGF and both its low-affinity (p75) and high-affinity (TrkA) receptors was detected in the majority of glomus cells and also in a subset of sustentacular cells. BDNF and its receptors, p75 and TrkB, were observed in the glomus cells, too. Remarkably, the immunohistochemical analysis revealed that the neuron-like glomus cells, but not the glial-like sustentacular cells, expressed GDNF and GFRα1. Taken together with prior results, it can be inferred that neurotrophins may be involved in the CB cell differentiation and survival in adulthood, and may exert a potent glomic protective action as well. It is also presumable that GDNF production by glomus cells plays a pivotal role in permitting long-term viability of CB grafts, which permits their potential applicability in cell therapy as a promising tool in neurodegenerative disorders.展开更多
From November 2020 to August 2022, the diet of 12 fish species from the Samandeni reservoir was examined in order to describe the diet and the trophic level of each of them. The analysis of this vital function allows ...From November 2020 to August 2022, the diet of 12 fish species from the Samandeni reservoir was examined in order to describe the diet and the trophic level of each of them. The analysis of this vital function allows a better knowledge of the concerned ecosystem and gives opportunity for its better management. The fish were sampled with gill nets and cast net. A total of 213 stomach contents of individuals belonging to 12 species grouped in 7 families and 10 genera were analysed. Results showed low to medium vacuity coefficients. The preys were mainly composed of fish, insects, detritus, zooplankton and phytoplankton. Variability in the use of resources by individuals was evident. Thus, the 12 species were classified as fish-eating predators, granivorous, zooplanktivorous, insectivorous and filter-feeding microphages. Then, the fish trophic structure of the Samandeni reservoir was elaborated.展开更多
Background: Among patients treated for tuberculosis, 2% to 5% have a Central Nervous System (CNS) lesion, and its frequency rises to 10% in HIV-infected patients. Neuro-meningeal tuberculosis (NMT) is responsible for ...Background: Among patients treated for tuberculosis, 2% to 5% have a Central Nervous System (CNS) lesion, and its frequency rises to 10% in HIV-infected patients. Neuro-meningeal tuberculosis (NMT) is responsible for death and severe permanent neurological damage. This poor prognosis requires early diagnosis and rapid initiation of specific treatment. Unfortunately, the great clinical polymorphism and the lack of specificity of radiological and biological signs are frequently responsible for a delay in diagnosis and management. Senegal is one of the African countries where tuberculosis has remained a concern until now. And there are no studies carried out on this subject. Objective: The objective of this study was to describe the profile and outcome of Neuro-meningeal tuberculosis (NMT) cases diagnosed at the infectious diseases department (SMIT) of Fann University Hospital in Dakar, (referral service for management of tuberculosis). Methods: We carried out a retrospective, descriptive and analytical study, reviewing medical records of adults diagnosed with NMT at the SMIT of Fann Hospital from January 2015 to December 2020. Results: We collected 55 cases of NMT. The median age was 38 years [range 16 - 77 years]. The sex ratio (M/F) was 3.23. HIV patients represented 41.82% of cases. A history of tuberculosis was found in 25.5% of cases. The delay in consultation was greater than one month in 60% of patients. Headaches were the most constant reason for consultation (94.55%). Meningeal signs were present in 94.55% of patients, and consciousness disorders and intracranial hypertension were present in 63.64% and 56.36% respectively. Nerve palsy was found in 38.18%. CSF was clear in 81.64%. GeneXpert MTB/RIF in CSF was performed in 33 patients and was positive in 4 patients. Brain CT was abnormal in 72.09% of cases. Tuberculoma, hydrocephalus and meningeal contrast enhancement were the main lesions. The neuro-meningeal localization was associated with a pulmonary form in 32.7%. The lethality rate was 21.8%;higher in women (46.2% vs 14.3%;p = 0.01), in patients with a delay in consultation > 1 month (p = 0.03), and in patients who presented with consciousness disorders (p = 0.007). Conclusion: Despite the availability of the GeneXpert MTB/RIF, diagnosis of NMT remains difficult. Because of its variable clinical expression and the low sensitivity of the GeneXpert MTB/rif in the CSF, it exposes patients to serious complications. Among the factors associated with death, we found consciousness disorders, a long delay in diagnosis.展开更多
基金supported by the I+D+i project P20_00529 Consejería de Transformación Económica Industria y Conocimiento,Junta de Andalucía-FEDERsupported by project PGC2018-094654-B-100 and PID2021-124300NB-I00 funded by MCIN/AEI/FEDER“A way of making Europe”+1 种基金P.M.C.was a scholar of Ministerio de Educación y Ciencia(BES-2016-077912)in Spain and is now a“Margarita Salas”postdoctoral fellowRGH is a postdoctoral fellow from PAIDI-2019,“Talento Doctores”Junta de Andalucía in Spain,and is now a“Ramón y Cajal”fellow in Spain。
文摘Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.
文摘In this study, we are first examining well-known approach to improve fuzzy reasoning model (FRM) by use of the genetic-based learning mechanism [1]. Later we propose our alternative way to build FRM, which has significant precision advantages and does not require any adjustment/learning. We put together neuro-fuzzy system (NFS) to connect the set of exemplar input feature vectors (FV) with associated output label (target), both represented by their membership functions (MF). Next unknown FV would be classified by getting upper value of current output MF. After that the fuzzy truths for all MF upper values are maximized and the label of the winner is considered as the class of the input FV. We use the knowledge in the exemplar-label pairs directly with no training. It sets up automatically and then classifies all input FV from the same population as the exemplar FVs. We show that our approach statistically is almost twice as accurate, as well-known genetic-based learning mechanism FRM.
基金The Cell Culture Core supported by grant No.PP1498:Neural Cell Culture Core and NIH grant No.04612 Intellectual&Developmental Disabilities.The Cell,Circuits and Systems Analysis Core is supported by NICHD award No.U54HD087101-03
文摘The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.
文摘Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neuro-trophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1–100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.
文摘The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which is enveloped by processes of sustentacular or type II cells. Growth and neurotrophic factors have been established as signaling molecules played an important role in the development of the CB. To gain insight whether these signaling molecules are present in the adult rat CB, we examined the expression and cellular localization of some neurotrophic factors and their corresponding receptors in this organ by immunohistochemistry. The results showed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) as well as p75NTR, tyrosine kinase A receptor (TrkA), tyrosine kinase B receptor (TrkB) and GDNF family receptor alpha1 (GFRα1) in the adult CB. At the light-microscopical level, the immunoreactivity for NGF and both its low-affinity (p75) and high-affinity (TrkA) receptors was detected in the majority of glomus cells and also in a subset of sustentacular cells. BDNF and its receptors, p75 and TrkB, were observed in the glomus cells, too. Remarkably, the immunohistochemical analysis revealed that the neuron-like glomus cells, but not the glial-like sustentacular cells, expressed GDNF and GFRα1. Taken together with prior results, it can be inferred that neurotrophins may be involved in the CB cell differentiation and survival in adulthood, and may exert a potent glomic protective action as well. It is also presumable that GDNF production by glomus cells plays a pivotal role in permitting long-term viability of CB grafts, which permits their potential applicability in cell therapy as a promising tool in neurodegenerative disorders.
文摘From November 2020 to August 2022, the diet of 12 fish species from the Samandeni reservoir was examined in order to describe the diet and the trophic level of each of them. The analysis of this vital function allows a better knowledge of the concerned ecosystem and gives opportunity for its better management. The fish were sampled with gill nets and cast net. A total of 213 stomach contents of individuals belonging to 12 species grouped in 7 families and 10 genera were analysed. Results showed low to medium vacuity coefficients. The preys were mainly composed of fish, insects, detritus, zooplankton and phytoplankton. Variability in the use of resources by individuals was evident. Thus, the 12 species were classified as fish-eating predators, granivorous, zooplanktivorous, insectivorous and filter-feeding microphages. Then, the fish trophic structure of the Samandeni reservoir was elaborated.
文摘Background: Among patients treated for tuberculosis, 2% to 5% have a Central Nervous System (CNS) lesion, and its frequency rises to 10% in HIV-infected patients. Neuro-meningeal tuberculosis (NMT) is responsible for death and severe permanent neurological damage. This poor prognosis requires early diagnosis and rapid initiation of specific treatment. Unfortunately, the great clinical polymorphism and the lack of specificity of radiological and biological signs are frequently responsible for a delay in diagnosis and management. Senegal is one of the African countries where tuberculosis has remained a concern until now. And there are no studies carried out on this subject. Objective: The objective of this study was to describe the profile and outcome of Neuro-meningeal tuberculosis (NMT) cases diagnosed at the infectious diseases department (SMIT) of Fann University Hospital in Dakar, (referral service for management of tuberculosis). Methods: We carried out a retrospective, descriptive and analytical study, reviewing medical records of adults diagnosed with NMT at the SMIT of Fann Hospital from January 2015 to December 2020. Results: We collected 55 cases of NMT. The median age was 38 years [range 16 - 77 years]. The sex ratio (M/F) was 3.23. HIV patients represented 41.82% of cases. A history of tuberculosis was found in 25.5% of cases. The delay in consultation was greater than one month in 60% of patients. Headaches were the most constant reason for consultation (94.55%). Meningeal signs were present in 94.55% of patients, and consciousness disorders and intracranial hypertension were present in 63.64% and 56.36% respectively. Nerve palsy was found in 38.18%. CSF was clear in 81.64%. GeneXpert MTB/RIF in CSF was performed in 33 patients and was positive in 4 patients. Brain CT was abnormal in 72.09% of cases. Tuberculoma, hydrocephalus and meningeal contrast enhancement were the main lesions. The neuro-meningeal localization was associated with a pulmonary form in 32.7%. The lethality rate was 21.8%;higher in women (46.2% vs 14.3%;p = 0.01), in patients with a delay in consultation > 1 month (p = 0.03), and in patients who presented with consciousness disorders (p = 0.007). Conclusion: Despite the availability of the GeneXpert MTB/RIF, diagnosis of NMT remains difficult. Because of its variable clinical expression and the low sensitivity of the GeneXpert MTB/rif in the CSF, it exposes patients to serious complications. Among the factors associated with death, we found consciousness disorders, a long delay in diagnosis.
文摘为了解中东大西洋渔业产区渔获物的资源状况,根据世界粮农组织(FAO)提供的该海域1950—2019年的渔获量数据,结合渔获种类的平均营养级(mean trophic level,MTL)信息,运用统计学方法分析70年间渔获物平均营养级和营养级平衡指数(fishing in balance,FiB)的变动规律,以掌握该海域渔业资源的可持续利用情况。结果显示,MTL大致可分为4个阶段,1950—1956年,MTL指数在3.20左右,无明显变化;1957—1963年,MTL指数迅速上升至3.44;1964—1996年,MTL在波动中趋于下降,历史最高值(3.54)出现在1985年;1997—2019年,MTL稳定在较高水平,其中2018年为该阶段最低点3.35。FiB指数整体呈上升趋势,1950—1956年,FiB指数呈小幅波动增加;1957—1974年,FiB指数显著上升;1975—1996年,FiB指数呈平稳波动状态;1997—2019年,FiB指数整体呈小幅增长趋势。结果表明,中东大西洋海洋生态系统相对稳定,但潜在的渔业资源量越来越少,开发潜力有限。
