Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiolo...Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite(ONOO-) is formed solely in the presence of superoxide anion(O2-). Neopterin and kynurenine to tryptophan ratio(Kyn/Trp),as an estimate of IDO enzyme activity,are robust markers of immune activation in vitro and in vivo. Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise,a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C,-E and-B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites,BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD.展开更多
Studies of receptor-mediated lipoprotein metabolic pathways in avian species have revealed that physiological intricacies of specific cell types are highly analogous to those in mammals. A prime example for the power ...Studies of receptor-mediated lipoprotein metabolic pathways in avian species have revealed that physiological intricacies of specific cell types are highly analogous to those in mammals. A prime example for the power of com- parative studies across different animal kingdoms, elucidated in the chicken, is that the expression of different lipo- protein receptors in somatic cells and oocytes are the key to oocyte growth. In avian species, yolk precursor transport from the hen＇s liver to rapidly growing oocytes and the subsequent transfer of yolk nutrients via the yolk sac to the developing embryo are highly efficient processes. Oocytes grow from a diameter of 5 mm to 2.5-3 cm in only 7 days, and the yolk sac transfers nutrients from the yolk stored in the mature oocyte to the embryo within just 2 weeks. The underlying key transport mechanism is receptor-mediated endocytosis of macromolecules, i.e., of hepatically synthesized yolk precursors for oocyte growth, and of mature yolk components for embryo nutrition, respectively. Recently, the receptors involved, as well as the role of lipoprotein synthesis in the yolk sac have been identified. As outlined here, lipoprotein degradation/resynthesis cycles and the expression of lipoprotein receptors are not only coordinated with the establishment of the tbllicular architecture embedding the oocyte, but also with the generation of the yolk sac vasculature essential for nutrient transfer to the embryo.展开更多
Localized cell wall thickenings, so called papillae, are a common plant defense response to fungal attack at sites of penetration of the plant cell. The major constituent of papillae is callose, a (1,3)-β-glucan poly...Localized cell wall thickenings, so called papillae, are a common plant defense response to fungal attack at sites of penetration of the plant cell. The major constituent of papillae is callose, a (1,3)-β-glucan polymer, which contributes to slowing or blocking the invading fungal hyphae. In the model plant Arabidopsis thaliana, we could recently show that the overexpression of PMR4(POWDERY MILDEW RESITANT 4), which encodes a stress induced callose synthase, results in complete powdery mildew resistance. To evaluate if these findings are also transferable to monocot crops, we transiently expressed PMR4 under control of the 35S promoter in leaves of barley (Hordeum vulgare) seedlings, which were subsequently inoculated with the virulent powdery mildew Blumeria graminis f. sp. hordei. Fusion of the green fluorescent protein (GFP) to PMR4 allowed the identification of successfully transformed barley cells, which showed an increased penetration resistance to B. graminis compared to control cells that express only GFP.PMR4-GFP localized in a similar pattern at the site of attempted fungal penetration as observed inA. thaliana, which suggests that similar transport mechanisms of the callose synthase might exist in dicot and monocot plants.展开更多
Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to si...Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.展开更多
An important indicator of the rangeland health, associated with land degradation, is the ability of semi-natural rangelands to provide forage of sufficient quality for livestock production. In Qilian Mountains(Gansu P...An important indicator of the rangeland health, associated with land degradation, is the ability of semi-natural rangelands to provide forage of sufficient quality for livestock production. In Qilian Mountains(Gansu Province, NW China) biomass production and forage quality are dependent on the seasonality of precipitation and temperature; most of the precipitation falls during summer season, when sheep, goats and yaks graze mountain rangelands. To sustain the rangelands and to improve the management strategies, the assessment of the forage quality should be implemented. The purpose of this research was to study the response of biomass, forage quality and macronutrient content different levels of grazing intensity in Qilian rangelands. We sampled aboveground biomass in the growing seasons in 2012 and 2013 within spring/autumn or summer grazing regimes in two altitudinal zones below and above 3000 m a.s.l.(montane-subalpine and subalpine-alpine respectively). In order to estimate forage quality, biomass was sampled in 1 m × 1 m plots, assigned to the center of 10 ×10 m sites, fromwhich we collected different indicator parameters of rangeland health. Mineral and fiber content of forage biomass was estimated under different levels of grazing intensity with regard to the growing period. It was found that an increase in grazing intensity led to a decrease in dry matter weight. No linearity was observed in the relationship between nutritive value and grazing intensity. The highest fiber content(59.20 %) was found in plots mostly disturbed by grazing. The highest protein(16.30 %) and the lowest fiber(51.30 %) contents were associated with slightly grazing intensity. Concentrations of the mineral elements, such as Zn, P, K and S varied significantly and showed maximum values under low grazing intensity.展开更多
Sphenomorphus incognitus is recorded for the first time outside of China. The new locality record is from the Tay Yen Tu Nature Reserve in Bac Giang Province, northeastern Vietnam at elevations between 200–450 m. Bas...Sphenomorphus incognitus is recorded for the first time outside of China. The new locality record is from the Tay Yen Tu Nature Reserve in Bac Giang Province, northeastern Vietnam at elevations between 200–450 m. Based on the newly collected specimens, we present an expanded description and provide data on the natural history of this species in northern Vietnam.展开更多
Objectives: To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol con centrations predict the response. Study design: We perform...Objectives: To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol con centrations predict the response. Study design: We performed a randomized, place bo-controlled trial on infants with gestation ≤30 weeks, body weight of 501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly befor e hydrocortisone treatment, basal and stimulated (ACTH, 0.1 μg/kg) serum cortis ols were measured. Results: The study was discontinued early, because of gastroi ntestinal perforations in the hydrocortisone group (4/25 vs 0/26, P =. 05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of BPD (28%vs placebo 42%, P = 0.28) tended to be lower, and patent ductus arteriosus (36%vs 73%, P =. 01)was lower in the hydrocortisone group. The hydrocortisone-treated infan ts with serum cortisol concentrations above the median had a high risk of gastro intestinal perforation. In infants with cortisol values below the median, hydroc ortisone treatment increased survival without BPD. Conclusions: Serum cortisol c oncentrations measured shortly after birth may identify those very high-risk in fants who may benefit from hydrocortisone supplementation.展开更多
Heat stress proteins (Hsp) and heat stress transcription factors (Hsf) are structurally and functionally conserved elements of the eukaryotic heat stress response. However, compared to other organisms, plants have muc...Heat stress proteins (Hsp) and heat stress transcription factors (Hsf) are structurally and functionally conserved elements of the eukaryotic heat stress response. However, compared to other organisms, plants have much more elaborate systems of chaperones and at least 21 transcription factors controlling their expression.展开更多
AIM： To characterise the effect of energy restriction （ER） on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further e...AIM： To characterise the effect of energy restriction （ER） on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium. METHODS： Liver metabolomic profile of lean and obese C57BI/6J mice （n = 10/group） were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet （whey ＋ Ca）. The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS： ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey ＋ Ca diet significantly decreased blood glucose （P 〈 0.001） and serum insulin （P 〈 0.01）. In hepatic lipid species the biggest reduction was in the level of triacylglycerols and cerarnides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey ＋ Ca ER group （P 〈 0.001, vs obese）. ER on whey ＋ Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic cerarnides （P 〈 0.001, vs obese; P 〉 0.05, vs lean）. These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway rnetabolites. CONCLUSION： ER-induced changes on hepatic rnetabolornic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.展开更多
Thirty-nine rhizobial isolates were isolated from the root nodules of Glycyrrhiza uralensis and Glyeyrrhiza glabra, growing in the arid and semiarid regions of northwestern China, to test their taxonomic position and ...Thirty-nine rhizobial isolates were isolated from the root nodules of Glycyrrhiza uralensis and Glyeyrrhiza glabra, growing in the arid and semiarid regions of northwestern China, to test their taxonomic position and stress tolerance and to select one promising putative inoeulant strain for further studies. On the basis of 113 physiological and biochemical characteristics, the isolates were clustered into three groups. One isolate CCNWGX035 was found to have high tolerance to NaC1, pH, and temperature. By sequencing the 16S rDNA, isolate CCNWGX035 was placed in genus Mesorhizobium. Nodulation tests demonstrated that the isolate not only formed nitrogen-fixing nodules on its original host plant Glyeyrrhiza glabra, but also on Sophora vieiifolia, Lotus cornieulatus, Trifolium repens, Melilotus suaveolens, and Sophora alopecuroides. On the basis of sequence analysis of the nodA gene, isolate CCNWGX035 was closely related to strains of the genus Mesorhizobium, exhibiting some novel characteristics of root nodule bacteria.展开更多
Prostate cancer(PCa)is the second leading cause of death among men worldwide.Androgen signaling plays key roles in PCa progression[1],and so far available therapeutic agents mainly target androgens or androgen recepto...Prostate cancer(PCa)is the second leading cause of death among men worldwide.Androgen signaling plays key roles in PCa progression[1],and so far available therapeutic agents mainly target androgens or androgen receptor(AR)[2].However,the patients receiving these treatments often recurs with progression to castration resistant prostate cancer(CRPC)[3].Metastatic CRPC(mCRPC)is the advanced and lethal stage of PCa[4].Recent advances in the field show that immune checkpoint blockade(ICB)is the paramount choice for targeting many types of cancers including PCa[4e6].ICB generates effective therapeutic response across certain cancers[5],whereas it failed to improve overall survival of patients with mCRPC[7].To address this challenge,one recent study by Lu and colleagues[8]has demonstrated an ICB approach combined with targeted drugs for myeloid-derived immune suppressive cells(MDSCs),thereby enforcing the T cells to combat mCRPC tumor cells[8].展开更多
The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member ...The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uP AR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasivecarcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.展开更多
Seabuckthorn (Hippophae rhamnoides L.) is a dioecious plant with berries containing high amounts of several bioactive compounds with nutritional and medicinal traits. It is also planted to control soil erosion. A gene...Seabuckthorn (Hippophae rhamnoides L.) is a dioecious plant with berries containing high amounts of several bioactive compounds with nutritional and medicinal traits. It is also planted to control soil erosion. A genetic transformation procedure will facilitate studies of the control of plant development and interactions with symbionts and pathogens, and will provide a tool for plant breeding. Here, we present a particle bombardment method for transforming seabuckthorn. The early stages of induced adventitious shoots from roots were chosen as a novel target tissue for the transformation procedure. The root system was bombarded with gold particles coated with plasmid pRT99gus containing genes for plant kanamycin resistance and for β-glucuronidase expression, and shoots were regenerated under kanamycin selection. PCR analysis of the regenerated transformed lines confirmed the presence of a 603 bp gus (uidA) gene fragment and a 1.5 kb fragment from the 35S promoter in three shoots from independent transformation events.展开更多
Despite tremendous progress made in human prostate biology over the past few decades,a full picture of prostate lineage hierarchy and its connection to cancer initiation remain to be delineated.Two recent studies publ...Despite tremendous progress made in human prostate biology over the past few decades,a full picture of prostate lineage hierarchy and its connection to cancer initiation remain to be delineated.Two recent studies published in Nat Genet.[1]and in Science[2]have profiled subpopulations of prostate cells at the single-cell level.Complementary analyses of data from the studies demonstrate self-renewal and differentiation capacities of different luminal epithelial cells,which can serve as cells of origin for prostate cancer.The system of lineage hierarchy controls cell differentiation and tissue formation from stem and progenitor cells,which may initiate cancer development if the process goes awry[3].Therefore,it is of great interest to identify cells with stemness or progenitor properties and delineate their lineage hierarchy in order to pinpoint the cells of origin for cancer when cellular genetics are altered[4].展开更多
Astrocytes are implicated in the neuropathology of Alzheimer’s disease (AD) by clustering with other activated inflammatory cells at the sites of amyloid beta (Aβ) deposits formed in the cortex and hippocampus. Astr...Astrocytes are implicated in the neuropathology of Alzheimer’s disease (AD) by clustering with other activated inflammatory cells at the sites of amyloid beta (Aβ) deposits formed in the cortex and hippocampus. Astrocytes are known to contribute to the clearance of Aβ in the AD brain. Also, adult but not neonatal mouse astrocytes are able to clear Aβ deposits from the tissue sections of transgenic AD mice and human brain ex vivo. Because these findings suggest that cultured neonatal astrocytes may not represent a relevant cell for modeling the function of astrocytes in neurodegenerative diseases, we studied whether neonatal and adult astrocytes show different responses in gene expression when exposed to brain sections burdened by deposits of human Aβ. Whole genome microbarrays demonstrated greater alteration of gene expression in adult astrocytes than in neonatal astrocytes. When exposed to Aβ burdened brain sections adult but not neonatal astrocytes up-regulated genes related to peptidase (such as MMP13, MMP12, Phex, Htra1), scavenger receptor (Scara5, Enpp2) and glutathioine transferase (Gsta1, Gsta2, Gclm) activity, suggesting increased ability to degrade and endocytose Aβ peptides and protect against oxidative bursts. Quantitative RT-PCR analysis confirmed the significant alteration in gene expression of key peptidases, scavenger receptors and cholesterol synthesis. Our data suggest that adult astrocytes in culture are more sensitive to disease-relevant stress showing more extensive genetic response compared to neonatal astrocytes. In addition, the identified peptidases and scavenger receptors which increase expression selectively in adult astrocytes suggest their major role in astrocyte-mediated clearance of Aβ deposits in AD.展开更多
文摘Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite(ONOO-) is formed solely in the presence of superoxide anion(O2-). Neopterin and kynurenine to tryptophan ratio(Kyn/Trp),as an estimate of IDO enzyme activity,are robust markers of immune activation in vitro and in vivo. Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise,a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C,-E and-B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites,BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD.
基金supported by Research Grants from the Austrian Science Fundthe Austrian National Bankthe Herzfelder Family Endowment
文摘Studies of receptor-mediated lipoprotein metabolic pathways in avian species have revealed that physiological intricacies of specific cell types are highly analogous to those in mammals. A prime example for the power of com- parative studies across different animal kingdoms, elucidated in the chicken, is that the expression of different lipo- protein receptors in somatic cells and oocytes are the key to oocyte growth. In avian species, yolk precursor transport from the hen＇s liver to rapidly growing oocytes and the subsequent transfer of yolk nutrients via the yolk sac to the developing embryo are highly efficient processes. Oocytes grow from a diameter of 5 mm to 2.5-3 cm in only 7 days, and the yolk sac transfers nutrients from the yolk stored in the mature oocyte to the embryo within just 2 weeks. The underlying key transport mechanism is receptor-mediated endocytosis of macromolecules, i.e., of hepatically synthesized yolk precursors for oocyte growth, and of mature yolk components for embryo nutrition, respectively. Recently, the receptors involved, as well as the role of lipoprotein synthesis in the yolk sac have been identified. As outlined here, lipoprotein degradation/resynthesis cycles and the expression of lipoprotein receptors are not only coordinated with the establishment of the tbllicular architecture embedding the oocyte, but also with the generation of the yolk sac vasculature essential for nutrient transfer to the embryo.
文摘Localized cell wall thickenings, so called papillae, are a common plant defense response to fungal attack at sites of penetration of the plant cell. The major constituent of papillae is callose, a (1,3)-β-glucan polymer, which contributes to slowing or blocking the invading fungal hyphae. In the model plant Arabidopsis thaliana, we could recently show that the overexpression of PMR4(POWDERY MILDEW RESITANT 4), which encodes a stress induced callose synthase, results in complete powdery mildew resistance. To evaluate if these findings are also transferable to monocot crops, we transiently expressed PMR4 under control of the 35S promoter in leaves of barley (Hordeum vulgare) seedlings, which were subsequently inoculated with the virulent powdery mildew Blumeria graminis f. sp. hordei. Fusion of the green fluorescent protein (GFP) to PMR4 allowed the identification of successfully transformed barley cells, which showed an increased penetration resistance to B. graminis compared to control cells that express only GFP.PMR4-GFP localized in a similar pattern at the site of attempted fungal penetration as observed inA. thaliana, which suggests that similar transport mechanisms of the callose synthase might exist in dicot and monocot plants.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2015RIDIAIA01059432)
文摘Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.
基金the Robert Bosch Foundation (No.070610) for financial support of this joint international projectFinancial support of the PhD research project was provided by University of Hamburg’s Doctoral Funding Program (HmbNFG)merit scholarship program
文摘An important indicator of the rangeland health, associated with land degradation, is the ability of semi-natural rangelands to provide forage of sufficient quality for livestock production. In Qilian Mountains(Gansu Province, NW China) biomass production and forage quality are dependent on the seasonality of precipitation and temperature; most of the precipitation falls during summer season, when sheep, goats and yaks graze mountain rangelands. To sustain the rangelands and to improve the management strategies, the assessment of the forage quality should be implemented. The purpose of this research was to study the response of biomass, forage quality and macronutrient content different levels of grazing intensity in Qilian rangelands. We sampled aboveground biomass in the growing seasons in 2012 and 2013 within spring/autumn or summer grazing regimes in two altitudinal zones below and above 3000 m a.s.l.(montane-subalpine and subalpine-alpine respectively). In order to estimate forage quality, biomass was sampled in 1 m × 1 m plots, assigned to the center of 10 ×10 m sites, fromwhich we collected different indicator parameters of rangeland health. Mineral and fiber content of forage biomass was estimated under different levels of grazing intensity with regard to the growing period. It was found that an increase in grazing intensity led to a decrease in dry matter weight. No linearity was observed in the relationship between nutritive value and grazing intensity. The highest fiber content(59.20 %) was found in plots mostly disturbed by grazing. The highest protein(16.30 %) and the lowest fiber(51.30 %) contents were associated with slightly grazing intensity. Concentrations of the mineral elements, such as Zn, P, K and S varied significantly and showed maximum values under low grazing intensity.
基金Vietnam was partially funded by IEBR(Vietnam)+4 种基金the Nagao Natural Environment Foundation(Japan)the German Academic Exchange Service(DAAD)Research of T.Q.Nguyen in Germany is funded by the Alexander von Humboldt Foundation(VIE 1143441 STP)
文摘Sphenomorphus incognitus is recorded for the first time outside of China. The new locality record is from the Tay Yen Tu Nature Reserve in Bac Giang Province, northeastern Vietnam at elevations between 200–450 m. Based on the newly collected specimens, we present an expanded description and provide data on the natural history of this species in northern Vietnam.
文摘Objectives: To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol con centrations predict the response. Study design: We performed a randomized, place bo-controlled trial on infants with gestation ≤30 weeks, body weight of 501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly befor e hydrocortisone treatment, basal and stimulated (ACTH, 0.1 μg/kg) serum cortis ols were measured. Results: The study was discontinued early, because of gastroi ntestinal perforations in the hydrocortisone group (4/25 vs 0/26, P =. 05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of BPD (28%vs placebo 42%, P = 0.28) tended to be lower, and patent ductus arteriosus (36%vs 73%, P =. 01)was lower in the hydrocortisone group. The hydrocortisone-treated infan ts with serum cortisol concentrations above the median had a high risk of gastro intestinal perforation. In infants with cortisol values below the median, hydroc ortisone treatment increased survival without BPD. Conclusions: Serum cortisol c oncentrations measured shortly after birth may identify those very high-risk in fants who may benefit from hydrocortisone supplementation.
文摘Heat stress proteins (Hsp) and heat stress transcription factors (Hsf) are structurally and functionally conserved elements of the eukaryotic heat stress response. However, compared to other organisms, plants have much more elaborate systems of chaperones and at least 21 transcription factors controlling their expression.
基金Foundation for Nutrition Research, Academy of Finland, Sigrid Juselius Foundation and Valio Ltd., Helsinki, Finland
文摘AIM： To characterise the effect of energy restriction （ER） on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium. METHODS： Liver metabolomic profile of lean and obese C57BI/6J mice （n = 10/group） were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet （whey ＋ Ca）. The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS： ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey ＋ Ca diet significantly decreased blood glucose （P 〈 0.001） and serum insulin （P 〈 0.01）. In hepatic lipid species the biggest reduction was in the level of triacylglycerols and cerarnides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey ＋ Ca ER group （P 〈 0.001, vs obese）. ER on whey ＋ Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic cerarnides （P 〈 0.001, vs obese; P 〉 0.05, vs lean）. These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway rnetabolites. CONCLUSION： ER-induced changes on hepatic rnetabolornic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.
基金Project supported by the Program for the New Century Excellent Talents in University of China (No.NCET-04-0953)the Fund of Author of Chinese Excellent Doctor Degree Dissertation (No.200254)the National Natural Science Foundation of China (Nos.30470040 and 30670372).
文摘Thirty-nine rhizobial isolates were isolated from the root nodules of Glycyrrhiza uralensis and Glyeyrrhiza glabra, growing in the arid and semiarid regions of northwestern China, to test their taxonomic position and stress tolerance and to select one promising putative inoeulant strain for further studies. On the basis of 113 physiological and biochemical characteristics, the isolates were clustered into three groups. One isolate CCNWGX035 was found to have high tolerance to NaC1, pH, and temperature. By sequencing the 16S rDNA, isolate CCNWGX035 was placed in genus Mesorhizobium. Nodulation tests demonstrated that the isolate not only formed nitrogen-fixing nodules on its original host plant Glyeyrrhiza glabra, but also on Sophora vieiifolia, Lotus cornieulatus, Trifolium repens, Melilotus suaveolens, and Sophora alopecuroides. On the basis of sequence analysis of the nodA gene, isolate CCNWGX035 was closely related to strains of the genus Mesorhizobium, exhibiting some novel characteristics of root nodule bacteria.
文摘Prostate cancer(PCa)is the second leading cause of death among men worldwide.Androgen signaling plays key roles in PCa progression[1],and so far available therapeutic agents mainly target androgens or androgen receptor(AR)[2].However,the patients receiving these treatments often recurs with progression to castration resistant prostate cancer(CRPC)[3].Metastatic CRPC(mCRPC)is the advanced and lethal stage of PCa[4].Recent advances in the field show that immune checkpoint blockade(ICB)is the paramount choice for targeting many types of cancers including PCa[4e6].ICB generates effective therapeutic response across certain cancers[5],whereas it failed to improve overall survival of patients with mCRPC[7].To address this challenge,one recent study by Lu and colleagues[8]has demonstrated an ICB approach combined with targeted drugs for myeloid-derived immune suppressive cells(MDSCs),thereby enforcing the T cells to combat mCRPC tumor cells[8].
基金Supported by Copenhagen University Hospital(Rigshospitalets Forskningspuljer)The Danish National Research Foundation(Danish-Chinese Centre for Proteases and Cancer)Harboefonden,Torben og Alice Frimodts Fond,Fabrikant Einar Willumsens Mindelegat,Holger Rabitz and hustrus Legat,The Lundbeck Foundation.
文摘The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uP AR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasivecarcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.
文摘Seabuckthorn (Hippophae rhamnoides L.) is a dioecious plant with berries containing high amounts of several bioactive compounds with nutritional and medicinal traits. It is also planted to control soil erosion. A genetic transformation procedure will facilitate studies of the control of plant development and interactions with symbionts and pathogens, and will provide a tool for plant breeding. Here, we present a particle bombardment method for transforming seabuckthorn. The early stages of induced adventitious shoots from roots were chosen as a novel target tissue for the transformation procedure. The root system was bombarded with gold particles coated with plasmid pRT99gus containing genes for plant kanamycin resistance and for β-glucuronidase expression, and shoots were regenerated under kanamycin selection. PCR analysis of the regenerated transformed lines confirmed the presence of a 603 bp gus (uidA) gene fragment and a 1.5 kb fragment from the 35S promoter in three shoots from independent transformation events.
基金supported by Fudan University Recruitment Grant and the the Jane and Aatos Erkko Foundation.
文摘Despite tremendous progress made in human prostate biology over the past few decades,a full picture of prostate lineage hierarchy and its connection to cancer initiation remain to be delineated.Two recent studies published in Nat Genet.[1]and in Science[2]have profiled subpopulations of prostate cells at the single-cell level.Complementary analyses of data from the studies demonstrate self-renewal and differentiation capacities of different luminal epithelial cells,which can serve as cells of origin for prostate cancer.The system of lineage hierarchy controls cell differentiation and tissue formation from stem and progenitor cells,which may initiate cancer development if the process goes awry[3].Therefore,it is of great interest to identify cells with stemness or progenitor properties and delineate their lineage hierarchy in order to pinpoint the cells of origin for cancer when cellular genetics are altered[4].
文摘Astrocytes are implicated in the neuropathology of Alzheimer’s disease (AD) by clustering with other activated inflammatory cells at the sites of amyloid beta (Aβ) deposits formed in the cortex and hippocampus. Astrocytes are known to contribute to the clearance of Aβ in the AD brain. Also, adult but not neonatal mouse astrocytes are able to clear Aβ deposits from the tissue sections of transgenic AD mice and human brain ex vivo. Because these findings suggest that cultured neonatal astrocytes may not represent a relevant cell for modeling the function of astrocytes in neurodegenerative diseases, we studied whether neonatal and adult astrocytes show different responses in gene expression when exposed to brain sections burdened by deposits of human Aβ. Whole genome microbarrays demonstrated greater alteration of gene expression in adult astrocytes than in neonatal astrocytes. When exposed to Aβ burdened brain sections adult but not neonatal astrocytes up-regulated genes related to peptidase (such as MMP13, MMP12, Phex, Htra1), scavenger receptor (Scara5, Enpp2) and glutathioine transferase (Gsta1, Gsta2, Gclm) activity, suggesting increased ability to degrade and endocytose Aβ peptides and protect against oxidative bursts. Quantitative RT-PCR analysis confirmed the significant alteration in gene expression of key peptidases, scavenger receptors and cholesterol synthesis. Our data suggest that adult astrocytes in culture are more sensitive to disease-relevant stress showing more extensive genetic response compared to neonatal astrocytes. In addition, the identified peptidases and scavenger receptors which increase expression selectively in adult astrocytes suggest their major role in astrocyte-mediated clearance of Aβ deposits in AD.
