1,721,040 research outputs found
Facts about fats: New insights into the role of lipids in metabolism, disease and therapy
No full textAlthough initially regarded as a passive system to store energy, lipids are now considered to play crucial, structural and functional roles in almost all the biological processes involved in the regulation of physiological and pathological conditions [...]
Impact of sex and age on the mevalonate pathway in the brain: A focus on effects induced by maternal exposure to exogenous compounds
No full textThe mevalonate pathway produces cholesterol and other compounds crucial for numerous cellular processes. It is well known that age and sex modulate this pathway in the liver. Recently, similar effects were also noted in different brain areas, suggesting that alterations of the mevalonate pathway are at the root of marked sex-specific disparities in some neurodevelopmental disorders related to disturbed cholesterol homeostasis. Here, we show how the mevalonate pathway is modulated in a sex-, age-and region-specific manner, and how maternal exposure to exogenous compounds can disturb the regulation of this pathway in the brain, possibly inducing functional alterations
Regulation and deregulation of cholesterol homeostasis: the liver as metabolic “power station”
No full textCholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumulation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations could lead to several life-threatening pathologies such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification, degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins (SREBPs) that are responsable for the maintenance of cholesterol homeostasis through an intricated mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis could be esterified and incorporated into apolipoprotein B (ApoB)-100-containing very low density lipoproteins (VLDL), which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDLs particles are internalized in the liver interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview on liver cholesterol metabolism regulation and deregulation and on the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological treatment and novel hypocholesterolemic strategies will also be introduced
Cholesterol Homeostasis Failure in the Brain: Implications for Synaptic Dysfunction and Cognitive Decline.
No full textCholesterol is one of the most important molecules in cell physiology because of its involvement in several biological processes: for instance, it determines both physical and biochemical properties of cell membranes and proteins. Disruption to cholesterol homeostasis leads to coronary heart disease, atherosclerosis and metabolic syndrome. Strong evidence suggests that cholesterol also has a crucial role in the brain as various neurological and neurodegenerative disorders, including Alzheimer's, Huntington's and Parkinson diseases are associated with disruptions to cholesterol homeostasis. Here, we summarize the current knowledge about the role cholesterol plays at synaptic junctions and the pathological consequences caused by disruptions in the homeostatic maintenance of this compound
Limitations to Electrical Probing of Spontaneous Polarization in Ferroelectric-Dielectric Heterostructures
Full text linkAn accurate estimate of the ferroelectric polarization in ferroelectric-dielectric stacks is important from a materials science perspective, and it is also crucial for the development of ferroelectric based electron devices. This paper revisits the theory and application of the PUND technique in Metal-Ferroelectric-Dielectric-Metal (MFDM) structures by using analytical derivations and numerical simulations. In an MFDM structure the results of the PUND technique may largely differ from the polarization actually switched in the stack, which in turn is different from the remnant polarization of the underlying ferroelectric. The main hindrances that prevent PUND measurements from providing a good estimate of the polarization switching in MFDM stacks are thus discussed. The inspection of the involved physical quantities, not always accessible in experiments, provides a useful insight about the main sources of the errors in the PUND technique, and clarifies the delicate interplay between the depolarization field and the charge injection and trapping in MFDM stacks with a thin dielectric layer
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Modelling and Simulations of Ferroelectric Materials and Ferroelectric-Based Nanoelectronic Devices : (Invited Paper)
No full textThis paper provides a brief introduction to the phenomenological aspects of the polarization in ferrroelectric materials, and then an analysis of a few selected topics related to the modelling of ferroelectrics. The description of ferroelectric-based devices is quite challenging, particularly because the ferroelectric is frequently stacked with other dielectrics or with a semiconductor, as opposed to being placed between metal electrodes. Predictive modelling of ferroelectric devices is admittedly difficult, and thus the scrutiny and calibration of the models by comparison to sound experimental data is of paramount importance
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