The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence ...The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.展开更多
Under bilateral cooperation between the United States of America and the People's Republic of China, a series of research cruises were conducted over the western Pacific Ocean. It was found that a) the non-sea-sal...Under bilateral cooperation between the United States of America and the People's Republic of China, a series of research cruises were conducted over the western Pacific Ocean. It was found that a) the non-sea-salt sulfate aerosol particles are the major source of cloud condensation nuclei, b) the population of clouds and the total albedo are proportional to the concentration of condensation nuclei and consequently to the concentration of the non-sea-salt aerosol particles, and c) the amount of rainfall is inversely proportional to the concentration of non-sea-salt sulfate aerosol particles. It seems that anthropogenic sulfate aerosol particles affect the regional planetary albedo and climate and that the contribution from biogenically derived sulfate aerosol particles is of lesser importance.展开更多
The renal handling of Na^(+) balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the...The renal handling of Na^(+) balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^(+) excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. G-protein coupled receptors(GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na^(+) absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na^(+) excretion, this review also highlights the complexity of these different pathways, and the connections between them.展开更多
Objective:To evaluate the potential prophylactic activity of traditional polyherbal remedy against malaria.Methods:A traditional polyherbal remedy against malaria from Odisha,India was evaluated for its potential prop...Objective:To evaluate the potential prophylactic activity of traditional polyherbal remedy against malaria.Methods:A traditional polyherbal remedy against malaria from Odisha,India was evaluated for its potential prophylactic activity using in vitro hepatic cell lines assay and the murine malaria system Plasmodium yoelii yoelii/Anopheles stephensi.Results:The polyherbal extract inhibited the Plasmodium yoelii hepatic stages in vitro(IC500.74 mg/m L),a therapeutic index of 9.54.In mice treated with the aqueous extract(2 000 mg/kg/day),peak parasitaemia values were 81%lower in the experimental2.35%±0.14%as compared to controls 12.62%±0.52%(P<0.001),suggesting significant prophylactic activity.Conclusions:The observations provide a proof of concept for a traditional malaria prophylactic remedy used by tribal populations in India.展开更多
AIM:To develop and validate a transient micro-elastography device to measure liver stiffness(LS) in mice.METHODS:A novel transient micro-elastography(TME) device,dedicated to LS measurements in mice with a range of me...AIM:To develop and validate a transient micro-elastography device to measure liver stiffness(LS) in mice.METHODS:A novel transient micro-elastography(TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston.The novel probe was validated in a classical fibrosis model(CCl4) and in a transgenic murine model of systemic amyloidosis.RESULTS:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement(0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls(18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover,fibrosis stage was highly correlated with LS(Spearman coefficient = 0.88,P < 0.01).In the amyloidosis model,much higher LS values were obtained,reaching maximum values of > 150 kPa.LS significantly correlated with the amyloidosis index(0.93,P < 0.0001) and the plasma concentration of mutant hapoA-□(0.62,P < 0.005).CONCLUSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS.展开更多
Autophagy is invoIved in spermatogenesis by regulating germ cell maturation.This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles.Cryptorchidism is associated ...Autophagy is invoIved in spermatogenesis by regulating germ cell maturation.This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles.Cryptorchidism is associated with impairment of germ cell maturation revealed by the presence of immature forms of sperm cells in ejaculates.The aim of the present study was to evaluate the status of autophagy in sperm cells from cryptorchid patients.Semen samples of cryptorchid patients and normozoospermic controls were analyzed by immuno cytochemistry and electron microscopy.Autophagy protei ns,autophagy-related protein 9(ATG9)and microtubule-associated protein,lA/lB-light chain 3(LC3)were localized by immunocytochemistry on the acrosome and on the equatorial segment of sperm cells.LC3 was also detected in the midpiece of cryptorchid sperm tail.Autophagy substrate p62 protein was present in the acrosome and in the postequatorial segment of sperm in control samples,but not in the cryptorchid ones.Transmission electron microscopy revealed double-membrane-limited autophagosomes in postequatorial part of spermatozoa head and midpiece in cryptorchid samples.Partly degraded mitochondria were frequently discerned in autophagic vacuoles.In conclusion,autophagy is increased in sperm cells from patients with cryptorchid history comparatively to control.Our work provides insights into the role of autophagy in the maturation and survival of human male gametes in pathological conditions.Thus,regulating autophagy could represent a potential way to improve sperm quality in cryptorchid men.展开更多
This paper analyzed the variations of latent heat flux (LHF) over the tropical Pacific in the period 1978-1988 by using COADS (Comprehensive Ocean and Atmospheric Data Set). It has been founded that the interannual va...This paper analyzed the variations of latent heat flux (LHF) over the tropical Pacific in the period 1978-1988 by using COADS (Comprehensive Ocean and Atmospheric Data Set). It has been founded that the interannual variabili ty of LHF exhibits strong ENSO signal, with the significant increasing LHF during the recent two warm events, i.e., 1982 / 83 and 1986 / 87 and decreasing LHF in the cold episodes. However the longitudinal distribution of the LHF departures varies from event to event. In the eastern Pacific, the specific humidity difference at air-sea interface (qs -qa) makes a dominant contribution to the interannual variability of LHF ( r = 0.73 ), while in the western Pacific the surface wind speed, W and the qs - qa make nearly equal contribution to that of LHF.展开更多
To investigate the life cycle of marine sulfate aerosols, chemicophysical characteristics of marine aerosolswere measured during five cruises in the Pacific Ocean. Dimethyl sulfide concentrations in seawater and in th...To investigate the life cycle of marine sulfate aerosols, chemicophysical characteristics of marine aerosolswere measured during five cruises in the Pacific Ocean. Dimethyl sulfide concentrations in seawater and in the air were also measured. The geographic variation of sulfate-aerosol concentrations was studied in relation to biogenic and anthropogenic sources,transport with air trajectories, and chemical transformations in the atmosphere. The highest concentrations were found near Asian and American ports, indicating anthropogenic pollution is the major sulfate aerosols source. Higher concentrations were observed in the upwelling regions than in the oligotrophic areas. Along the coastal regions, both mass and number concentrations of sulfate aerosols depended on wind direction and wind speed, and land-breeze and sea-breeze oscillations; no clear diurnal variation was detected. In pelagic areas, along the equator, the concentrations of small sulfate particles showed a maximum in the afternoon and the minimum at night , indicating photo-oxidation as an important process for gas-to-particle conversion. Higher sulfate-aerosol concentrations were observed in spring than in autumn and higher concentrations were found during the La Nina anomaly than during the El Nino anomaly. Biogenic source of sulfate aerosols has an important role in the remote ocean. Case studies of sulfate-aerosol distributions are discussed.展开更多
A novel latent thermal initiator, ferricenium tetrafluoroborate salt (FcBF4), for cationic polymerization of epoxides is reported. The activities of FcBF4 for different epoxides, including bisphenol-A-type epoxy oligo...A novel latent thermal initiator, ferricenium tetrafluoroborate salt (FcBF4), for cationic polymerization of epoxides is reported. The activities of FcBF4 for different epoxides, including bisphenol-A-type epoxy oligomer E44, cycloaliphatic epoxy ERL4221, and glycidylether epoxy GGE, were evaluated by differential scanning calorimetry (DSC). The results showed a moderate thermal initiation activity for E44 and GGE at 78℃ and 108℃ respectively. When adding GGE to E44, the reaction was enhanced. The temperature of thermal degradation of the cured specimens for the system of E44/FcBF4, E44+10%GGE/FcBF4 and E44+10%ERL4221/FcBF4 is higher than 350℃.展开更多
Hepcidin is the hyposideremic hormone regulating iron metabolism.It is a defensin-like disulfide-bonded peptide with antimicrobial activity.The main site of hepcidin production is the liver where its synthesis is modu...Hepcidin is the hyposideremic hormone regulating iron metabolism.It is a defensin-like disulfide-bonded peptide with antimicrobial activity.The main site of hepcidin production is the liver where its synthesis is modulated by iron,inflammation and erythropoietic signaling.However,hepcidin locally produced in several peripheral organs seems to be an important actor for the maintenance of iron homeostasis in these organs.This review highlights the presence of peripheral hepcidin and its potential functions.Understanding the role of extrahepatic hepcidin could be of great physiological and therapeutic importance for several specific pathologies.展开更多
文摘The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.
文摘Under bilateral cooperation between the United States of America and the People's Republic of China, a series of research cruises were conducted over the western Pacific Ocean. It was found that a) the non-sea-salt sulfate aerosol particles are the major source of cloud condensation nuclei, b) the population of clouds and the total albedo are proportional to the concentration of condensation nuclei and consequently to the concentration of the non-sea-salt aerosol particles, and c) the amount of rainfall is inversely proportional to the concentration of non-sea-salt sulfate aerosol particles. It seems that anthropogenic sulfate aerosol particles affect the regional planetary albedo and climate and that the contribution from biogenically derived sulfate aerosol particles is of lesser importance.
文摘The renal handling of Na^(+) balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^(+) excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. G-protein coupled receptors(GPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel GPCR-dependent regulatory systems that have been shown to modulate renal Na^(+) absorption in the distal nephron. In addition to the multiplicity of the GPCR that regulate Na^(+) excretion, this review also highlights the complexity of these different pathways, and the connections between them.
基金Aquarius Group of Companies,SingaporeETC CAPTURED Programme,the Netherlands(Grant No.DGIS/D)
文摘Objective:To evaluate the potential prophylactic activity of traditional polyherbal remedy against malaria.Methods:A traditional polyherbal remedy against malaria from Odisha,India was evaluated for its potential prophylactic activity using in vitro hepatic cell lines assay and the murine malaria system Plasmodium yoelii yoelii/Anopheles stephensi.Results:The polyherbal extract inhibited the Plasmodium yoelii hepatic stages in vitro(IC500.74 mg/m L),a therapeutic index of 9.54.In mice treated with the aqueous extract(2 000 mg/kg/day),peak parasitaemia values were 81%lower in the experimental2.35%±0.14%as compared to controls 12.62%±0.52%(P<0.001),suggesting significant prophylactic activity.Conclusions:The observations provide a proof of concept for a traditional malaria prophylactic remedy used by tribal populations in India.
文摘AIM:To develop and validate a transient micro-elastography device to measure liver stiffness(LS) in mice.METHODS:A novel transient micro-elastography(TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston.The novel probe was validated in a classical fibrosis model(CCl4) and in a transgenic murine model of systemic amyloidosis.RESULTS:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement(0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls(18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover,fibrosis stage was highly correlated with LS(Spearman coefficient = 0.88,P < 0.01).In the amyloidosis model,much higher LS values were obtained,reaching maximum values of > 150 kPa.LS significantly correlated with the amyloidosis index(0.93,P < 0.0001) and the plasma concentration of mutant hapoA-□(0.62,P < 0.005).CONCLUSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS.
文摘Autophagy is invoIved in spermatogenesis by regulating germ cell maturation.This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles.Cryptorchidism is associated with impairment of germ cell maturation revealed by the presence of immature forms of sperm cells in ejaculates.The aim of the present study was to evaluate the status of autophagy in sperm cells from cryptorchid patients.Semen samples of cryptorchid patients and normozoospermic controls were analyzed by immuno cytochemistry and electron microscopy.Autophagy protei ns,autophagy-related protein 9(ATG9)and microtubule-associated protein,lA/lB-light chain 3(LC3)were localized by immunocytochemistry on the acrosome and on the equatorial segment of sperm cells.LC3 was also detected in the midpiece of cryptorchid sperm tail.Autophagy substrate p62 protein was present in the acrosome and in the postequatorial segment of sperm in control samples,but not in the cryptorchid ones.Transmission electron microscopy revealed double-membrane-limited autophagosomes in postequatorial part of spermatozoa head and midpiece in cryptorchid samples.Partly degraded mitochondria were frequently discerned in autophagic vacuoles.In conclusion,autophagy is increased in sperm cells from patients with cryptorchid history comparatively to control.Our work provides insights into the role of autophagy in the maturation and survival of human male gametes in pathological conditions.Thus,regulating autophagy could represent a potential way to improve sperm quality in cryptorchid men.
文摘This paper analyzed the variations of latent heat flux (LHF) over the tropical Pacific in the period 1978-1988 by using COADS (Comprehensive Ocean and Atmospheric Data Set). It has been founded that the interannual variabili ty of LHF exhibits strong ENSO signal, with the significant increasing LHF during the recent two warm events, i.e., 1982 / 83 and 1986 / 87 and decreasing LHF in the cold episodes. However the longitudinal distribution of the LHF departures varies from event to event. In the eastern Pacific, the specific humidity difference at air-sea interface (qs -qa) makes a dominant contribution to the interannual variability of LHF ( r = 0.73 ), while in the western Pacific the surface wind speed, W and the qs - qa make nearly equal contribution to that of LHF.
文摘To investigate the life cycle of marine sulfate aerosols, chemicophysical characteristics of marine aerosolswere measured during five cruises in the Pacific Ocean. Dimethyl sulfide concentrations in seawater and in the air were also measured. The geographic variation of sulfate-aerosol concentrations was studied in relation to biogenic and anthropogenic sources,transport with air trajectories, and chemical transformations in the atmosphere. The highest concentrations were found near Asian and American ports, indicating anthropogenic pollution is the major sulfate aerosols source. Higher concentrations were observed in the upwelling regions than in the oligotrophic areas. Along the coastal regions, both mass and number concentrations of sulfate aerosols depended on wind direction and wind speed, and land-breeze and sea-breeze oscillations; no clear diurnal variation was detected. In pelagic areas, along the equator, the concentrations of small sulfate particles showed a maximum in the afternoon and the minimum at night , indicating photo-oxidation as an important process for gas-to-particle conversion. Higher sulfate-aerosol concentrations were observed in spring than in autumn and higher concentrations were found during the La Nina anomaly than during the El Nino anomaly. Biogenic source of sulfate aerosols has an important role in the remote ocean. Case studies of sulfate-aerosol distributions are discussed.
文摘A novel latent thermal initiator, ferricenium tetrafluoroborate salt (FcBF4), for cationic polymerization of epoxides is reported. The activities of FcBF4 for different epoxides, including bisphenol-A-type epoxy oligomer E44, cycloaliphatic epoxy ERL4221, and glycidylether epoxy GGE, were evaluated by differential scanning calorimetry (DSC). The results showed a moderate thermal initiation activity for E44 and GGE at 78℃ and 108℃ respectively. When adding GGE to E44, the reaction was enhanced. The temperature of thermal degradation of the cured specimens for the system of E44/FcBF4, E44+10%GGE/FcBF4 and E44+10%ERL4221/FcBF4 is higher than 350℃.
文摘Hepcidin is the hyposideremic hormone regulating iron metabolism.It is a defensin-like disulfide-bonded peptide with antimicrobial activity.The main site of hepcidin production is the liver where its synthesis is modulated by iron,inflammation and erythropoietic signaling.However,hepcidin locally produced in several peripheral organs seems to be an important actor for the maintenance of iron homeostasis in these organs.This review highlights the presence of peripheral hepcidin and its potential functions.Understanding the role of extrahepatic hepcidin could be of great physiological and therapeutic importance for several specific pathologies.
