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1.
Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific intermediate in the cholesterol biosynthetic pathway. To test the feasibility of lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology. Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol biosynthesis in the liver slices was almost eliminated. Although the hepatic squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of cholesterol and its precursors distal to squalene were indistinguishable from those of control mice, indicating the presence of sufficient centripetal flow of cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice showed a transient liver dysfunction with moderate hepatomegaly presumably secondary to increased farnesol production. In a fed state, the plasma total cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic effect was lost. mRNA expression of liver X receptor α target genes was reduced, while that of sterol-regulatory element binding protein 2 target genes was increased. In conclusion, liver-specific ablation of SS inhibits hepatic cholesterol biosynthesis and induces hypolipidemia without increasing significant mortality.  相似文献   
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Coronary Artery Disease (CAD) is a major killer disease throughout the world. Dyslipidemia is a major contributor to the risk of CAD. Several dietary articles traditionally used in India and other South Asian countries reduced dyslipidemia. The present study was undertaken to evaluate the combined effect of Mung bean (Vigna radiata) and Elephant foot yam (Amorphophallus paeoniifolius) on serum lipids and atherogenic indices in albino rats and to compare it with a standard drug Cholestyramine. Thirty healthy albino rats of both sexes (150–200 g) were randomized to 5 groups of 6 animals each. The grouping were done based on the following criteria: Group I: Normal Control Group, Group II: (Standard Group): Cholestyramine resin 5 mg/kg bw, Group III: (Half Dose Group): Drug powder at 540 mg/kg bw, Group IV: (Effective Dose Group): Drug powder at 1080 mg/kg bw, and Group V: (Double Dose Group): Drug powder at 2160 mg/kg bw. Lipid profile was estimated at the beginning and after 30 days of treatment. The Effective and Double doses of the drug reduced Total cholesterol along with levels of Triglycerides, Low density lipoprotein and Very low density lipoprotein levels significantly (p < 0.01) along with a significant (p < 0.01) increase in high density lipoproteins (HDL) in rats. There was also significant (p < 0.01) improvement in atherogenic indices like Castelli Risk Index I, Non HDL C/HDL, Castelli risk Index II, TG/HDL, Atherogenic coefficient and Atherogenic Index of Plasma. The combination of powdered sprouted mung bean and yam powder have excellent lipid lowering potential.  相似文献   
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Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4 + T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.  相似文献   
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骨形成蛋白-9(BMP-9)是从胚胎鼠的肝脏c DNA文库中克隆得到的新型细胞因子,属于转化生长因子β超家族的成员,由肝脏非实质细胞合成分泌,在体内以类激素的形式发挥广泛的生物学作用。BMP-9不仅具有强烈的骨诱导活性,促进成骨细胞分化,还可通过调控糖代谢过程中关键酶的表达、促进胰岛素合成及分泌、增加胰岛素敏感性等方式调节体内葡萄糖平衡。本文主要对BMP-9与骨代谢及糖代谢的关系进行综述,为深入认识糖尿病、代谢性骨病及糖尿病性骨质疏松的发生机理提供理论依据,为糖尿病和骨骼疾病的防治提供新的思路。  相似文献   
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Bar-built estuaries are generally found at the mouths of smaller watersheds with seasonal precipitation, episodic streamflow and seasonal swell dynamics. Low streamflows and constructive wave forces form a sand bar at the mouth isolating the stream from the ocean, creating a ponded lagoon, and inundating the surrounding marsh plain. Bar-built estuaries are wide spread in California comprising over 50 percent of California's more than 500 estuaries. By connecting terrestrial, freshwater, and marine realms bar-built estuaries are complex and dynamic providing great habitat and ecosystem services. California has suffered some of the highest losses of wetland habitats, and the wetland habitats of bar-built estuaries continue to be threatened by further development, pollution, and climate related changes including diminished streamflows and sea level rise. Given this loss and threat we developed a California Rapid Assessment Method (CRAM) to assess the condition of California's bar-built estuaries. CRAM uses visual indicators to accurately reflect current wetland condition with regards to buffer habitat, hydrology, physical complexity, plant diversity and structure, and landscape influences. Here we validate this method by comparing results of CRAM for bar-built estuaries to other accepted measures of wetland condition that we simultaneously collected with CRAM including vegetative surveys, water nutrient levels, and GIS landscape scale measures of stress for 32 sites throughout California. CRAM correlated well with each of these three independent methods of assessing condition. Notably, the Environmental Monitoring and Assessment Program (EMAP) number of natives metric significantly correlated with CRAM Index and all Attribute scores. The strong correlations of CRAM to nutrient levels is particularly important considering the documentation of the negative impact of nutrients on fish populations, the use of bar-built estuaries by juveniles of commercially important species, and the nursery role of bar-built estuaries for maintaining imperiled populations of species such as steelhead. GIS measured percent impervious, percent agriculture, and percent dams all correlated well with expected CRAM Attribute scores at appropriate watershed scales relative to the area of inference for each CRAM metric. Further, CRAM for bar-built estuaries works well throughout California's diversity of environmental conditions and regardless of geography, timing, or whether the bar was open or closed during the survey. We hope that the availability of CRAM combined with available data repositories will enable local, state, and federal decision makers to better manage, restore, and conserve valuable bar-built estuaries in the face of continual threats like development, drought, and sea level rise.  相似文献   
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Nbp35 and Cfd1 are prototypical members of the MRP/Nbp35 class of iron-sulfur (FeS) cluster scaffolds that function to assemble nascent FeS clusters for transfer to FeS-requiring enzymes. Both proteins contain a conserved NTPase domain that genetic studies have demonstrated is essential for their cluster assembly activity inside the cell. It was recently reported that these proteins possess no or very low nucleotide hydrolysis activity in vitro, and thus the role of the NTPase domain in cluster biogenesis has remained uncertain. We have reexamined the NTPase activity of Nbp35, Cfd1, and their complex. Using in vitro assays and site-directed mutagenesis, we demonstrate that the Nbp35 homodimer and the Nbp35-Cfd1 heterodimer are ATPases, whereas the Cfd1 homodimer exhibited no or very low ATPase activity. We ruled out the possibility that the observed ATP hydrolysis activity might result from a contaminating ATPase by showing that mutation of key active site residues reduced activity to background levels. Finally, we demonstrate that the fluorescent ATP analog 2′/3′-O-(N′-methylanthraniloyl)-ATP (mantATP) binds stoichiometrically to Nbp35 with a KD = 15.6 μm and that an Nbp35 mutant deficient in ATP hydrolysis activity also displays an increased KD for mantATP. Together, our results demonstrate that the cytosolic iron-sulfur cluster assembly scaffold is an ATPase and pave the way for interrogating the role of nucleotide hydrolysis in cluster biogenesis by this large family of cluster scaffolding proteins found across all domains of life.  相似文献   
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The relationship between cellular metabolism and the cell cycle machinery is by no means unidirectional. The ability of a cell to enter the cell cycle critically depends on the availability of metabolites. Conversely, the cell cycle machinery commits to regulating metabolic networks in order to support cell survival and proliferation. In this review, we will give an account of how the cell cycle machinery and metabolism are interconnected. Acquiring information on how communication takes place among metabolic signaling networks and the cell cycle controllers is crucial to increase our understanding of the deregulation thereof in disease, including cancer.  相似文献   
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