GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address th...GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.展开更多
The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
Land transport can no longer meet the requirements.European transport can be described by these words−crowded motorways and cities,dangerous emissions,ubiquitous traffic accidents,delays,expensive railways.Solutions a...Land transport can no longer meet the requirements.European transport can be described by these words−crowded motorways and cities,dangerous emissions,ubiquitous traffic accidents,delays,expensive railways.Solutions are being sought to transfer a large part of passengers and especially freight transport to(high-speed)rail,and efforts are moving towards electromobility,car-sharing,5G-connectivity,autonomous driving,MaaS(Mobility as a Service)-coordinated transport or hyperloop-type solutions.However,all these solutions have additional challenges and limitations.Solutions are not being searched where they really exist-in the mutual adaptation of road and rail vehicles and their deep cooperation.The ComplexTrans project shows that simply adapting the dimensions and functions of road and rail vehicles can eliminate(or at least significantly reduce)all the problems of existing land transport.The main features of the ComplexTrans system are sufficient parking spaces,reduction of urban and non-urban congestion,electric vehicles with unlimited range and cheaper than standard cars,cheaper and more accessible battery charging,“autonomous ride”,solving the overlap between passenger and freight rail transport and making it self-financing,transferring intercity freight transport to rail,replacing part of continental air transport and many others.The cost-effective and clustered individual transport and individualised public transport of the ComplexTrans system also bring very significant reductions in the risk of transmission of covid-19 and other contagious diseases during transport.展开更多
In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epice...In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.展开更多
There is still no effective means to analyze in depth and utilize domestic mass data about agricultural product quality safety tests in china now. The neural network algorithm, the classification regression tree algor...There is still no effective means to analyze in depth and utilize domestic mass data about agricultural product quality safety tests in china now. The neural network algorithm, the classification regression tree algorithm, the Bayesian network algorithm were selected according to the principle of selecting combination model and were used to build models respectively and then combined, innovatively establishing a combination model which has relatively high precision, strong robustness and better explanatory to predict the results of perishable food transportation meta-morphism monitoring. The relative optimal prediction model of the perishable food transportation metamorphism monitoring system could be got. The relative perfect prediction model can guide the actual sampling work about food quality and safety by prognosticating the occurrence of unqualified food to select the typical and effective samples for test, thus improving the efficiency and effectiveness of sampling work effectively, so as to avoid deteriorated perishable food’s approaching the market to ensure the quality and safety of perishable food transportation. A solid protective wall was built in the protection of general perishable food consumers’ health.展开更多
A large specific surface area perovskite-type mixed oxide PbTiO3 supported cupric oxide was synthesized as a catalyst for NO decomposition and characterized by techniques such as XPS, XRD, H2-TPR before and after NO d...A large specific surface area perovskite-type mixed oxide PbTiO3 supported cupric oxide was synthesized as a catalyst for NO decomposition and characterized by techniques such as XPS, XRD, H2-TPR before and after NO decomposition reactions. The catalytic properties were tested with a fix-bed micro-reactor. The results showed that the PbTiO3 was inactive for the reactions, but 1wt % Cu/PbTiO3 catalyst gave fairly good activities for NO decomposition at temperature as low as 473 K. Copper species were found well-dispersed but weakly interacted with the support before NO decomposition, and the NO decomposition caused significant change in the environment of the copper species, which became Cu(Ⅰ)and most probably incorporated into surface crystal lattice of the nano-sized PbTiO3. In NO reaction, a large amount of oxygen atoms from the decomposition of NO penetrated into the nano-sized PbTiO3 support and caused small expansion of crystal lattice. The transport of oxygen between the copper species and the catalyst support may be helpful to speed up the kinetic regeneration of active metal sites from oxygen occupancy and resulted in good catalytic performance.展开更多
In recent Japan, as there has been an increase of dual-income households and the demand for childcare facilities has especially increased especially in urban areas, childcare facilities and workers are lacking and it ...In recent Japan, as there has been an increase of dual-income households and the demand for childcare facilities has especially increased especially in urban areas, childcare facilities and workers are lacking and it leads to the serious issue of children on waiting lists. Based on the background mentioned above, using statistical method, geographical information system (GIS) and public open data, scenario analysis to select transportation, the present study aimed to propose a method to quantitatively evaluate the current location of childcare facilities in Japanese urban areas. In the present study, the model of the p-median problem used to obtain the optimal location of facilities was modified, and a method to evaluate the current situation concerning the shortage or overage of childcare facilities by district was proposed. As evaluations are conducted using quantitative data such as the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts, the evaluation results are also quantitative, making it an effective indicator for evaluating the locations of childcare facilities. Additionally, the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts were calculated based on public open data. Therefore, the evaluation method in the present study has a high temporal reproducibility as well as spatial reproducibility.展开更多
Method is developed for self-consistent calculation of the energy spectrum of free energy and electrical disordered crystals. Processes of electron scattering on the ionic core potential of different sort, fluctuation...Method is developed for self-consistent calculation of the energy spectrum of free energy and electrical disordered crystals. Processes of electron scattering on the ionic core potential of different sort, fluctuations of charge, spin density and lattice vibrations are taken into account. Electronic states of the system are described using tight binding multiband model. The nature of the spin-dependent electron transport of carbon nanotubes with chromium atoms adsorbed on the surface is explained. The value of the spin polarization of electron transport is determined by the difference of the partial densities of states of electrons with opposite spin projection at the Fermi level and the difference between the relaxation times of electron states. The value of the spin polarization of the electric current increases with increasing of Cr atoms concentration and magnitude of the external magnetic field.展开更多
Phosphatidylglycerol (PG) an important membrane phospholipid required for the synthesis of diphos-phatidylglycerol (DPG) commonly known as cardiolipin (CL) was identified in the fraction of endo-plasmic reticulum (ER)...Phosphatidylglycerol (PG) an important membrane phospholipid required for the synthesis of diphos-phatidylglycerol (DPG) commonly known as cardiolipin (CL) was identified in the fraction of endo-plasmic reticulum (ER)-derived transport vesicles which had no affinity for Golgi. The vesicles were produced in the presence of Brefeldin A (BFA), the agent known to inhibit ER-Golgi transport, and found to display affinity to mitochondria. The analysis revealed that their cargo was not containing proteins that are transported to Golgi, and that their membrane was free of phosphatidylinositol (PI) and ceramides (Cer). The incubation of PG-containing transport vesicles with mitochondria afforded incorporation of their membrane into the Outer Mito-chondrial Membrane (OMM) and formation of lyso-phosphatidylglycerol (LPG). In turn, upon further incubation with fresh transport active cytosol, the mitochondrial LPG was converted to PG. The results of analysis of the OMM, Inner Mitochondrial Mem-brane (IMM) and Inner Mitochondrial Space Components (IMSC) strongly suggest that PG-containing transport vesicles deliver nuclear DNA translation products to the IMSC and thus facilitate CL synthesis in the IMM. In summary, our studies provide evidence that ER-generated PG-enriched transport vesicles represent the general pathway for restitution of mitochondrial membranes and the delivery of nuclear DNA translation products that generate CL, and thus sustain the mitochondrial matrix CL-dependent metabolic reactions.展开更多
Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-...Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.展开更多
The purpose of this study was to evaluate the ability of aqueous extract of Aloe barbadensis Miller (Aloe vera) on oxidative damage and Anion Exchanger 1 (AE1, also known as Band 3) expression in human erythrocytes ex...The purpose of this study was to evaluate the ability of aqueous extract of Aloe barbadensis Miller (Aloe vera) on oxidative damage and Anion Exchanger 1 (AE1, also known as Band 3) expression in human erythrocytes exposed to the water soluble free radical initiator 2.2’-azobis-2-amidinopropano dihydrochloride (AAPH). In addition, total phenolic compounds in the extracts were determined as catechin equivalent and the various antioxidant activities were compared to natural and synthetic standard antioxidants such as BHA and ascorbic acid. Since Aloe vera extract did not cause a consumption of the cytosolic antioxidant, glutathione (GSH) when it was direct incubated with GSH in basic aerated aqueous solution, this indicates that Aloe vera extract does not proceed auto oxidation at this experimental condition. Furthermore, Aloe vera extract prevent the consumption of GSH, in radical treated RBCs. It also inhibit consumption of GSH when it was direct incubated with AAPH. Aloe vera gel extract inhibits the generation of diphenyl-2-picrylhy-drazyl (DPPH) and the scavenging activity was increased in a dose dependent manner. Aloe vera extract was shown the similar reducing power than standards BHT and ascorbic acid. Biochemical analysis by SDS-PAGE and western blotting showed that AAPH-induced oxidative stress increased the susceptibility of AE1 to proteolytic degradation. Of note, our data evidenced that Aloe vera treatment was able to partially restore the normal RBC membrane protein profiles in a dose-dependent manner. These results clearly demonstrate the antioxidative activity of Aloe vera gel extract that might be ascribed to a synergistic action of the bioactive compounds contained therein.展开更多
AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile a...AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids.Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains undear.Thus,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative immunoblotting.The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet.In contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet.In the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet.As anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microperfused IBDUs derived from rats on TCA diet decreased 2.7-fold,whereas it increased 1.7-fold in those on CY diet compared to C diet fed groups. CONCLUSION: These data demonstrate that expression of ASBT and t-ASBT in cholangiocytes is regulated by a negative feedback loop while the expression of these transporters in terminal ileum is modified via positive feedback.Thus, while transcriptional regulatory mechanisms in response to alterations in bile acid pool size are operative in both cholangiocytes and ileocytes,each cell type responds differently to bile acid supplementation and depletion.展开更多
In this article a new approach is considered for implementing operator splitting methods for transport problems, influenced by electric fields. Our motivation came to model PE-CVD (plasma-enhanced chemical vapor depos...In this article a new approach is considered for implementing operator splitting methods for transport problems, influenced by electric fields. Our motivation came to model PE-CVD (plasma-enhanced chemical vapor deposition) processes, means the flow of species to a gas-phase, which are influenced by an electric field. Such a field we can model by wave equations. The main contributions are to improve the standard discretization schemes of each part of the coupling equation. So we discuss an improvement with implicit Runge- Kutta methods instead of the Yee’s algorithm. Further we balance the solver method between the Maxwell and Transport equation.展开更多
Given the seriously damaged emergency situation occurring after a large-scale natural disaster, a critical and important problem that needs to be solved urgently is how to distribute the necessary relief goods, such a...Given the seriously damaged emergency situation occurring after a large-scale natural disaster, a critical and important problem that needs to be solved urgently is how to distribute the necessary relief goods, such as drinking water, food, and medicine, to the damaged area and how to transport them corresponding to the actual supply and demand situation as quickly as possible. The existing infrastructure, such as traffic roads, bridges, buildings, and other facilities, may suffer from severe damage. Assuming uncertainty related with each road segment’s availability, we formulate a transshipment network flow optimization problem under various types of uncertain situations. In order to express the uncertainty regarding the availability of each road segment, we apply the Monte Carlo simulation technique to generate random networks following certain probability distribution conditions. Then, we solve the model to obtain an optimal transport strategy for the relief goods. Thus, we try to implement a necessary and desirable response strategy for managing emergency cases caused by, for example, various natural disasters. Our modeling approach was then applied to the actual road network in Sumatra Island in Indonesia in 2009, when a disastrous earthquake occurred to develop effective and efficient public policies for emergency situations.展开更多
We previously reported that intranasal insulin protects substantia nigra dopaminergic neurons against6-hydroxydopamine neurotoxicity in rats. This study aimed to assess insulin pharmacokinetics in the rat brain follow...We previously reported that intranasal insulin protects substantia nigra dopaminergic neurons against6-hydroxydopamine neurotoxicity in rats. This study aimed to assess insulin pharmacokinetics in the rat brain following intranasal application. Recombinant human insulin(rh-Ins) or phosphate buffer solution was administered to both nostrils of rats. Animals were sacrificed at 15 minutes, 1, 2, and 6 hours to determine insulin levels in different brain regions by an ultrasensitive, human-specific enzyme-linked immunosorbent assay kit. For fluorescence tracing study, rats were administered with intranasal florescence-tagged insulin(Alex546-Ins), and brains were fixed at 10 and 30 minutes to prepare sagittal sections.rh-Ins was detected in all brain regions examined except the cerebral cortex. The highest levels were detected in the brainstem, followed by the cerebellum, substantia nigra/ventral tegmental area, olfactory bulb,striatum, hippocampus, and thalamus/hypothalamus. Insulin levels reached a peak at 15 minutes and then declined gradually overtime, but remained significantly higher than baseline levels at 6 hours in most regions.Consistently, widespread Alex546-Ins-binding cells were detected in the brain at 10 and 30 minutes, with the olfactory bulb and brainstem showing the highest while the cerebral cortex showing lowest fluorescence signals. Double-immunostaining showed that Alex546-Ins-bindings were primarily co-localized with neuronal nuclei-positive neurons. In the subtantia nigra, phospho-Akt was found to be activated in a subset of Alex546-Ins and tyrosine hydroxylase double-labeled cells, suggesting activation of the Akt/PI3 K pathway in these dopaminergic neurons. Data from this study suggest that intranasal insulin could effectively reach deep brain structures including the nigrostriatal pathways, where it binds to dopaminergic neurons and activates intracellular cell survival signaling. This study was approved by the Institutional Animal Care Committee at the University of Mississippi Medical Center(protocol 1333 A) on June 29, 2015.展开更多
Historical mining activities often lead to continuing wide spread contaminants in both groundwater and surface water in previously operational mine site areas. The contamination may continue for many years after closi...Historical mining activities often lead to continuing wide spread contaminants in both groundwater and surface water in previously operational mine site areas. The contamination may continue for many years after closing down the mining activities. The essential first step for sustainable management of groundwater and development of remediation strategies is the unknown contaminant source characterization. In a mining site, there are multiple species of contaminants involving complex geochemical processes. It is difficult to identify the potential sources and pathways incorporating the chemically reactive multiple species of contaminants making the source characterization process more challenging. To address this issue, a reactive transport simulation model PHT3D is linked to a Simulated Annealing based the optimum decision model. The numerical simulation model PHT3D is utilized for numerically simulating the reactive transport process involving multiple species in the former mine site area. The simulation results from the calibrated PHT3D model are illustrated, with and without incorporating the chemical reactions. These comparisons show the utility of using a reactive, geochemical transport process’ simulation model. Performance evaluation of the linked simulation optimization methodology is evaluated for a contamination scenario in a former mine site in Queensland, Australia. These performance evaluation results illustrate the applicability of linked simulation optimization model to identify the source characteristics while using PHT3D as a numerical reactive chemical species’ transport simulation model for the hydro-geochemically complex aquifer study area.展开更多
HIV-1 matrix protein (MA) is a multifunctional structural protein localized on N terminus of Gag precursor p55. MA participates in HIV-1 assembly as membranotropic part of Gag precursor as well as an individual protei...HIV-1 matrix protein (MA) is a multifunctional structural protein localized on N terminus of Gag precursor p55. MA participates in HIV-1 assembly as membranotropic part of Gag precursor as well as an individual protein spliced from Gag early in infection. MA is found in the nuclei of infected cells and in plasma membrane, the site of virus assembly, in association with viral genome RNA. MA mutated variant M4 which contains two changed amino acids in N-terminal regions is also associated with viral RNA, but it is localized in the nuclear and cytoskeleton fractions but not in the plasma membrane suggesting that the mutant is deprived of membranotropic signal and “sticks” in the nuclei an d cytoskeleton, its previous location sites. These data allow suggesting that MA involved into transmission of viral RNA is transported to plasma membrane by cytoskeleton.展开更多
基金foundations from Chinese Academy of Sciences and Special Funds for Major State Basic reseaxch of China (G1999053903).
文摘GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金This research is partly supported by project SGS-2019-001The 3-D visualisations were prepared by students of University of West Bohemia or by professional designers.
文摘Land transport can no longer meet the requirements.European transport can be described by these words−crowded motorways and cities,dangerous emissions,ubiquitous traffic accidents,delays,expensive railways.Solutions are being sought to transfer a large part of passengers and especially freight transport to(high-speed)rail,and efforts are moving towards electromobility,car-sharing,5G-connectivity,autonomous driving,MaaS(Mobility as a Service)-coordinated transport or hyperloop-type solutions.However,all these solutions have additional challenges and limitations.Solutions are not being searched where they really exist-in the mutual adaptation of road and rail vehicles and their deep cooperation.The ComplexTrans project shows that simply adapting the dimensions and functions of road and rail vehicles can eliminate(or at least significantly reduce)all the problems of existing land transport.The main features of the ComplexTrans system are sufficient parking spaces,reduction of urban and non-urban congestion,electric vehicles with unlimited range and cheaper than standard cars,cheaper and more accessible battery charging,“autonomous ride”,solving the overlap between passenger and freight rail transport and making it self-financing,transferring intercity freight transport to rail,replacing part of continental air transport and many others.The cost-effective and clustered individual transport and individualised public transport of the ComplexTrans system also bring very significant reductions in the risk of transmission of covid-19 and other contagious diseases during transport.
基金supported by COBRE(P30GM149367)the Puerto Rico Science&Technology Trust(2022-00125)+1 种基金MBRS-RISE Program(R25 GM061838)SC1GM144032 program(all to JDM)。
文摘In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.
文摘There is still no effective means to analyze in depth and utilize domestic mass data about agricultural product quality safety tests in china now. The neural network algorithm, the classification regression tree algorithm, the Bayesian network algorithm were selected according to the principle of selecting combination model and were used to build models respectively and then combined, innovatively establishing a combination model which has relatively high precision, strong robustness and better explanatory to predict the results of perishable food transportation meta-morphism monitoring. The relative optimal prediction model of the perishable food transportation metamorphism monitoring system could be got. The relative perfect prediction model can guide the actual sampling work about food quality and safety by prognosticating the occurrence of unqualified food to select the typical and effective samples for test, thus improving the efficiency and effectiveness of sampling work effectively, so as to avoid deteriorated perishable food’s approaching the market to ensure the quality and safety of perishable food transportation. A solid protective wall was built in the protection of general perishable food consumers’ health.
文摘A large specific surface area perovskite-type mixed oxide PbTiO3 supported cupric oxide was synthesized as a catalyst for NO decomposition and characterized by techniques such as XPS, XRD, H2-TPR before and after NO decomposition reactions. The catalytic properties were tested with a fix-bed micro-reactor. The results showed that the PbTiO3 was inactive for the reactions, but 1wt % Cu/PbTiO3 catalyst gave fairly good activities for NO decomposition at temperature as low as 473 K. Copper species were found well-dispersed but weakly interacted with the support before NO decomposition, and the NO decomposition caused significant change in the environment of the copper species, which became Cu(Ⅰ)and most probably incorporated into surface crystal lattice of the nano-sized PbTiO3. In NO reaction, a large amount of oxygen atoms from the decomposition of NO penetrated into the nano-sized PbTiO3 support and caused small expansion of crystal lattice. The transport of oxygen between the copper species and the catalyst support may be helpful to speed up the kinetic regeneration of active metal sites from oxygen occupancy and resulted in good catalytic performance.
文摘In recent Japan, as there has been an increase of dual-income households and the demand for childcare facilities has especially increased especially in urban areas, childcare facilities and workers are lacking and it leads to the serious issue of children on waiting lists. Based on the background mentioned above, using statistical method, geographical information system (GIS) and public open data, scenario analysis to select transportation, the present study aimed to propose a method to quantitatively evaluate the current location of childcare facilities in Japanese urban areas. In the present study, the model of the p-median problem used to obtain the optimal location of facilities was modified, and a method to evaluate the current situation concerning the shortage or overage of childcare facilities by district was proposed. As evaluations are conducted using quantitative data such as the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts, the evaluation results are also quantitative, making it an effective indicator for evaluating the locations of childcare facilities. Additionally, the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts were calculated based on public open data. Therefore, the evaluation method in the present study has a high temporal reproducibility as well as spatial reproducibility.
文摘Method is developed for self-consistent calculation of the energy spectrum of free energy and electrical disordered crystals. Processes of electron scattering on the ionic core potential of different sort, fluctuations of charge, spin density and lattice vibrations are taken into account. Electronic states of the system are described using tight binding multiband model. The nature of the spin-dependent electron transport of carbon nanotubes with chromium atoms adsorbed on the surface is explained. The value of the spin polarization of electron transport is determined by the difference of the partial densities of states of electrons with opposite spin projection at the Fermi level and the difference between the relaxation times of electron states. The value of the spin polarization of the electric current increases with increasing of Cr atoms concentration and magnitude of the external magnetic field.
文摘Phosphatidylglycerol (PG) an important membrane phospholipid required for the synthesis of diphos-phatidylglycerol (DPG) commonly known as cardiolipin (CL) was identified in the fraction of endo-plasmic reticulum (ER)-derived transport vesicles which had no affinity for Golgi. The vesicles were produced in the presence of Brefeldin A (BFA), the agent known to inhibit ER-Golgi transport, and found to display affinity to mitochondria. The analysis revealed that their cargo was not containing proteins that are transported to Golgi, and that their membrane was free of phosphatidylinositol (PI) and ceramides (Cer). The incubation of PG-containing transport vesicles with mitochondria afforded incorporation of their membrane into the Outer Mito-chondrial Membrane (OMM) and formation of lyso-phosphatidylglycerol (LPG). In turn, upon further incubation with fresh transport active cytosol, the mitochondrial LPG was converted to PG. The results of analysis of the OMM, Inner Mitochondrial Mem-brane (IMM) and Inner Mitochondrial Space Components (IMSC) strongly suggest that PG-containing transport vesicles deliver nuclear DNA translation products to the IMSC and thus facilitate CL synthesis in the IMM. In summary, our studies provide evidence that ER-generated PG-enriched transport vesicles represent the general pathway for restitution of mitochondrial membranes and the delivery of nuclear DNA translation products that generate CL, and thus sustain the mitochondrial matrix CL-dependent metabolic reactions.
文摘Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.
文摘The purpose of this study was to evaluate the ability of aqueous extract of Aloe barbadensis Miller (Aloe vera) on oxidative damage and Anion Exchanger 1 (AE1, also known as Band 3) expression in human erythrocytes exposed to the water soluble free radical initiator 2.2’-azobis-2-amidinopropano dihydrochloride (AAPH). In addition, total phenolic compounds in the extracts were determined as catechin equivalent and the various antioxidant activities were compared to natural and synthetic standard antioxidants such as BHA and ascorbic acid. Since Aloe vera extract did not cause a consumption of the cytosolic antioxidant, glutathione (GSH) when it was direct incubated with GSH in basic aerated aqueous solution, this indicates that Aloe vera extract does not proceed auto oxidation at this experimental condition. Furthermore, Aloe vera extract prevent the consumption of GSH, in radical treated RBCs. It also inhibit consumption of GSH when it was direct incubated with AAPH. Aloe vera gel extract inhibits the generation of diphenyl-2-picrylhy-drazyl (DPPH) and the scavenging activity was increased in a dose dependent manner. Aloe vera extract was shown the similar reducing power than standards BHT and ascorbic acid. Biochemical analysis by SDS-PAGE and western blotting showed that AAPH-induced oxidative stress increased the susceptibility of AE1 to proteolytic degradation. Of note, our data evidenced that Aloe vera treatment was able to partially restore the normal RBC membrane protein profiles in a dose-dependent manner. These results clearly demonstrate the antioxidative activity of Aloe vera gel extract that might be ascribed to a synergistic action of the bioactive compounds contained therein.
文摘AIM: We have previously demonstrated that cholangiocytes, the epithelial cells lining intrahepatic bile ducts,encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport. Cholangiocytes possess ASBT,an apical sodium-dependent bile acid transporter to take up bile acids,and t-ASBT,a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids.Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids, the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains undear.Thus,we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pair- fed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets,were assessed by both quantitative RNase protection assays and quantitative immunoblotting.The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets. Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C,TCA and CY fed rats. RESULTS: In cholangiocytes,both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet.In contrast, message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet.In the ileum,TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet,while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet.As anticipated from alterations in cholangiocyte ASBT expression,the uptake of taurocholate in microperfused IBDUs derived from rats on TCA diet decreased 2.7-fold,whereas it increased 1.7-fold in those on CY diet compared to C diet fed groups. CONCLUSION: These data demonstrate that expression of ASBT and t-ASBT in cholangiocytes is regulated by a negative feedback loop while the expression of these transporters in terminal ileum is modified via positive feedback.Thus, while transcriptional regulatory mechanisms in response to alterations in bile acid pool size are operative in both cholangiocytes and ileocytes,each cell type responds differently to bile acid supplementation and depletion.
文摘In this article a new approach is considered for implementing operator splitting methods for transport problems, influenced by electric fields. Our motivation came to model PE-CVD (plasma-enhanced chemical vapor deposition) processes, means the flow of species to a gas-phase, which are influenced by an electric field. Such a field we can model by wave equations. The main contributions are to improve the standard discretization schemes of each part of the coupling equation. So we discuss an improvement with implicit Runge- Kutta methods instead of the Yee’s algorithm. Further we balance the solver method between the Maxwell and Transport equation.
文摘Given the seriously damaged emergency situation occurring after a large-scale natural disaster, a critical and important problem that needs to be solved urgently is how to distribute the necessary relief goods, such as drinking water, food, and medicine, to the damaged area and how to transport them corresponding to the actual supply and demand situation as quickly as possible. The existing infrastructure, such as traffic roads, bridges, buildings, and other facilities, may suffer from severe damage. Assuming uncertainty related with each road segment’s availability, we formulate a transshipment network flow optimization problem under various types of uncertain situations. In order to express the uncertainty regarding the availability of each road segment, we apply the Monte Carlo simulation technique to generate random networks following certain probability distribution conditions. Then, we solve the model to obtain an optimal transport strategy for the relief goods. Thus, we try to implement a necessary and desirable response strategy for managing emergency cases caused by, for example, various natural disasters. Our modeling approach was then applied to the actual road network in Sumatra Island in Indonesia in 2009, when a disastrous earthquake occurred to develop effective and efficient public policies for emergency situations.
文摘We previously reported that intranasal insulin protects substantia nigra dopaminergic neurons against6-hydroxydopamine neurotoxicity in rats. This study aimed to assess insulin pharmacokinetics in the rat brain following intranasal application. Recombinant human insulin(rh-Ins) or phosphate buffer solution was administered to both nostrils of rats. Animals were sacrificed at 15 minutes, 1, 2, and 6 hours to determine insulin levels in different brain regions by an ultrasensitive, human-specific enzyme-linked immunosorbent assay kit. For fluorescence tracing study, rats were administered with intranasal florescence-tagged insulin(Alex546-Ins), and brains were fixed at 10 and 30 minutes to prepare sagittal sections.rh-Ins was detected in all brain regions examined except the cerebral cortex. The highest levels were detected in the brainstem, followed by the cerebellum, substantia nigra/ventral tegmental area, olfactory bulb,striatum, hippocampus, and thalamus/hypothalamus. Insulin levels reached a peak at 15 minutes and then declined gradually overtime, but remained significantly higher than baseline levels at 6 hours in most regions.Consistently, widespread Alex546-Ins-binding cells were detected in the brain at 10 and 30 minutes, with the olfactory bulb and brainstem showing the highest while the cerebral cortex showing lowest fluorescence signals. Double-immunostaining showed that Alex546-Ins-bindings were primarily co-localized with neuronal nuclei-positive neurons. In the subtantia nigra, phospho-Akt was found to be activated in a subset of Alex546-Ins and tyrosine hydroxylase double-labeled cells, suggesting activation of the Akt/PI3 K pathway in these dopaminergic neurons. Data from this study suggest that intranasal insulin could effectively reach deep brain structures including the nigrostriatal pathways, where it binds to dopaminergic neurons and activates intracellular cell survival signaling. This study was approved by the Institutional Animal Care Committee at the University of Mississippi Medical Center(protocol 1333 A) on June 29, 2015.
文摘Historical mining activities often lead to continuing wide spread contaminants in both groundwater and surface water in previously operational mine site areas. The contamination may continue for many years after closing down the mining activities. The essential first step for sustainable management of groundwater and development of remediation strategies is the unknown contaminant source characterization. In a mining site, there are multiple species of contaminants involving complex geochemical processes. It is difficult to identify the potential sources and pathways incorporating the chemically reactive multiple species of contaminants making the source characterization process more challenging. To address this issue, a reactive transport simulation model PHT3D is linked to a Simulated Annealing based the optimum decision model. The numerical simulation model PHT3D is utilized for numerically simulating the reactive transport process involving multiple species in the former mine site area. The simulation results from the calibrated PHT3D model are illustrated, with and without incorporating the chemical reactions. These comparisons show the utility of using a reactive, geochemical transport process’ simulation model. Performance evaluation of the linked simulation optimization methodology is evaluated for a contamination scenario in a former mine site in Queensland, Australia. These performance evaluation results illustrate the applicability of linked simulation optimization model to identify the source characteristics while using PHT3D as a numerical reactive chemical species’ transport simulation model for the hydro-geochemically complex aquifer study area.
文摘HIV-1 matrix protein (MA) is a multifunctional structural protein localized on N terminus of Gag precursor p55. MA participates in HIV-1 assembly as membranotropic part of Gag precursor as well as an individual protein spliced from Gag early in infection. MA is found in the nuclei of infected cells and in plasma membrane, the site of virus assembly, in association with viral genome RNA. MA mutated variant M4 which contains two changed amino acids in N-terminal regions is also associated with viral RNA, but it is localized in the nuclear and cytoskeleton fractions but not in the plasma membrane suggesting that the mutant is deprived of membranotropic signal and “sticks” in the nuclei an d cytoskeleton, its previous location sites. These data allow suggesting that MA involved into transmission of viral RNA is transported to plasma membrane by cytoskeleton.