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1.
Regulatory effects of the saturated fatty acids 6:0 through 18:0 on hepatic low density lipoprotein receptor activity in the hamster.
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The plasma concentration of cholesterol carried in low density lipoproteins is principally determined by the level of LDL receptor activity (Jm) and the LDL-cholesterol production rate (Jt) found in animals or man. This study delineates which saturated fatty acids alter Jm and Jt and so increase the plasma LDL-cholesterol level. Jm and Jt were measured in vivo in hamsters fed a constant level of added dietary cholesterol (0.12%) and triacylglycerol (10%), where the triacylglycerol contained only a single saturated fatty acid varying in chain length from 6 to 18 carbon atoms. After feeding for 30 d, the 12:0, 14:0, 16:0, and 18:0 fatty acids, but not the 6:0, 8:0, and 10:0 compounds, became significantly enriched in the liver total lipid fraction of the respective groups fed these fatty acids. However, only the 12:0, 14:0, and 16:0 fatty acids, but not the 6:0, 8:0, 10:0, and 18:0 compounds, suppressed Jm, increased Jt, and essentially doubled plasma LDL-cholesterol concentrations. Neither the 16:0 nor 18:0 compound altered rates of cholesterol synthesis in the extrahepatic organs, and both lowered the hepatic total cholesterol pool. Thus, the different effects of the 16:0 and 18:0 fatty acids could not be attributed to a difference in cholesterol delivery to the liver. Since these changes in LDL kinetics took place without an apparent alteration in external sterol balance, the regulatory effects of the 12:0, 14:0, and 16:0 fatty acids presumably are mediated through some change in a putative intrahepatic regulatory pool of sterol in the liver. 相似文献
2.
Aline S. Hora Sueli A. Taniwaki Nathana B. Martins Nataly N.R. Pinto Andr E. Schlemper Andr L.Q. Santos Matias P.J. Szab Paulo E. Brando 《Emerging infectious diseases》2021,27(4):1177
We obtained the complete sequence of a novel poxvirus, tentatively named Brazilian porcupinepox virus, from a wild porcupine (Coendou prehensilis) in Brazil that had skin and internal lesions characteristic of poxvirus infection. The impact of this lethal poxvirus on the survival of this species and its potential zoonotic importance remain to be investigated. 相似文献
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Dizon J Reiffel J Kassotis J Woollett I Garan H 《Journal of cardiovascular electrophysiology》2003,14(5):461-466
INTRODUCTION: Despite the great success in treating AV nodal reentrant tachycardia (AVNRT) with radiofrequency modification of the AV node, the dimensions of the electrophysiologic circuit of this arrhythmia remain unclear, and simple models fail to explain all tachycardia-related phenomena. METHODS AND RESULTS: We describe three unusual cases of supraventricular tachycardia (SVT). In all three cases, retrograde atrial activation during ventricular pacing or during SVT manifested local left atrial electrograms recorded from the coronary sinus preceding the septal atrial electrograms (eccentric activation), with earliest atrial activity at the lateral or posterolateral mitral annulus. Electrophysiologic maneuvers and observations were consistent with AVNRT as the mechanism in each case. In all cases, radiofrequency modification of the AV node eliminated inducible SVT and abolished dual pathway AV nodal physiology. The retrograde atrial activation sequence during ventricular pacing changed after ablation in each case, with septal atrial electrograms preceding left atrial electrograms recorded from the coronary sinus (concentric activation). CONCLUSION: The observations in these cases cannot be explained by the traditional model of slow, fast, and intermediate AV nodal pathways. A model incorporating a circuit close to the AV node with left atrial and coronary sinus connections is proposed. 相似文献
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Fatty acids regulate hepatic low density lipoprotein receptor activity through redistribution of intracellular cholesterol pools.
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C M Daumerie L A Woollett J M Dietschy 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(22):10797-10801
When the intake of dietary cholesterol in the hamster is constant, feeding the saturated 14:0 fatty acid (n-tetradecanoic acid) elevates the plasma low density lipoprotein (LDL) cholesterol concentration from 72 to 204 mg/dl, while the monounsaturated 18:1 fatty acid (cis-9-octadecenoic acid) lowers this level to 28 mg/dl. The 14:0 fatty acid lowers the hepatic cholesteryl ester concentration from 12 to 5 mg/g, while the abundance of this fatty acid in the ester fraction is increased 13-fold. Hepatic LDL receptor activity is depressed to 41% of control, while the LDL cholesterol production rate is increased to 132%. These changes account for the 3-fold increase in the plasma LDL cholesterol concentration. In contrast, feeding the 18:1 fatty acid increases hepatic cholesteryl ester concentration to 21 mg/g, and the abundance of this acid in the esters is increased 1.4-fold. Hepatic receptor activity is increased to 145%, while the production rate is suppressed to 68% of control. These changes account for the decrease in plasma LDL cholesterol level to 28 mg/dl. Despite these marked changes in LDL metabolism, however, the 14:0 and 18:1 fatty acids cause no change in net cholesterol balance across the liver. These results suggest that there are two fundamentally different mechanisms regulating hepatic LDL metabolism. One involves changes in net sterol balance across the liver brought about by alterations in the rate of cholesterol or bile acid absorption across the intestine, while the second is articulated through a redistribution of the putative sterol regulatory pool within the hepatocyte that is dictated by the type of long-chain fatty acid that reaches the liver. 相似文献
10.
Yuanming Liu Hong-Ling Cai Matthew Zelisko Yunjie Wang Jinglan Sun Fei Yan Feiyue Ma Peiqi Wang Qian Nataly Chen Hairong Zheng Xiangjian Meng Pradeep Sharma Yanhang Zhang Jiangyu Li 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(27):E2780-E2786
Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 μC/cm2, whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications.Ferroelectricity was first discovered in synthetic materials in 1920 when spontaneous polarization of Rochelle salt was found to be switchable by an external electric field (1). Ferroelectrics thus belongs to a larger class of pyroelectric materials that possess a unique polar axis, which, in turn, belongs to piezoelectrics exhibiting linear coupling between electric and mechanical fields (2). Because of these versatile properties, ferroelectric materials are promising for a wide range of technological applications in data storage, sensing, actuation, energy harvesting, and electro-optic devices (3). Biological tissues, such as bones and tendons, were first observed to be piezoelectric in 1950s (4), and shortly thereafter, pyroelectricity was discovered in a variety of biological materials as well (5, 6). Ever since then, ferroelectricity has been speculated for biological systems, and its potential physiological significance has been suggested (7). For example, it was hypothesized that the conformation transition in voltage-gated ion channels is ferroelectric in nature (8, 9). Nevertheless, indication of ferroelectricity in biological materials has only recently emerged from nanoscale piezoresponse force microscopy (PFM) studies (10–13).This work is motivated by our recent observation of PFM switching in elastin (12), which has generated quite a bit of excitement, although there is still considerable skepticism regarding the notion of biological ferroelectricity. Such reservation is understandable, given the unusual phenomenon of ferroelectric switching in biology, some ambiguities associated with PFM hysteresis, and a current lack of understanding of the basic science underpinning the switching mechanism. Indeed, there is neither macroscopic evidence of ferroelectric switching nor microscopic understanding of its molecular origin. The current work seeks to address these aforementioned issues, and thus to advance our understanding of biological ferroelectricity on two important fronts. First, we present macroscopic observation of ferroelectric switching in a biological system, derived from careful pyroelectric measurement. This dataset, in our view, decisively settles the long-standing question regarding ferroelectricity in biology. Furthermore, in close conjunction with experiments, we present a molecular-based computational study to elucidate the origin and mechanism underpinning ferroelectric switching of elastin. We show that the polarization in elastin is intrinsic at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics. Our findings thus establish ferroelectricity as an important biophysical property of proteins, and we believe this is a critical first step toward resolving its physiological significance and pathological implications. 相似文献