Extensive iron deposition has been observed in the midbrain substantia nigra (SN) of Parkinson's disease (PD) patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study ...Extensive iron deposition has been observed in the midbrain substantia nigra (SN) of Parkinson's disease (PD) patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study investigated the relationship between dopaminergic neuronal damage, iron content changes, and divalent metal transporter 1 (DMT1) in the midbrain SN of PD rats to explore the relationship between time of iron deposition and DMT1 expression. Frozen midbrain SN sections from model rats were stained with Perls' iron. Results showed massive loss of tyrosine hydroxylase (TH)-positive cells in the SN and increased DMT1 expression in model group rats. No obvious iron deposition was observed in the SN during early stages after damage, but significant iron deposition was detected at 8 weeks post-injury. Results demonstrate that the loss of TH-positive cells in the SN appeared simultaneously with increased DMT1 expression. Extensive iron deposition occurred at 8 weeks post injury, which could be regarded as an early time window of iron deposition.展开更多
Iron plays a key role in Parkinson's disease (PD). Increased iron content of the substantia nigra (SN) has been found in PD patients, and divalent metal transporter 1 (DMT1) has been shown to be up-regulated in...Iron plays a key role in Parkinson's disease (PD). Increased iron content of the substantia nigra (SN) has been found in PD patients, and divalent metal transporter 1 (DMT1) has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine (6-OHDA)-induced PD rats, DMT1 with the iron responsive element (IRE, DMTI+IRE), but not DMT1 without IRE (DMTI-IRE), was up- regulated, suggesting that increased DMTI+IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMTl+IRE-over-expressing MES23.5 cells. In 6-OHDA-treated MES23.5 cells, increased iron regulatory protein (IRP) 1 and IRP2 expression was observed, while silencing of IRPs dramatically diminished 6-OHDA-indueed DMTI+IRE up-regulation. Pre- treatment with N-acetyl-L-cysteine fully suppressed IRPs up-regulation by inhibition of 6-OHDA-indueed oxidative stress. Increased DMTI+IRE expression resulted in increased iron influx by MES23.5 cells. Our data provide direct evidence that DMTI+IRE up-regulation can account for IRE/IRP-dependent 6-OHDA-induced iron accumulation initiated by 6-OHDA-induced intracellular oxidative stress and that increased levels of intracellular iron result in ag- gravated oxidative stress. The results of this study provide novel evidence supporting the use of anti-oxidants in the treatment of PD, with the goal of inhibiting iron accumulation by regulation of DMT1 expression.展开更多
AIM:To describe the variation that divalent metaltransporter 1(DMT1)shows in patients after Rouxen-Y gastric bypass(RYGB)surgery.METHODS:Prospective and analytical study of DMT1level at the brush border of proximal je...AIM:To describe the variation that divalent metaltransporter 1(DMT1)shows in patients after Rouxen-Y gastric bypass(RYGB)surgery.METHODS:Prospective and analytical study of DMT1level at the brush border of proximal jejunum in patients having undergone RYGB surgery.The mucosa of proximal jejunum forming the gastrojejunal anastomosis was biopsied during surgery and after 6 mo later with an endoscopic biopsy.All the patients received precise instructions regarding feeding and nutritional supplementation.Both samples were processed at the same time by immunohistochemistry and western blot.Samples were analysed by a pathologist.For statistical analysis,theχ2 and Wilcoxon tests were used.RESULTS:Sixteen patients were recruited,13 of whom completed the study.Twelve were women.Average age and body mass index(BMI)were 44.1 and 40.4,respectively.Both body weight and BMI decreased significantly during the study period,with an average percent excess weight loss(%EWL)of 60%±13.3%and an average percent excess BMI loss(%EBMIL)of 79.6%±21.6%.Only two patients presented with mild anaemia6 mo after surgery,but their ferritin levels stayed within normal ranges.Staining for DMT1 showed a significant increase in the cytoplasm of enterocytes located at the tips of the villi(χ2=6.03;P=0.049).Nevertheless,the total quantity of DMT1 decreased significantly(Z=2.04;P=0.04).Associated with these results,we observed a significant increase in goblet cells in the villi 6mo postoperatively(Z=-2.47;P=0.013).CONCLUSION:Six months after RYGB surgery,patients exhibit an increase in DMT1 expression in the enterocytes of the tips of the villi at the proximal jejunum.展开更多
There is no enough information about metal transport parameters in residual soil. These soils are generally structured and still there is no answer to what happens with the contaminant transport parameters when an aci...There is no enough information about metal transport parameters in residual soil. These soils are generally structured and still there is no answer to what happens with the contaminant transport parameters when an acid solution with metal percolates this material with different structure. The objective of this study was to determine the contaminant transport parameters for Cd, Ni, Cu and Zn metals in an acid multispecies solution to a residual soil from south Brazil with an undisturbed and remolded structure. Column tests were carried out to determine the kd, Rd, Dh transport parameters. It was possible conclude that the magnitude of the kd, Rd and Dh parameter did not vary significantly with the soil structure.展开更多
The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
We study a particular combination of charge and heat currents, which is decoupled with the heat current.The "heat-decoupled"(HD) current can be transported by diffusion at long distances, when the thermoelec...We study a particular combination of charge and heat currents, which is decoupled with the heat current.The "heat-decoupled"(HD) current can be transported by diffusion at long distances, when the thermoelectric effect is small, large, or balanced. Using holographic models with momentum relaxation, we illustrate that the different thermoelectric effects correspond to the high temperatures and strong disorder, low temperatures, or special critical index. Meanwhile, the Einstein-like relation and the diffusion/chaos relation may be emergent. Assuming that the existence and features of HD modes appear in strange metals, we can predict that when the thermoelectric effect is not very large, the scaling of resistivity is predominantly controlled by the HD susceptibility and chaos; otherwise more physics is required.展开更多
This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode...This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode of inhibition of photosynthetic electron transport chain of both the algae was similar, PS II depicted greater sensitivity to the test metals used. The toxicity in both organisms was Cu > Ni > Fe. A. doliolum was, however, more sensitive to Cu and Ni, and C. vulgaris to Fe. Toxicity was generally dependent on metal uptake, which in turn was dependent on their concentrations in the external medium. A partial restoration of nutrient uptake, carbon fixation, and enzyme activities following supplementation of exogenous ATP suggests that ATP regulates toxicity through chelation.展开更多
The dynamical process of charge injection from metal electrode to a nondegenerate polymer in a metal/polythiophene (PT)/metal structure has been investigated by using a nonadiabatic dynamic approach. It is found tha...The dynamical process of charge injection from metal electrode to a nondegenerate polymer in a metal/polythiophene (PT)/metal structure has been investigated by using a nonadiabatic dynamic approach. It is found that the injected charges form wave packets due to the strong electron-lattice interaction in PT. We demonstrate that the dynamical formation of the wave packet sensitively depends on the strength of applied voltage, the electric field, and the contact between PT and electrode. At a strength of the electric field more than 3.0 × 10^4 V/cm, the carriers can be ejected from the PT into the right electrode. At an electric field more than 3.0 × 10^5 V/cm, the wave packet cannot form while it moves rapidly to the right PT/metal interface. It is shown that the ejected quantity of charge is noninteger.展开更多
This study focuses on experiments of Au and Cu dissolved in vapor phase in hydrothermal fluids. Experiments prove that Au and Cu can re-distribute in vapor phase and liquid phase during separation of Au- and Cu-bearin...This study focuses on experiments of Au and Cu dissolved in vapor phase in hydrothermal fluids. Experiments prove that Au and Cu can re-distribute in vapor phase and liquid phase during separation of Au- and Cu-bearing supercritical fluids to vapor and liquid phases. These experimental results can illustrate some ore geneses, where boiling phenomena of ore fluids were found. Au- and Cubearing NaHCO3-HCl solutions were heated up to more than 350℃ in the main vessel, and then passed through a phase separator in a temperature range from 250℃ to 300℃, separated into vapor and liquid phases. We collected and analyzed the liquid and vapor samples separately, and found that Au and Cu dissolved and distributed in vapor phase. In some cases, the concentrations of Au and Cu in vapor are higher than those in liquid phase. Those experiments are used to interpret field observations of fluid inclusion data of some Au and Cu deposits, and demonstrate that some Au and Cu ore deposits are derived from metals transportation in vapor phase.展开更多
Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water,...Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1(IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1(IRE) m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1(IRE). Conclusion These results suggest that Pb is transported into the brain through DMT1(IRE), and the ERK MAPK pathway is involved in DMT1(IRE)-mediated transport regulation in brain vascular system in vivo.展开更多
【目的】Heavy metal ATPase(HMA)基因家族广泛参与植物对金属元素的吸收和转运,系统鉴定番茄HMA基因家族成员及其特征,并研究其在应对镉胁迫过程中的功能,为解析番茄重金属转运机制及番茄低镉积累种质创新提供理论依据。【方法】通过...【目的】Heavy metal ATPase(HMA)基因家族广泛参与植物对金属元素的吸收和转运,系统鉴定番茄HMA基因家族成员及其特征,并研究其在应对镉胁迫过程中的功能,为解析番茄重金属转运机制及番茄低镉积累种质创新提供理论依据。【方法】通过生物信息学鉴定番茄HMA基因家族成员,并分析其系统进化树、蛋白理化性质、基因结构、顺式作用元件、基因表达模式等,通过酵母功能互补试验研究SlHMA1的镉转运活性。【结果】番茄基因组中存在8个SlHMAs,分属2个亚组。在基因结构方面,各SlHMAs间及与拟南芥和水稻的同源基因之间都存在显著差异。SlHMAs成员启动子区域含有较多逆境响应相关的顺式作用元件,RT-qPCR结果也揭示大多数SlHMAs表达对镉胁迫有不同程度的组织特异性响应。酵母功能互补试验表明SlHMA1蛋白具有镉转运活性,进化分析表明HMA1广泛存在于植物界,且其ATP水解酶活性相关的氨基酸保守基序DKTGT也在植物界高度保守。【结论】番茄SlHMAs具有HMA家族基因的典型特征,同时也存在功能多样性。SlHMAs及其氨基酸保守基序DKTGT与金属离子转运及镉胁迫响应密切相关,在低镉作物育种方面具有重要应用潜力。展开更多
基金the Scientific Research Common Program of Beijing Municipal Commission of Education,No.KM200610025008
文摘Extensive iron deposition has been observed in the midbrain substantia nigra (SN) of Parkinson's disease (PD) patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study investigated the relationship between dopaminergic neuronal damage, iron content changes, and divalent metal transporter 1 (DMT1) in the midbrain SN of PD rats to explore the relationship between time of iron deposition and DMT1 expression. Frozen midbrain SN sections from model rats were stained with Perls' iron. Results showed massive loss of tyrosine hydroxylase (TH)-positive cells in the SN and increased DMT1 expression in model group rats. No obvious iron deposition was observed in the SN during early stages after damage, but significant iron deposition was detected at 8 weeks post-injury. Results demonstrate that the loss of TH-positive cells in the SN appeared simultaneously with increased DMT1 expression. Extensive iron deposition occurred at 8 weeks post injury, which could be regarded as an early time window of iron deposition.
基金We thank Dr Wei-dong Le for providing the MES23.5 cell line. This work was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Tech- nology of China (2006CB500704), the National Natural Science Foundation of China (30930036, 30770757, 30870858) and the Natural Science Fund of Shandong Province for Distinguished Young Scholars (JQ200807).
文摘Iron plays a key role in Parkinson's disease (PD). Increased iron content of the substantia nigra (SN) has been found in PD patients, and divalent metal transporter 1 (DMT1) has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine (6-OHDA)-induced PD rats, DMT1 with the iron responsive element (IRE, DMTI+IRE), but not DMT1 without IRE (DMTI-IRE), was up- regulated, suggesting that increased DMTI+IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMTl+IRE-over-expressing MES23.5 cells. In 6-OHDA-treated MES23.5 cells, increased iron regulatory protein (IRP) 1 and IRP2 expression was observed, while silencing of IRPs dramatically diminished 6-OHDA-indueed DMTI+IRE up-regulation. Pre- treatment with N-acetyl-L-cysteine fully suppressed IRPs up-regulation by inhibition of 6-OHDA-indueed oxidative stress. Increased DMTI+IRE expression resulted in increased iron influx by MES23.5 cells. Our data provide direct evidence that DMTI+IRE up-regulation can account for IRE/IRP-dependent 6-OHDA-induced iron accumulation initiated by 6-OHDA-induced intracellular oxidative stress and that increased levels of intracellular iron result in ag- gravated oxidative stress. The results of this study provide novel evidence supporting the use of anti-oxidants in the treatment of PD, with the goal of inhibiting iron accumulation by regulation of DMT1 expression.
基金Supported by"2009 Clinical and Basic Clinical Research Contest"of the Bureau for Clinical Research Support from the University of Chile Clinical Hospital
文摘AIM:To describe the variation that divalent metaltransporter 1(DMT1)shows in patients after Rouxen-Y gastric bypass(RYGB)surgery.METHODS:Prospective and analytical study of DMT1level at the brush border of proximal jejunum in patients having undergone RYGB surgery.The mucosa of proximal jejunum forming the gastrojejunal anastomosis was biopsied during surgery and after 6 mo later with an endoscopic biopsy.All the patients received precise instructions regarding feeding and nutritional supplementation.Both samples were processed at the same time by immunohistochemistry and western blot.Samples were analysed by a pathologist.For statistical analysis,theχ2 and Wilcoxon tests were used.RESULTS:Sixteen patients were recruited,13 of whom completed the study.Twelve were women.Average age and body mass index(BMI)were 44.1 and 40.4,respectively.Both body weight and BMI decreased significantly during the study period,with an average percent excess weight loss(%EWL)of 60%±13.3%and an average percent excess BMI loss(%EBMIL)of 79.6%±21.6%.Only two patients presented with mild anaemia6 mo after surgery,but their ferritin levels stayed within normal ranges.Staining for DMT1 showed a significant increase in the cytoplasm of enterocytes located at the tips of the villi(χ2=6.03;P=0.049).Nevertheless,the total quantity of DMT1 decreased significantly(Z=2.04;P=0.04).Associated with these results,we observed a significant increase in goblet cells in the villi 6mo postoperatively(Z=-2.47;P=0.013).CONCLUSION:Six months after RYGB surgery,patients exhibit an increase in DMT1 expression in the enterocytes of the tips of the villi at the proximal jejunum.
文摘There is no enough information about metal transport parameters in residual soil. These soils are generally structured and still there is no answer to what happens with the contaminant transport parameters when an acid solution with metal percolates this material with different structure. The objective of this study was to determine the contaminant transport parameters for Cd, Ni, Cu and Zn metals in an acid multispecies solution to a residual soil from south Brazil with an undisturbed and remolded structure. Column tests were carried out to determine the kd, Rd, Dh transport parameters. It was possible conclude that the magnitude of the kd, Rd and Dh parameter did not vary significantly with the soil structure.
文摘The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
基金Supported by National Natural Science Foundation of China under Grant No.11675097
文摘We study a particular combination of charge and heat currents, which is decoupled with the heat current.The "heat-decoupled"(HD) current can be transported by diffusion at long distances, when the thermoelectric effect is small, large, or balanced. Using holographic models with momentum relaxation, we illustrate that the different thermoelectric effects correspond to the high temperatures and strong disorder, low temperatures, or special critical index. Meanwhile, the Einstein-like relation and the diffusion/chaos relation may be emergent. Assuming that the existence and features of HD modes appear in strange metals, we can predict that when the thermoelectric effect is not very large, the scaling of resistivity is predominantly controlled by the HD susceptibility and chaos; otherwise more physics is required.
文摘This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode of inhibition of photosynthetic electron transport chain of both the algae was similar, PS II depicted greater sensitivity to the test metals used. The toxicity in both organisms was Cu > Ni > Fe. A. doliolum was, however, more sensitive to Cu and Ni, and C. vulgaris to Fe. Toxicity was generally dependent on metal uptake, which in turn was dependent on their concentrations in the external medium. A partial restoration of nutrient uptake, carbon fixation, and enzyme activities following supplementation of exogenous ATP suggests that ATP regulates toxicity through chelation.
基金Project supported by the State Key Program of National Natural Science of China (Grant Nos 10474056 and 10574082)the Natural Science Foundation of Shandong Province (Grant No Z2005A01)
文摘The dynamical process of charge injection from metal electrode to a nondegenerate polymer in a metal/polythiophene (PT)/metal structure has been investigated by using a nonadiabatic dynamic approach. It is found that the injected charges form wave packets due to the strong electron-lattice interaction in PT. We demonstrate that the dynamical formation of the wave packet sensitively depends on the strength of applied voltage, the electric field, and the contact between PT and electrode. At a strength of the electric field more than 3.0 × 10^4 V/cm, the carriers can be ejected from the PT into the right electrode. At an electric field more than 3.0 × 10^5 V/cm, the wave packet cannot form while it moves rapidly to the right PT/metal interface. It is shown that the ejected quantity of charge is noninteger.
文摘This study focuses on experiments of Au and Cu dissolved in vapor phase in hydrothermal fluids. Experiments prove that Au and Cu can re-distribute in vapor phase and liquid phase during separation of Au- and Cu-bearing supercritical fluids to vapor and liquid phases. These experimental results can illustrate some ore geneses, where boiling phenomena of ore fluids were found. Au- and Cubearing NaHCO3-HCl solutions were heated up to more than 350℃ in the main vessel, and then passed through a phase separator in a temperature range from 250℃ to 300℃, separated into vapor and liquid phases. We collected and analyzed the liquid and vapor samples separately, and found that Au and Cu dissolved and distributed in vapor phase. In some cases, the concentrations of Au and Cu in vapor are higher than those in liquid phase. Those experiments are used to interpret field observations of fluid inclusion data of some Au and Cu deposits, and demonstrate that some Au and Cu ore deposits are derived from metals transportation in vapor phase.
基金supported by National Natural Science Foundation of China(No.81472478)Medical Science Youth Breeding Project of PLA(13QNP161)
文摘Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1(IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1(IRE) m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1(IRE). Conclusion These results suggest that Pb is transported into the brain through DMT1(IRE), and the ERK MAPK pathway is involved in DMT1(IRE)-mediated transport regulation in brain vascular system in vivo.
文摘【目的】Heavy metal ATPase(HMA)基因家族广泛参与植物对金属元素的吸收和转运,系统鉴定番茄HMA基因家族成员及其特征,并研究其在应对镉胁迫过程中的功能,为解析番茄重金属转运机制及番茄低镉积累种质创新提供理论依据。【方法】通过生物信息学鉴定番茄HMA基因家族成员,并分析其系统进化树、蛋白理化性质、基因结构、顺式作用元件、基因表达模式等,通过酵母功能互补试验研究SlHMA1的镉转运活性。【结果】番茄基因组中存在8个SlHMAs,分属2个亚组。在基因结构方面,各SlHMAs间及与拟南芥和水稻的同源基因之间都存在显著差异。SlHMAs成员启动子区域含有较多逆境响应相关的顺式作用元件,RT-qPCR结果也揭示大多数SlHMAs表达对镉胁迫有不同程度的组织特异性响应。酵母功能互补试验表明SlHMA1蛋白具有镉转运活性,进化分析表明HMA1广泛存在于植物界,且其ATP水解酶活性相关的氨基酸保守基序DKTGT也在植物界高度保守。【结论】番茄SlHMAs具有HMA家族基因的典型特征,同时也存在功能多样性。SlHMAs及其氨基酸保守基序DKTGT与金属离子转运及镉胁迫响应密切相关,在低镉作物育种方面具有重要应用潜力。
基金Project(2019YFC1803601)supported by the National Key Research and Development Program of ChinaProject(GCC[2023]038)supported by Guizhou“Hundred”High-level Innovative Talent Project,China。