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1.
The β3-adrenergic receptor (β3AR) is expressed in visceral fat and is a regulator of resting metabolic rate, thermogenesis, and lipolysis. We genotyped 61 unrelated Mexican Americans for a variant in the β3AR gene (codon 64 TGGTrp→CGGArg; TRP64ARG). The allele frequency was 0.13. The TRP64ARG variant was significantly associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (41.3 ± 4.6 years vs 55.6 ± 2.6 years; P < 0.02) and in non-diabetics, with elevated 2-h insulin levels during an oral glucose tolerance test (810 ± 120 pmol/l vs 384 ± 6 pmol/l; P < 0.005). Non-diabetic subjects with the variant allele tended to have higher body mass indices (BMI), waist-to-hip ratios, and diastolic blood pressures. The study group was expanded to include 421 related subjects from 31 families in the San Antonio Family Diabetes Study. Using a measured genotype analysis approach to estimate genotype-specific means for each trait, those who were homozygous for the TRP64ARG variant had significantly higher 2-h insulin levels (P = 0.036) and trends towards higher BMI compared to the other two genotypes. We detected no associations of these traits in the TRP64ARG heterozygotes in the larger group. We conclude that the TRP64ARG β3AR variant is a susceptibility gene for several features of the insulin resistance syndrome in Mexican Americans. Since its effects are modest, study design (e.g., subject selection, genetic background, and statistical analyses) may influence which traits are associated with this variant and whether or not the effect is detectable in heterozygotes. Received: 7 April 1997 / Accepted: 22 July 1997  相似文献   

2.

Background

Prostate cancer (PCa) is the most frequently diagnosed cancer in North American men. Androgen-deprivation therapy (ADT) accentuates the infiltration of immune cells within the prostate. However, the immunosuppressive pathways regulated by androgens in PCa are not well characterized. Arginase 2 (ARG2) expression by PCa cells leads to a reduced activation of tumor-specific T cells. Our hypothesis was that androgens could regulate the expression of ARG2 by PCa cells.

Methodology/Principal Findings

In this report, we demonstrate that both ARG1 and ARG2 are expressed by hormone-sensitive (HS) and hormone-refractory (HR) PCa cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 was more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 were overexpressed. The regulation of arginase expression following androgen stimulation was dependent on the androgen receptor (AR), as a siRNA treatment targeting the AR inhibited both ARG1 and ARG2 overexpression. This observation was correlated in vivo in patients by immunohistochemistry. Patients treated by ADT prior to surgery had lower ARG2 expression in both non-malignant and malignant tissues. Furthermore, ARG1 and ARG2 were enzymatically active and their decreased expression by siRNA resulted in reduced overall arginase activity and l-arginine metabolism. The decreased ARG1 and ARG2 expression also translated with diminished LNCaP cells cell growth and increased PBMC activation following exposure to LNCaP cells conditioned media. Finally, we found that interleukin-8 (IL-8) was also upregulated following androgen stimulation and that it directly increased the expression of ARG1 and ARG2 in the absence of androgens.

Conclusion/Significance

Our data provides the first detailed in vitro and in vivo account of an androgen-regulated immunosuppressive pathway in human PCa through the expression of ARG1, ARG2 and IL-8.  相似文献   

3.
Contaminants such as heavy metals may contribute to the dissemination of antimicrobial resistance (AMR) by enriching resistance gene determinants via co-selection mechanisms. In the present study, a survey was performed on soils collected from four areas at the Savannah River Site (SRS), South Carolina, USA, with varying contaminant profiles: relatively pristine (Upper Three Runs), heavy metals (Ash Basins), radionuclides (Pond B) and heavy metal and radionuclides (Tim’s Branch). Using 16S rRNA gene amplicon sequencing, we explored the structure and diversity of soil bacterial communities. Sites with legacies of metal and/or radionuclide contamination displayed significantly lower bacterial diversity compared to the reference site. Metagenomic analysis indicated that multidrug and vancomycin antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) including those associated with copper, arsenic, iron, nickel and zinc were prominent in all soils including the reference site. However, significant differences were found in the relative abundance and diversity of certain ARGs and MRGs in soils with metal/radionuclide contaminated soils compared to the reference site. Co-occurrence patterns revealed significant ARG/MRG subtypes in predominant soil taxa including Acidobacteriaceae, Bradyrhizobium, Mycobacterium, Streptomyces, Verrumicrobium, Actinomadura and Solirubacterales. Overall, the study emphasizes the potential risk of human activities on the dissemination of AMR in the environment.  相似文献   

4.
Terrestrial life in Antarctica has been described as some of the simplest on the planet, and mainly confined to soil microfaunal communities. Studies have suggested that the lack of diversity is due to extreme environmental conditions and thought to be driven by abiotic factors. In this study we investigated soil microfauna composition, abundance, and distribution in East Antarctica, and assessed correlations with soil geochemistry and environmental variables. We examined 109 soil samples from a wide range of ice-free habitats, spanning 2000 km from Framnes Mountains to Bailey Peninsula. Microfauna across all samples were patchily distributed, from complete absence of invertebrates to over 1600 specimens/gram of dry weight of soil (gdw), with highest microfauna abundance observed in samples with visible vegetation. Bdelloid rotifers were on average the most widespread found in 87% of sampled sites and the most abundant (44 specimens/gdw). Tardigrades occurred in 57% of the sampled sites with an abundance of 12 specimens/gdw. Nematodes occurred in 71% of samples with a total abundance of 3 specimens/gdw. Ciliates and mites were rarely found in soil samples, with an average abundance of 1.3 and 0.04 specimens/gdw, respectively. We found that microfaunal composition and abundance were mostly correlated with the soil geochemical parameters; phosphorus, NO3 and salinity, and likely to be the result of soil properties and historic landscape formation and alteration, rather than the geographic region they were sampled from. Studies focusing on Antarctic biodiversity must take into account soil geochemical and environmental factors that influence population and species heterogeneity.  相似文献   

5.
Summary. Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r2 = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r2 = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.  相似文献   

6.
Microbial adaptation to environmental conditions is a complex process, including acquisition of positive traits through horizontal gene transfer or the modification of existing genes through duplication and/or mutation. In this study, we examined the adaptation of a Pseudomonas fluorescens isolate (R124) from the nutrient-limited mineral environment of a silica cave in comparison with P. fluorescens isolates from surface soil and the rhizosphere. Examination of metal homeostasis gene pathways demonstrated a high degree of conservation, suggesting that such systems remain functionally similar across chemical environments. The examination of genomic islands unique to our strain revealed the presence of genes involved in carbohydrate metabolism, aromatic carbon metabolism, and carbon turnover, confirmed through phenotypic assays, suggesting the acquisition of potentially novel mechanisms for energy metabolism in this strain. We also identified a twitching motility phenotype active at low-nutrient concentrations that may allow alternative exploratory mechanisms for this organism in a geochemical environment. Two sets of candidate twitching motility genes are present within the genome, one on the chromosome and one on a plasmid; however, a plasmid knockout identified the functional gene as being present on the chromosome. This work highlights the plasticity of the Pseudomonas genome, allowing the acquisition of novel nutrient-scavenging pathways across diverse geochemical environments while maintaining a core of functional stress response genes.  相似文献   

7.
Abstract

Krishna Godavari (KG) basin, located in the eastern continental margin of India, is a geological region well known for the abundance of economically important minerals. However, less is known about the microbial ecology of its subsurface sediments. The present study is the first report on the comprehensive culture-independent census of bacterial communities of deep subsurface of KG basin and their relationship with the geochemical environment. Elemental and mineralogical characterization of the sediments highlighted the presence of carbon and nitrogen deprived conditions along with the abundance of metalliferous minerals, especially rich in valuable elements like zirconium, vanadium, cesium, and rare earth elements. Diversity analysis based on Illumina MiSeq high-throughput sequencing platform revealed the predominance of Firmicutes (44.24%), Proteobacteria (34.17%), Bacteroidetes (15.18%), and Actinobacteria (3.81%) in the deep subsurface of this basin. ‘Abundant’ and ‘rare’ sub-communities analysis indicated that a large number of phyla like Acidobacteria, Armatimonadetes, Chloroflexi, and Deinococcus-Thermus were exclusively present as a rare community. Statistical analyses demonstrated that geochemical parameters, especially depth, pH, and metal content, showed significant influence on the microbial community structure. The present study should help future investigations for microbial mediated sustainable utilization of mineral-rich sediments of the region.  相似文献   

8.
侯磊  薛会英 《生态学报》2021,41(9):3564-3571
为了解重金属对青藏高原高寒草甸土壤线虫群落的影响,在邦杰塘草原利用公路源重金属含量差异,采用高通量测序技术,分析重金属对高寒草甸土壤线虫群落多样性及群落组成的影响。结果表明:在重金属含量较低样本中,土壤线虫群落Shannon指数、Ace指数、Chao指数比重金属含量较高样本均要小,且整体上Shannon指数、Ace指数、Chao指数与重金属含量较高样本差异显著(P<0.05)。重金属含量升高改变了高寒草甸土壤线虫纲水平和目水平的群落结构,使近自然状况下的色矛纲(Chromadorea)、小杆目(Rhabdtida)优势土壤线虫群落转变为一类未分类线虫纲(unclassified_p_Nematoda)、一类未分类线虫目(unclassified_p_Nematoda)的优势土壤线虫群落。重金属Cu、Pb、Zn、Cd与线虫门(Nematoda)和刺嘴纲(Enoplea)正相关,但与色矛纲(Chromadorea)负相关,且对土壤线虫Chao指数的变异解释比例依次减小。研究表明土壤重金属含量对青藏高原高寒草甸土壤线虫群落多样性及组成产生很大影响,但仍需对高寒草甸区域进行系统的土壤线虫调查,并丰富土壤线虫生物信息数据库。  相似文献   

9.
10.
Seed banks represent a reservoir of propagules important for understanding plant population dynamics. Seed viability in soil depends on soil abiotic conditions, seed species, and soil biota. Compared to the vast amount of data on plant growth effects, next to nothing is known about how arbuscular mycorrhizal fungi (AMF) could influence viability of seeds in the soil seed bank. To test whether AMF could influence seed bank viability, we conducted three two‐factorial experiments using seeds of three herbaceous plant species (Taraxacum officinale, Dactylis glomerata, and Centaurea nigra) under mesocosm (experiments 1 and 2) and field conditions (experiment 3) and modifying the factor AMF presence (yes and no). To allow only hyphae to grow in and to prevent root penetration, paired root exclusion compartments (RECs) were used in experiments 2 and 3, which were either rotated (interrupted mycelium connection) or kept static (allows mycorrhizal connection). After harvesting, seed viability, soil water content, soil phosphorus availability, soil pH, and hyphal length in RECs were measured. In experiment 1, we used inoculation or not with the AMF Rhizophagus irregularis to establish the mycorrhizal treatment levels. A significant negative effect of mycorrhizal hyphae on viability of seeds was observed in experiments 1 and 3, and a similar trend in experiment 2. All three experiments showed that water content, soil pH, and AMF extraradical hyphal lengths were increased in the presence of AMF, but available P was decreased significantly. Viability of seeds in the soil seed bank correlated negatively with water content, soil pH, and AMF extraradical hyphal lengths and positively with soil P availability. Our results suggest that AMF can have a negative impact on soil seed viability, which is in contrast to the often‐documented positive effects on plant growth. Such effects must now be included in our conceptual models of the AM symbiosis.  相似文献   

11.
12.
We examined the effects of forest stand age on soil respiration (SR) including the heterotrophic respiration (HR) and autotrophic respiration (AR) of two forest types. We measured soil respiration and partitioned the HR and AR components across three age classes ∼15, ∼25, and ∼35-year-old Pinus sylvestris var. mongolica (Mongolia pine) and Larix principis-rupprechtii (larch) in a forest-steppe ecotone, northern China (June 2006 to October 2009). We analyzed the relationship between seasonal dynamics of SR, HR, AR and soil temperature (ST), soil water content (SWC) and normalized difference vegetation index (NDVI, a plant greenness and net primary productivity indicator). Our results showed that ST and SWC were driving factors for the seasonal dynamics of SR rather than plant greenness, irrespective of stand age and forest type. For ∼15-year-old stands, the seasonal dynamics of both AR and HR were dependent on ST. Higher Q10 of HR compared with AR occurred in larch. However, in Mongolia pine a similar Q10 occurred between HR and AR. With stand age, Q10 of both HR and AR increased in larch. For Mongolia pine, Q10 of HR increased with stand age, but AR showed no significant relationship with ST. As stand age increased, HR was correlated with SWC in Mongolia pine, but for larch AR correlated with SWC. The dependence of AR on NDVI occurred in ∼35-year-old Mongolia pine. Our study demonstrated the importance of separating autotrophic and heterotrophic respiration components of SR when stimulating the response of soil carbon efflux to environmental changes. When estimating the response of autotrophic and heterotrophic respiration to environmental changes, the effect of forest type on age-related trends is required.  相似文献   

13.
14.
植物回收衰老叶片的氮是植物重要的养分保持和环境适应机制,在寒旱贫瘠的生境更是如此。为了理解降水梯度上植物对高寒贫瘠环境的养分适应特征,研究了羌塘高寒草原优势物种紫花针茅叶片氮回收策略及其与环境因子的关系。结果表明,降水梯度带上紫花针茅叶片具有较高的叶氮水平和氮回收能力。生长季盛期紫花针茅绿叶平均氮含量为(23.87±3.92)g/kg,高于中国草地平均水平(20.9 g/kg)及全球平均值(20.1 g/kg);绿叶氮含量与年降水量(MAP)呈显著负相关,干旱端(西部)绿叶中氮含量明显高于湿润端(东部)。枯叶养分回收后的氮水平(NRP)很低,平均为(6.76±1.42)g/kg,叶片平均氮回收效率(NRE)为(71.25±6.46)%,明显高于中国温带草原和全球的平均水平(46.9%—58.5%)。枯叶中氮回收水平对叶片氮回收效率起决定作用,是维持高养分回收效率的物质基础。NRE与MAP、土壤全氮(TN)和土壤无机氮呈显著负相关;NRP与TN相关性不显著,但与土壤无机氮显著负相关。尽管NRE与NRP呈显著负相关,但二者与绿叶氮含量均没有显著相关性。年均气温、海拔对NRE和NRP影响均不显著。因此,紫花针茅叶片极高的NRE和低NRP反映了它对极端干旱贫瘠环境的养分保持能力,通过内部氮循环来降低养分流失。土壤氮的有效性是影响紫花针茅叶片氮回收能力的关键因子,降水通过影响土壤氮的有效性以及绿叶中氮含量间接影响紫花针茅叶片氮回收效率。  相似文献   

15.
Sediment cores taken from Great Slave Lake, Canada, were analysed to investigate their metabolically active microbial populations and geochemistry. The amplification of cDNA detected metabolically active bacterial (50 separate bands) and archaeal (49 separate band) communities. The bacterial communities were further resolved indicating active actinobacterial and γ-proteobacterial communities (36 and 43 individual bands respectively). Redundancy discriminate analysis and Monte Carlo permutation testing demonstrated the significant impact of geochemical parameters on microbial community structures. Geochemical analyses suggest that the upper 0.4 m represents soil weathering and erosion in the lake catchment. An increase in organic carbon in the lower core suggests either more primary productivity, indicating warmer climate conditions, associated with Holocene Climatic Optimum conditions pre 5,000 years BP or change from a reducing environment in the lower core to an oxidizing environment during more recent deposition. Drivers for bacterial, archaeal and actinobacterial community structures were sediment particle size, and its mineral composition. Depth also significantly affected γ- proteobacterial community structure. In contrast the organic carbon content did not significantly shape the microbial community structures within the sediment. This study indicates that geochemical parameters significantly contribute to microbial community structure in these sediments.  相似文献   

16.
A metagenomic approach and network analysis was used to investigate the wide-spectrum profiles of antibiotic resistance genes (ARGs) and their co-occurrence patterns in 50 samples from 10 typical environments. In total, 260 ARG subtypes belonging to 18 ARG types were detected with an abundance range of 5.4 × 10−6–2.2 × 10−1 copy of ARG per copy of 16S-rRNA gene. The trend of the total ARG abundances in environments matched well with the levels of anthropogenic impacts on these environments. From the less impacted environments to the seriously impacted environments, the total ARG abundances increased up to three orders of magnitude, that is, from 3.2 × 10−3 to 3.1 × 100 copy of ARG per copy of 16S-rRNA gene. The abundant ARGs were associated with aminoglycoside, bacitracin, β-lactam, chloramphenicol, macrolide-lincosamide-streptogramin, quinolone, sulphonamide and tetracycline, in agreement with the antibiotics extensively used in human medicine or veterinary medicine/promoters. The widespread occurrences and abundance variation trend of vancomycin resistance genes in different environments might imply the spread of vancomycin resistance genes because of the selective pressure resulting from vancomycin use. The simultaneous enrichment of 12 ARG types in adult chicken faeces suggests the coselection of multiple ARGs in this production system. Non-metric multidimensional scaling analysis revealed that samples belonging to the same environment generally possessed similar ARG compositions. Based on the co-occurrence pattern revealed by network analysis, tetM and aminoglycoside resistance protein, the hubs of the ARG network, are proposed to be indicators to quantitatively estimate the abundance of 23 other co-occurring ARG subtypes by power functions.  相似文献   

17.
Lead transformation to pyromorphite by fungi   总被引:1,自引:0,他引:1  
Lead (Pb) is a serious environmental pollutant in all its chemical forms [1]. Attempts have been made to immobilize lead in soil as the mineral pyromorphite using phosphate amendments (e.g., rock phosphate, phosphoric acid, and apatite [2-5]), although our work has demonstrated that soil fungi are able to transform pyromorphite into lead oxalate [6, 7]. Lead metal, an important structural and industrial material, is subject to weathering, and soil contamination also occurs through hunting and shooting [8, 9]. Although fungi are increasingly appreciated as geologic agents [10-12], there is a distinct lack of knowledge about their involvement in lead geochemistry. We examined the influence of fungal activity on lead metal and discovered that metallic lead can be transformed into chloropyromorphite, the most stable lead mineral that exists. This is of geochemical significance, not only regarding lead fate and cycling in the environment but also in relation to the phosphate cycle and linked with microbial transformations of inorganic and organic phosphorus. This paper provides the first report of mycogenic chloropyromorphite formation from metallic lead and highlights the significance of this phenomenon as a biotic component of lead biogeochemistry, with additional consequences for microbial survival in lead-contaminated environments and bioremedial treatments for Pb-contaminated land.  相似文献   

18.
Tran TM  Jorgensen R  Clark RB 《Biochemistry》2007,46(50):14438-14449
Characterization of the GRKs participating in the phosphorylation of the beta2-adrenergic receptor (beta2AR) have in part been limited by the lack of a simple cell-free assay with membrane-bound beta2AR and GRKs. We describe here a cell-free assay for GRK phosphorylation of the beta2AR in a postnuclear 600g fraction and washed membranes by intrinsic GRK activity using the GRK phosphosite-specific antibody that recognizes pS(355,356). Treatment of these cell-free preparations with 1.0 microM isoproterenol (ISO) caused a rapid maximal 10-15-fold increase in GRK site phosphorylation of the beta2AR (t1/2 = 1 min) with an EC50 for ISO stimulation of approximately 80 nM. Extensively washed plasma membrane fractions retained the 10-15-fold ISO stimulation of GRK site phosphorylation and GRK5 levels while being depleted of GRK2 and GRK6. Stimulation of GRK site phosphorylation by a range of partial agonists correlated well with their intrinsic efficacy for stimulation of adenylyl cyclase. GRK phosphorylation of the beta2AR in the washed membrane fraction caused minimal desensitization of ISO stimulation of adenylyl cyclase activity. Association of GRK5 with the beta2AR in intact cells was demonstrated by a high level of basal BRET2 using beta2AR-Rluc and GRK5-GFP2 that was not diminished by agonist stimulation. BRET2 between the beta2AR-Rluc and GFP2-betaarrestin 2 was increased by agonist, whereas BRET2 between the beta2AR and GRK2-GFP2 was not significant. On the basis of the level of GRK5-mediated phosphorylation we observe in isolated membrane fractions and co-localization of the beta2AR and GRK5, we conclude that GRK5 plays a distinctive role in the phosphorylation of the beta2AR.  相似文献   

19.
目的:探讨变应性鼻炎(AR)患者血清25-羟维生素D[25(OH)D]水平与总免疫球蛋白E(TIgE)及白细胞介素-13(IL-13)的相关性.方法:收集2016年7月至2018年12月期间本院收治的AR患者93例为AR组,根据病情严重程度分为轻度组23例,中度组39例,重度组31例,同期在我院体检的健康体检者93例为...  相似文献   

20.
徐岩  李静  方文 《生态学报》2022,42(4):1512-1526
2017年起,农业部连续多年出台化肥减量增效行动工作方案,要求适当增加有机肥投入,发展循环农业。但连续施用的有机肥进入土壤后,会对土壤pH、有机质和重金属含量等产生影响,改变土壤重金属行为。科学评估有机肥料施用的影响至关重要。仅通过总含量评估重金属污染风险被认为是片面的,不同化学提取剂提取的重金属含量不能完全代表实际污染状况。地球化学模型具有良好的适用性,比传统的提取方法能够更全面地解释重金属的行为。在集约化农业种植区黄淮海平原,多次施用不同比例的粪源有机肥于旱地菜田,并引入地球化学模型,结合pH依赖性浸出试验,明确连续施肥对菜田土壤重金属行为的主要影响机制。研究发现,有机肥中的铜锌含量远高于土壤中的含量,施用后,它们在土壤中的淋溶浓度随着施用比例增加而显著增加,最多可超过十倍以上,并且活性大大增加,与施肥后溶解性有机物含量的升高呈正相关。不同处理条件下的土壤重金属浸出趋势相似:在中性pH下浸出浓度最低,然后逐渐向强酸和强碱增加,呈现出V型变化。地球化学模型LeachXS展示出较好的模拟结果,其模拟值与实测浓度具有良好的相关性(71.02%)。模拟结果显示,有机肥的施用不会明显改变重金...  相似文献   

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