The expression of different vascular endothelial growth factor (VEGF) genes was studied in glioma U87 cells with endoplasmic reticulum–nuclei-1 (ERN1) loss of function and its regulation by hypoxia and glutamine or g...The expression of different vascular endothelial growth factor (VEGF) genes was studied in glioma U87 cells with endoplasmic reticulum–nuclei-1 (ERN1) loss of function and its regulation by hypoxia and glutamine or glucose deprivation conditions as model of ischemia. The blockade of function of the ERN1 enzyme, which is a major sensor of endoplasmic reticulum stress, leads to a decrease of the VEGFA, VEGFB and VEGFC mRNA expression level. The level of VEGFA proteins also decreases at this experimental condition in the cytosolic fraction, but increases in the nuclear fraction. Hypoxia does not affect VEGFC and increases the expression level of VEGFA and VEGFB mRNA in both used cell types, however, the change was much less profound in cells with suppressed function of ERN1. The expression level of VEGFC mRNA decreases in both used cell types in glutamine deprivation condition, however, the change was more profound in control glioma cells. At the same time, the expression level of VEGFA mRNA increases and VEGFB—decreases in gluta-mine deprivation condition in control glioma cells only. Exposure of glioma cells to glucose deprivation condition increases VEGFB mRNA expression level in both used cell types;however, VEGFA—in control glioma cells only and VEGFC—in cells with ERN1 signaling enzyme loss of function only. Thus, the results of this study clearly demonstrated the down-regulation of the expression of all three VEGF genes in glioma cells with ERN1 loss of function which correlates to the suppressed angiogenesis and proliferation rate of these cells. Moreover, the effect of hy-poxia and glutamine or glucose deprivation condition on the expression level of all VEGF genes is different and mainly depends on ERN1 signaling enzyme function.展开更多
The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum—nuclei-1), the main endoplasmic reticulum st...The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum—nuclei-1), the main endoplasmic reticulum stress sensing and signaling enzyme. It was shown that a blockade of the ERN1 enzyme function increases the expression levels of retinoblastoma, retinoblastoma-like 1 and most retinoblastoma related genes: EID1, JARID1B, E2F1, E2F3, RBAP48 and CTIP, does not change RNF40 and RBAP46 and decreases KDM5A. We have also demonstrated that hypoxia reduces the expression levels of retinoblastoma, EID1, and E2F1 in ERN1-deficient glioma cells only. At the same time, the expression levels of retinoblastoma-like 1, E2F3, RBAP46, RBAP48 and CTIP decrease, while JARID1B and RBBP2 increase in both types of cells in hypoxic conditions, but the expression is much stronger in cells with suppressed function of ERN1. The expression level of JARID1B and KDM-5A mRNA is also enhanced in glutamine deprivation condition in both tested cell types, moreover, this effect is amplified by the blockade of the ERN1 enzyme function. The expression levels of retinoblastoma, EID1, RBAP48, and E2F3 are decreased in glutamine deprivation condition only in ERN1-deficient glioma cells, but RBL1, CTIP, RBAP46, and E2F1—in both tested cell types with more significant effect in ERN1-deficient cells. Glucose deprivation condition leads to a decrease of expression levels of retinoblastoma, RBL1, E2F3, RBAP46, and RBAP48 in both used cell types and of EID1 and E2F1 only in glioma cells with suppressed function of signaling enzyme ERN1. Thus, expression levels of retinoblastoma and most retinoblastoma-related genes are increased under a blockade of ERN1 enzyme function and significantly changed in hypoxia, glucose or glutamine deprivation conditions both in control U87 cells and ERN1-deficient cells, but inhibition of the unfolded protein response sensor ERN1 predominantly enhances these effects. Moreover, it is possible that the induction of the expression of retinoblastoma and most retinoblastoma-related genes after knockdown of ERN1 plays an important role in suppression of glioma proliferation.展开更多
Climatic anomalies not only attract the attention of specialists in climatology and meteorology, but also stimulate geological research, because climatic changes activate many geological processes: mudflow and landsli...Climatic anomalies not only attract the attention of specialists in climatology and meteorology, but also stimulate geological research, because climatic changes activate many geological processes: mudflow and landslide formation, erosion, weathering, etc. An increase in the activity of geological processes was clearly manifested in Tajikistan, 93% of which is occupied by mountain structures. As a result, this found expression in conducting new for that territory engineering-geonomic studies. Both the region as a whole and its individual parts can serve as models in the study of natural processes due to the diversity of landscape-climatic belts and zones. The report contains brief data on engineering-geonomic studies conducted in the Zeravshan river basin in connection with the intensification of mudflow processes.展开更多
The coast of southern Hainan Island is characterized by wide sandy embayments, which consist of ( i) drowned valleys bounded by steep bedrock hills and only locally receiving sediments, and embayments of various dimen...The coast of southern Hainan Island is characterized by wide sandy embayments, which consist of ( i) drowned valleys bounded by steep bedrock hills and only locally receiving sediments, and embayments of various dimensions covered either by (ii) alluvial-deltaic deposits or by (iii) sands of coastal beach ridges/barriers and associated elongated lagoons. During the late Tertiary-Pleistocene the area has experienced isostatic and eustatic movements associated with neotectonics and climatic changes. Such history isrecorded in terraces at various altitudes (SO, 40, 20 m asl) and sequences of coastal sand ridges/baymouth bars. The Holocene variations in sea level and climate are recorded in the dated coastal ridges, coral reef and beachrock. Conditions suitable for reef development started about 8000 a BP. The GPR profiles also show that the internal structures of the sand ridges have composite nature being formed by several superimposed secondary ridges.展开更多
Background:Motor adaptation relies on error-based learning for accurate movements in changing environ-ments.However,the neurophysiological mechanisms driving individual differences in performance are unclear.Transcran...Background:Motor adaptation relies on error-based learning for accurate movements in changing environ-ments.However,the neurophysiological mechanisms driving individual differences in performance are unclear.Transcranial magnetic stimulation(TMS)-evoked potential can provide a direct measure of cortical excitability.Objective:To investigate cortical excitability as a predictor of motor learning and motor adaptation in a robot-mediated forcefield.Methods:A group of 15 right-handed healthy participants(mean age 23 years)performed a robot-mediated forcefield perturbation task.There were two conditions:unperturbed non-adaptation and perturbed adapta-tion.TMS was applied in the resting state at baseline and following motor adaptation over the contralateral primary motor cortex(left M1).Electroencephalographic(EEG)activity was continuously recorded,and cortical excitability was measured by TMS-evoked potential(TEP).Motor learning was quantified by the motor learning index.Results:Larger error-related negativity(ERN)in fronto-central regions was associated with improved motor per-formance as measured by a reduction in trajectory errors.Baseline TEP N100 peak amplitude predicted motor learning(P=0.005),which was significantly attenuated relative to baseline(P=0.0018)following motor adap-tation.Conclusions:ERN reflected the formation of a predictive internal model adapted to the forcefield perturbation.Attenuation in TEP N100 amplitude reflected an increase in cortical excitability with motor adaptation reflecting neuroplastic changes in the sensorimotor cortex.TEP N100 is a potential biomarker for predicting the outcome in robot-mediated therapy and a mechanism to investigate psychomotor abnormalities in depression.展开更多
文摘The expression of different vascular endothelial growth factor (VEGF) genes was studied in glioma U87 cells with endoplasmic reticulum–nuclei-1 (ERN1) loss of function and its regulation by hypoxia and glutamine or glucose deprivation conditions as model of ischemia. The blockade of function of the ERN1 enzyme, which is a major sensor of endoplasmic reticulum stress, leads to a decrease of the VEGFA, VEGFB and VEGFC mRNA expression level. The level of VEGFA proteins also decreases at this experimental condition in the cytosolic fraction, but increases in the nuclear fraction. Hypoxia does not affect VEGFC and increases the expression level of VEGFA and VEGFB mRNA in both used cell types, however, the change was much less profound in cells with suppressed function of ERN1. The expression level of VEGFC mRNA decreases in both used cell types in glutamine deprivation condition, however, the change was more profound in control glioma cells. At the same time, the expression level of VEGFA mRNA increases and VEGFB—decreases in gluta-mine deprivation condition in control glioma cells only. Exposure of glioma cells to glucose deprivation condition increases VEGFB mRNA expression level in both used cell types;however, VEGFA—in control glioma cells only and VEGFC—in cells with ERN1 signaling enzyme loss of function only. Thus, the results of this study clearly demonstrated the down-regulation of the expression of all three VEGF genes in glioma cells with ERN1 loss of function which correlates to the suppressed angiogenesis and proliferation rate of these cells. Moreover, the effect of hy-poxia and glutamine or glucose deprivation condition on the expression level of all VEGF genes is different and mainly depends on ERN1 signaling enzyme function.
文摘The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum—nuclei-1), the main endoplasmic reticulum stress sensing and signaling enzyme. It was shown that a blockade of the ERN1 enzyme function increases the expression levels of retinoblastoma, retinoblastoma-like 1 and most retinoblastoma related genes: EID1, JARID1B, E2F1, E2F3, RBAP48 and CTIP, does not change RNF40 and RBAP46 and decreases KDM5A. We have also demonstrated that hypoxia reduces the expression levels of retinoblastoma, EID1, and E2F1 in ERN1-deficient glioma cells only. At the same time, the expression levels of retinoblastoma-like 1, E2F3, RBAP46, RBAP48 and CTIP decrease, while JARID1B and RBBP2 increase in both types of cells in hypoxic conditions, but the expression is much stronger in cells with suppressed function of ERN1. The expression level of JARID1B and KDM-5A mRNA is also enhanced in glutamine deprivation condition in both tested cell types, moreover, this effect is amplified by the blockade of the ERN1 enzyme function. The expression levels of retinoblastoma, EID1, RBAP48, and E2F3 are decreased in glutamine deprivation condition only in ERN1-deficient glioma cells, but RBL1, CTIP, RBAP46, and E2F1—in both tested cell types with more significant effect in ERN1-deficient cells. Glucose deprivation condition leads to a decrease of expression levels of retinoblastoma, RBL1, E2F3, RBAP46, and RBAP48 in both used cell types and of EID1 and E2F1 only in glioma cells with suppressed function of signaling enzyme ERN1. Thus, expression levels of retinoblastoma and most retinoblastoma-related genes are increased under a blockade of ERN1 enzyme function and significantly changed in hypoxia, glucose or glutamine deprivation conditions both in control U87 cells and ERN1-deficient cells, but inhibition of the unfolded protein response sensor ERN1 predominantly enhances these effects. Moreover, it is possible that the induction of the expression of retinoblastoma and most retinoblastoma-related genes after knockdown of ERN1 plays an important role in suppression of glioma proliferation.
文摘Climatic anomalies not only attract the attention of specialists in climatology and meteorology, but also stimulate geological research, because climatic changes activate many geological processes: mudflow and landslide formation, erosion, weathering, etc. An increase in the activity of geological processes was clearly manifested in Tajikistan, 93% of which is occupied by mountain structures. As a result, this found expression in conducting new for that territory engineering-geonomic studies. Both the region as a whole and its individual parts can serve as models in the study of natural processes due to the diversity of landscape-climatic belts and zones. The report contains brief data on engineering-geonomic studies conducted in the Zeravshan river basin in connection with the intensification of mudflow processes.
基金Concerned research works have got the powerful support from State Pilot Laboratory of Coast & Island Exploitation, Nanjing University, Most staffs from this lab have joined the series of fieldwork, and also done many kinds of indoor analyses. Recent stud
文摘The coast of southern Hainan Island is characterized by wide sandy embayments, which consist of ( i) drowned valleys bounded by steep bedrock hills and only locally receiving sediments, and embayments of various dimensions covered either by (ii) alluvial-deltaic deposits or by (iii) sands of coastal beach ridges/barriers and associated elongated lagoons. During the late Tertiary-Pleistocene the area has experienced isostatic and eustatic movements associated with neotectonics and climatic changes. Such history isrecorded in terraces at various altitudes (SO, 40, 20 m asl) and sequences of coastal sand ridges/baymouth bars. The Holocene variations in sea level and climate are recorded in the dated coastal ridges, coral reef and beachrock. Conditions suitable for reef development started about 8000 a BP. The GPR profiles also show that the internal structures of the sand ridges have composite nature being formed by several superimposed secondary ridges.
基金supported by a University of East London Excellence PhD scholarship to MT and in part from a Medical Research Council grant to CF(grant number G0802594).
文摘Background:Motor adaptation relies on error-based learning for accurate movements in changing environ-ments.However,the neurophysiological mechanisms driving individual differences in performance are unclear.Transcranial magnetic stimulation(TMS)-evoked potential can provide a direct measure of cortical excitability.Objective:To investigate cortical excitability as a predictor of motor learning and motor adaptation in a robot-mediated forcefield.Methods:A group of 15 right-handed healthy participants(mean age 23 years)performed a robot-mediated forcefield perturbation task.There were two conditions:unperturbed non-adaptation and perturbed adapta-tion.TMS was applied in the resting state at baseline and following motor adaptation over the contralateral primary motor cortex(left M1).Electroencephalographic(EEG)activity was continuously recorded,and cortical excitability was measured by TMS-evoked potential(TEP).Motor learning was quantified by the motor learning index.Results:Larger error-related negativity(ERN)in fronto-central regions was associated with improved motor per-formance as measured by a reduction in trajectory errors.Baseline TEP N100 peak amplitude predicted motor learning(P=0.005),which was significantly attenuated relative to baseline(P=0.0018)following motor adap-tation.Conclusions:ERN reflected the formation of a predictive internal model adapted to the forcefield perturbation.Attenuation in TEP N100 amplitude reflected an increase in cortical excitability with motor adaptation reflecting neuroplastic changes in the sensorimotor cortex.TEP N100 is a potential biomarker for predicting the outcome in robot-mediated therapy and a mechanism to investigate psychomotor abnormalities in depression.
