共查询到20条相似文献,搜索用时 0 毫秒
1.
How to be early flowering: an evolutionary perspective 总被引:3,自引:0,他引:3
In wild and cultivated annual plant species, flowering time is an important life-history trait that coordinates the life cycle with local environmental conditions. Extensive studies on the genetic basis of flowering time in the model species Arabidopsis thaliana have revealed a complex genetic network that can detect environmental and internal signals. Based on this knowledge and on known pleiotropic effects associated with flowering time genes, we suggest that a natural shift towards an early-flowering life cycle might involve only particular functional regions in a limited number of genes. Our predictions are supported by genetic theories of adaptation and by recent data about genes associated with natural variation. We analyse the extent to which these predictions can also apply to crop species. 相似文献
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Savidge TC 《Neuron glia biology》2007,3(3):191-197
The blood-brain barrier (BBB) is a specialized tissue interface that provides an important homeostatic and immunosurveillance role in the CNS. Unlike most microvascular tissues, which readily promote paracellular passage of solutes and macromolecules, the BBB is more analogous to polarized mucosal epithelia that restrict such permeability in order to prevent disease onset. Recent transgenic ablation studies have demonstrated that the BBB and mucosal tissues also share a requirement for astroglial-regulated barrier integrity. This review highlights the emerging concept that astroglia regulate barrier function at markedly different tissue interfaces. It also explores possible lessons that might be learnt by adopting epithelial model paradigms of the BBB. For example, novel glial-derived S-nitrosylation signals that regulate intestinal permeability in the digestive tract might provide new mechanistic insights into the function of the BBB. A better understanding of such universal mechanisms for barrier regulation will facilitate novel therapeutic strategies that target permeability disorders at CNS and mucosal tissue interfaces. 相似文献
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PURPOSE OF REVIEW: Vascular calcification is frequently found in patients with osteoporosis, atherosclerosis and chronic kidney disease, leading to high morbidity and mortality rates. The effects of vitamin D excess and deficiency on vascular calcification are reviewed in this article. RECENT FINDINGS: There is evidence from experimental studies that mediacalcinosis induced by vitamin D excess is an active and reversible process. Vitamin D excess, however, is rarely seen in the general human population. Experimental data also demonstrate that physiologic vitamin D actions include the inhibition of processes that are important for intimal and medial artery calcification such as pro-inflammatory cytokine release, adhesion molecule release, and proliferation and migration of vascular smooth muscle cells. In uremic rats, low levels of the vitamin D hormone calcitriol are associated with massive vascular and soft tissue calcifications. Whereas retrospective studies already indicate a beneficial effect of active vitamin D on mortality rates in chronic kidney disease, little is yet known about the effect of vitamin D deficiency on cardiovascular morbidity and mortality in the general population. SUMMARY: Available data indicate that vitamin D exerts a biphasic 'dose response' curve on vascular calcification with deleterious consequences not only of vitamin D excess but also of vitamin D deficiency. 相似文献
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Jeffrey J. Hsu Michael S. Huang Andrew P. Sage Peter Tontonoz Linda L. Demer Yin Tintut 《FEBS letters》2009,583(8):1344-33706
We examined the effect of liver X receptor (LXR) agonists on vascular calcification, prevalent in atherosclerotic lesions. T0901317, an LXR agonist, augmented protein kinase A (PKA)-induced mineralization and alkaline phosphatase (ALP) activity in aortic smooth muscle cells isolated from wild-type, but not from Lxrβ−/−mice. A six-hour T0901317 treatment augmented the PKA-induced expression of the phosphate transporter Pit-1, a positive regulator of mineralization, suggesting a direct role. A ten-day T0901317 treatment attenuated PKA-induced expression of mineralization inhibitors, osteopontin and ectonucleotide pyrophosphatase/phosphodiesterase-1, suggesting an indirect role. The effects of T0901317 were attenuated by inhibition of ALP, Pit-1 and Rho-associated kinase, but not by inhibition of PKA. These results suggest that T0901317-augmented mineralization occurs downstream of PKA, involving both direct and indirect LXR-mediated pathways. 相似文献
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Yue Liu Ye Bo Zhou Gai Gai Zhang Yan Cai Xiao Hui Duan Xu Teng Jun Qiu Song Yi Shi Chao Shu Tang Xin Hua Yin Yong Fen Qi 《Regulatory peptides》2010,159(1-3):35-43
Cortistatin (CST) is a newly discovered polypeptide with multiple biological activities that plays a regulatory role in the nervous, endocrine and immune systems. However, the role of CST in the pathogenesis of cardiovascular diseases remains unclear. In this study, we investigated in rats whether CST inhibits vascular calcification induced by vitamin D3 and nicotine treatment in vivo and calcification of cultured rat vascular smooth muscular cells (VSMCs) induced by beta-glycerophosphate in vitro and the underlying mechanism. We measured rat hemodynamic variables, alkaline phosphatase (ALP) activity, calcium deposition and pathological changes in aortic tissues and cultured VSMCs. CST treatment significantly improved hemodynamic values and arterial compliance in rats with vascular calcification, by decreasing systolic blood pressure, pulse pressure, left ventricular end-systolic pressure and left ventricular end-diastolic pressure. CST also significantly decreased ALP activity and calcium deposition, alleviated pathological injury and down-regulated the mRNA expression of type III sodium-dependent phosphate co-transporter-1 (Pit-1) in aortic tissues. It dose-independently inhibited the calcification of VSMCs by decreasing ALP activity and calcium deposition, alleviating pathologic injury and down-regulating Pit-1 mRNA expression. As with CST treatment, ALP activation and calcium deposition were decreased significantly on treatment with ghrelin, the endogenous agonist of growth hormone secretagogue receptor 1a (GHSR1a), but not significantly with somatostatin-14 or proadrenomedullin N-terminal 20 peptide in VSMCs. Further, growth hormone-releasing peptide-6[D-lys], the endogenous antagonist of GHSR1a, markedly reversed the increased ALP activity and calcium deposition in VSMCs. CST could be a new target molecule for the prevention and therapy of vascular calcification, whose effects are mediated by GHSR1a rather than SSTRs or Mrg X2. 相似文献
7.
Mental health crucially depends upon affective states such as emotions, stress responses, impulses and moods. These states shape how we think, feel and behave. Often, they support adaptive functioning. At other times, however, they can become detrimental to mental health via maladaptive affect generation processes and/or maladaptive affect regulation processes. Here, we present an integrative framework for considering the role of affect generation and regulation in mental illness and well‐being. Our model views affect generation as an iterative cycle of attending to, appraising and responding to situations. It views affect regulation as an iterative series of decisions aimed at altering affect generation. Affect regulation decisions include identifying what, if anything, should be changed about affect, selecting where to intervene in the affect generation cycle, choosing how to implement this intervention, and monitoring the regulation attempt to decide whether to maintain, switch or stop it. Difficulties with these decisions, often arising from biased inputs to them, can contribute to manifestations of mental illness such as clinical symptoms, syndromes and disorders. The model has a number of implications for clinical assessment and treatment. Specifically, it offers a common set of concepts for characterizing different affective states; it highlights interactions between affect generation and affect regulation; it identifies assessment and treatment targets among the component processes of affect regulation; and it is applicable to prevention and treatment of mental illness as well as to promotion and restoration of psychological well‐being. 相似文献
8.
Adair TH 《American journal of physiology. Regulatory, integrative and comparative physiology》2005,289(2):R283-R296
The importance of metabolic factors in the regulation of angiogenesis is well understood. An increase in metabolic activity leads to a decrease in tissue oxygenation causing tissues to become hypoxic. The hypoxia initiates a variety of signals that stimulate angiogenesis, and the increase in vascularity that follows promotes oxygen delivery to the tissues. When the tissues receive adequate amounts of oxygen, the intermediate effectors return to normal levels, and angiogenesis ceases. An emerging concept is that adenosine released from hypoxic tissues has an important role in driving the angiogenesis. The following feedback control hypothesis is proposed: AMP is dephosphorylated by ecto-5'-nucleotidase, producing adenosine under hypoxic conditions in the extracellular space adjacent to a parenchymal cell (e.g., cardiomyocyte, skeletal muscle fiber, hepatocyte, etc.). Extracellular adenosine activates A(2) receptors, which stimulates the release of vascular endothelial growth factor (VEGF) from the parenchymal cell. VEGF binds to its receptor (VEGF receptor 2) on endothelial cells, stimulating their proliferation and migration. Adenosine can also stimulate endothelial cell proliferation independently of VEGF, which probably involves modulation of other proangiogenic and antiangiogenic growth factors and perhaps an intracellular mechanism. In addition, hemodynamic factors associated with adenosine-induced vasodilation may have a role in the development and remodeling of the vasculature. Once a new capillary network has been established, and the diffusion/perfusion capabilities of the vasculature are sufficient to supply the parenchymal cells with adequate amounts of oxygen, adenosine and VEGF as well as other proangiogenic and antiangiogenic growth factors return to near-normal levels, thus closing the negative feedback loop. The available data indicate that adenosine might be an essential mediator for up to 50-70% of the hypoxia-induced angiogenesis in some situations; however, additional studies in intact animals will be required to fully understand the quantitative importance of adenosine. 相似文献
9.
Fine structure of early cartilage calcification 总被引:21,自引:0,他引:21
E Bonucci 《Journal of ultrastructure research》1967,20(1):33-50
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Jan-Hendrik S. Hofmeyr 《Journal of bioenergetics and biomembranes》1995,27(5):479-490
A possible basis for a quantitative theory of metabolic regulation is outlined. Regulation is defined here as the alteration of reaction properties to augment or counteract the mass-action trend in a network reactions. In living systems the enzymes that catalyze these reactions are the handles through which such alteration is effected. It is shown how the elasticity coefficients of an enzyme-catalyzed reaction with respect to substrates and products are the sum of a massaction term and a regulatory kinetic term; these coefficients therefore distinguish between massaction effects and regulatory effects and are recognized as the key to quantifying regulation. As elasticity coefficients are also basic ingredients of metabolic control analysis, it is possible to relate regulation to such concepts as control, signalling, stability, and homeostasis. The need for care in the choice of relative or absolute changes when considering questions of metabolic regulation is stressed. Although the concepts are illustrated in terms of a simple coupled reaction system, they apply equally to more complex systems. When such systems are divided into reaction blocks, co-response coefficients can be used to measure the elasticities of these blocks.I dedicate this paper to Henrik Kacser, co-founder of and guiding light in the field of metabolic control analysis. His recent death leaves us bereft of a fount of wisdom and kindness, but his work remains as a monument along the path of our search for an understanding of metabolic behavior. 相似文献
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Ting TC Miyazaki-Anzai S Masuda M Levi M Demer LL Tintut Y Miyazaki M 《The Journal of biological chemistry》2011,286(27):23938-23949
Vascular calcification is recognized as an independent predictor of cardiovascular mortality, particularly in subjects with chronic kidney disease. However, the pathways by which dysregulation of lipid and mineral metabolism simultaneously occur in this particular population remain unclear. We have shown that activation of the farnesoid X receptor (FXR) blocks mineralization of bovine calcifying vascular cells (CVCs) and in ApoE knock-out mice with 5/6 nephrectomy. In contrast to FXR, this study showed that liver X receptor (LXR) activation by LXR agonists and adenovirus-mediated LXR overexpression by VP16-LXRα and VP16-LXRβ accelerated mineralization of CVCs. Conversely, LXR inhibition by dominant negative (DN) forms of LXRα and LXRβ reduced calcium content in CVCs. The regulation of mineralization by FXR and LXR agonists was highly correlated with changes in lipid accumulation, fatty acid synthesis, and the expression of sterol regulatory element binding protein-1 (SREBP-1). The rate of lipogenesis in CVCs through the SREBP-1c dependent pathway was reduced by FXR activation, but increased by LXR activation. SREBP-1c overexpression augmented mineralization in CVCs, whereas SREBP-1c DN inhibited alkaline phosphatase activity and mineralization induced by LXR agonists. LXR and SREBP-1c activations increased, whereas FXR activation decreased, saturated and monounsaturated fatty acids derived from lipogenesis. In addition, we found that stearate markedly promoted mineralization of CVCs as compared with other fatty acids. Furthermore, inhibition of either acetyl-CoA carboxylase or acyl-CoA synthetase reduced mineralization of CVCs, whereas inhibition of stearoyl-CoA desaturase induced mineralization. Therefore, a stearate metabolite derived from lipogenesis might be a risk factor for the development of vascular calcification. 相似文献
13.
Endothelin-1 is a potent regulator in vivo in vascular calcification and in vitro in calcification of vascular smooth muscle cells 总被引:13,自引:0,他引:13
We observed changes of endothelin content and endothelin mRNA in vivo in vascular calcification and in vitro in calcification of vascular smooth muscle cells to explore the role of endothelin in vascular calcification. Calcification model in vivo was induced by administration of Vitamin D(3) plus nicotine. Calcification of vascular smooth muscle cells (VSMCs) was induced by beta-glycerophosphate. Endothelin content was measured by using radioimmunoassay. Endothelin mRNA amount was determined by using competitive quantitative RT-PCR. The results showed that calcium content, 45Ca(2+) uptake and alkaline phosphatase (ALP) activity were increased in calcified VSMCs, compared with controls, but were decreased, compared with calcified VSMCs plus BQ123 group. The endothelin content in the medium and endothelin mRNA in VSMCs were elevated by 35 and 120% (P<0.05), respectively, compared with those normal VSMCs. Calcium content, 45Ca(2+) accumulation and ALP activity in calcified arteries increased by 5.0-, 1.4-, and 1.4-fold. The endothelin levels in plasma and aorta as well as the amount of endothelin mRNA in calcified aorta were increased by 102, 103, and 22%, respectively, compared with control group. However, calcium content, 45Ca(2+) uptake and ALP activity in VDN plus bosentan group was 33, 36.7, and 40.4% lower than those in VDN group. These results indicated an upregulated endothelin gene expression as well as an increased production of endothelin in calcified aorta and VSMCs with BQ123 and bosentan significantly reducing vascular calcification. This suggested that endothelin might be involved in pathogenesis of vascular calcification. 相似文献
14.
Huang MS Sage AP Lu J Demer LL Tintut Y 《Biochemical and biophysical research communications》2008,374(3):553-558
Vascular calcification is associated with increased cardiovascular risk and occurs by osteochondrogenic differentiation of vascular cells. Many of the same regulatory factors that control skeletal mineralization, including the complex metabolic pathway controlling levels of the activator, inorganic phosphate, and the potent inhibitor, pyrophosphate, also govern vascular calcification. We previously found that the cAMP/PKA signaling pathway mediates in vitro vascular cell calcification induced by inflammatory factors including tumor necrosis factor-alpha 1 and oxidized phospholipids. In this report, we tested whether this signaling pathway modulates phosphate and pyrophosphate metabolism. Treatment of primary murine aortic cells with the PKA activator, forskolin, significantly induced osteoblastic differentiation markers, including alkaline phosphatase (ALP), osteopontin, and osteocalcin as well as the pyrophosphate generator, ectonucleotide-pyrophosphatase/phosphodiesterase-1 (Enpp1) and the pyrophosphate transporter, ankylosis protein, but not the sodium/phosphate cotransporter, Pit-1. In the presence of a substrate for ALP, beta-glycerophosphate, which generates inorganic phosphate, forskolin also enhanced matrix mineralization. Inhibitors of ALP or Pit-1 abrogated forskolin-induced osteopontin expression and mineralization but not forskolin-induced osteocalcin or ALP. These results suggest that phosphate is necessary for PKA-induced calcification of vascular cells and that the extent of PKA-induced calcification is controlled by feedback induction of the inhibitor, pyrophosphate. 相似文献
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血管钙化常见于动脉粥样硬化、糖尿病、慢性肾功能衰竭及衰老的血管.近年来的研究证实血管钙化的发生是一种类似于生理性矿化的主动调节过程,而非单纯的钙磷的被动沉积.血管细胞外基质是血管的主要组成成分,对血管起支持、保护作用,且与血管壁细胞相互作用影响其粘附、增殖、迁移、分化等功能,同时又是各种生长因子和细胞因子的储存库.目前的研究显示,在血管钙化过程中细胞外基质的组成和表达可能发生了变化,并参与了对钙化进程的主动调节.基质水解酶可能通过基质降解依赖或非依赖的机制,在钙化的发生发展中起到重要作用.本文主要综述了在血管钙化过程中细胞外基质的变化及其对血管钙化的作用,以及基质水解酶对血管钙化过程可能的影响. 相似文献
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目的:在大鼠血管钙化模型上,探讨高同型半胱氨酸血症对血管钙化的影响及其作用机制.方法:用维生素D3加尼古丁诱导大鼠血管钙化模型,并给以高蛋氨酸饮食六周诱导大鼠高同型半胱氨酸血症,用高效液相色谱法检测血浆总同型半胱氨酸(Hcy)水平;采用血管组织vonKossa染色、钙含量测定、碱性磷酸酶(ALP)活性和骨钙素(OC)含量测定以判断血管钙化程度,同时测定血浆脂质共轭烯(Diene键)含量反映其脂质过氧化水平.结果:钙化组大鼠血管yon Kossa染色可见大量黑色颗粒沉积,其血管的钙含量,碱性磷酸酶活性及骨钙素含量分别较对照组增加8.09倍、45.57%和2.81倍(P<0.01).高蛋氨酸饮食的钙化组大鼠血管内钙含量较单纯钙化组增高了34.29%,而碱性磷酸酶活性及骨钙素含量则较单纯的钙化组降低29.13%和74.69%(P<0.01).钙化组大鼠血浆脂质共轭烯含量与对照组比较无显著性差异,单纯高蛋氨酸饮食和钙化加高蛋氨酸饮食大鼠血浆脂质共轭烯含量较对照组增加了1.93和2.89倍(P<0.01),而钙化加高蛋氨酸饮食大鼠血浆脂质共轭烯含量较单纯高蛋氨酸饮食大鼠又增加了32.90%(P<0.01).结论:高同型半胱氨酸血症可以促进血管的钙化,可能与其所致的脂质过氧化程度增强有关. 相似文献
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Schreiber AM 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2001,129(2-3):587-595
Flatfish (Pleuronectiformes) distribution in the environment is influenced by salinity, and varies among species and with developmental stage. Osmoregulatory ability likely plays an important role in defining species and developmental stage-specific distribution. Although the mechanisms of osmoregulation in adult and juvenile teleosts have been widely addressed, far less is known about their larval osmoregulatory physiology. Much of our current understanding of larval fish ion-regulation stems from studies using flatfishes, and this article reviews advances in this field, primarily from the point of view of the developing flatfishes. Addressed here are the ontogeny of salinity tolerance, the development of several important osmoregulatory tissues (the skin, gut, and gill), and the influence of the endocrine system on osmoregulation during early larval development and metamorphosis. 相似文献
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Geng Y Hsu JJ Lu J Ting TC Miyazaki M Demer LL Tintut Y 《The Journal of biological chemistry》2011,286(38):33701-33706
Vascular calcification impairs vessel compliance and increases the risk of cardiovascular events. We found previously that liver X receptor agonists, which regulate intracellular cholesterol homeostasis, augment PKA agonist- or high phosphate-induced osteogenic differentiation of vascular smooth muscle cells. Because cholesterol is an integral component of the matrix vesicles that nucleate calcium mineral, we examined the role of cellular cholesterol metabolism in vascular cell mineralization. The results showed that vascular smooth muscle cells isolated from LDL receptor null (Ldlr(-/-)) mice, which have impaired cholesterol uptake, had lower levels of intracellular cholesterol and less osteogenic differentiation, as indicated by alkaline phosphatase activity and matrix mineralization, compared with WT cells. PKA activation with forskolin acutely induced genes that promote cholesterol uptake (LDL receptor) and biosynthesis (HMG-CoA reductase). In WT cells, inhibition of cholesterol uptake by lipoprotein-deficient serum attenuated forskolin-induced matrix mineralization, which was partially reversed by the addition of cell-permeable cholesterol. Prolonged activation of both uptake and biosynthesis pathways by cotreatment with a liver X receptor agonist further augmented forskolin-induced matrix mineralization. Inhibition of either cholesterol uptake, using Ldlr(-/-) cells, or of cholesterol biosynthesis, using mevastatin-treated WT cells, failed to inhibit matrix mineralization due to up-regulation of the respective compensatory pathway. Inhibition of both pathways simultaneously using mevastatin-treated Ldlr(-/-) cells did inhibit forskolin-induced matrix mineralization. Altogether, the results suggest that up-regulation of cholesterol metabolism is essential for matrix mineralization by vascular cells. 相似文献
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Sutliff RL Walp ER El-Ali AM Elkhatib S Lomashvili KA O'Neill WC 《American journal of physiology. Renal physiology》2011,301(1):F78-F83
The contribution of medial calcification to vascular dysfunction in renal failure is unknown. Vascular function was measured ex vivo in control, noncalcified uremic, and calcified uremic aortas from rats with adenine-induced renal failure. Plasma urea was 16 ± 4, 93 ± 14, and 110 ± 25 mg/dl, and aortic calcium content was 27 ± 4, 29 ± 2, and 4,946 ± 1,616 nmol/mg dry wt, respectively, in the three groups. Maximal contraction by phenylephrine (PE) or KCl was reduced 53 and 63% in uremic aortas, and sensitivity to KCl but not PE was increased. Maximal relaxation to acetylcholine was impaired in uremic aortas (30 vs. 65%), and sensitivity to nitroprusside was also reduced, indicating some impairment of endothelium-independent relaxation as well. None of these parameters differed between calcified and noncalcified uremic aortas. However, aortic compliance was reduced in calcified aortas, ranging from 17 to 61% depending on the severity of calcification. We conclude that uremic vascular calcification, even when not severe, significantly reduces arterial compliance. Vascular smooth muscle and endothelial function are altered in renal failure but are not affected by medial calcification, even when severe. 相似文献