125,496 research outputs found
Molecular basis of ligand binding and receptor activation in the oxytocin and vasopressin receptor family
No full textAlthough it is now widely accepted that G-protein-coupled receptors exist in at least two allosteric states, inactive and active, and that the spontaneous equilibrium between the two is regulated by various events including the binding of specific agonists and antagonists, the molecular counterparts of these functionally different states are still poorly understood. In this paper, we review our current knowledge concerning the structure-function relationships of the oxytocin and vasopressin receptors, focusing in particular on the process of receptor activation. Using a combined approach of site-directed mutagenesis and molecular modelling, we investigated the molecular events leading to agonist-dependent and -independent receptor activation in the human oxytocin receptor. Our analysis allows us to propose that the active conformations of this receptor are characterised by similar rearrangements of its cytosolic regions that ultimately lead to the opening of a putative docking site for the G-protein. Furthermore, the dynamics of these motions are similar to that observed in the alpha1B-adrenergic receptor, thus suggesting that, although activated by different ligands, the process of receptor isomerization in these two receptors is regulated by the same cluster of highly conserved residues and that common molecular events are responsible for receptor activation in different G-protein-coupled receptors
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Further insights into platinum carbonyl Chini clusters
No full textThe oxidation of [Ph3P(CH2)12PPh3][Pt15(CO)30] with CF3COOH in THF afforded [Ph3P(CH2)12PPh3][Pt18(CO)36] as a precipitate which was re-crystallized from dmf/isopropanol. This salt self-assembles in the solid state adopting an unprecedented morphology which consists of infinite chains of [Pt9(CO)18]− units. The solid state structure of [Ph3P(CH2)12PPh3][Pt18(CO)36] may be viewed as a snapshot in which [Pt9(CO)18]− units are approaching and ready to exchange outer Pt3(CO)6 fragments. The reactions of Chini clusters with isonitriles proceed via redox-fragmentation, at difference with those involving phosphines that may occur both via non-redox substitution and redox fragmentation, depending on the experimental conditions. Thus, the reaction of [Pt6(CO)12]2− with CNXyl afforded Pt5(CNXyl)10, whereas Pt9(CNXyl)13(CO) was obtained from the reaction of [Pt15(CO)30]2− with CNXyl. These two new neutral clusters have been structurally characterized as their Pt5(CNXyl)10·2toluene and Pt9(CNXyl)13(CO)·solv solvates. DFT studies on the CO exchange of [Pt6(CO)12]2− suggest an associative interchange mechanism, which may be extended also to larger Chini clusters and the initial steps of their reactions with other soft nucleophiles
Oxytocin stimulates migration and invasion in human endothelial cells
No full textBackground and purpose. It has recently been reported that oxytocin (OT) is produced by some tumoral cell types, and that OT receptors (OTRs) belonging to the G protein-coupled receptor (GPCR) family are expressed in a variety of cell types. Among these, human umbilical vein endothelial cells (HUVECs) respond to OT with an increased proliferation, suggesting a possible role for the hormone in the regulation of angiogenesis. Experimental approach. We employed chemotaxis and chemoinvasion assays to characterize the effect of OT on HUVEC motility, and immunoblot analysis to study its molecular mechanisms of action. Key results. We showed that OT stimulates migration and invasion in HUVECs via OTR activation. Searching for the molecular mechanism(s) responsible for OT’s pro-migratory effect, we identified the Gq coupling of OTRs and phospholipase C (PLC) as the main effectors of OT’s action in HUVECs. We also found that OT stimulates the phosphorylation of endothelial nitric oxide synthase (eNOS) via the phosphatidylinositol-3-kinase (PI-3-K)/AKT pathway, and that the activation of PI-3-K and formation of nitric oxide (NO) are required for the pro-migratory effect of OT. Conclusions and implications. The ability of OT to stimulate HUVEC motility and invasion suggests that the hormone can participate to physiopathological processes where activation of endothelial cells plays an important role, like for example angiogenesis. Interestingly, both the AKT and eNOS phosphorylation induced by OTR activation depend on PLC activity, thus suggesting the existence of a still undefined mechanism connecting PLC to the PI-3-K/AKT pathway upon OT stimulation
Heterometallic Ni-Pt Chini-Type Carbonyl Clusters: An Example of Molecular Random Alloy Clusters
No full textThe direct reactions of homometallic [Ni6(CO)12]2- and [Pt6(CO)12]2- Chini carbonyl clusters result in heterometallic Ni-Pt Chini-type clusters of the general formula [Pt6-xNix(CO)12]2- (x = 0-6). Their molecular structures have been determined by single-crystal X-ray diffraction (SC-XRD), showing a common octahedral (staggered, D3d) structure analogous to that of [Ni6(CO)12]2-, whereas [Pt6(CO)12]2- displays a trigonal-prismatic (eclipsed, D3h) structure. This structural change after replacing one single Pt with Ni may be classified as an alloying effect, and it has been theoretically investigated by DFT methods. Spectroscopic (IR and 195Pt and 13C NMR) and ESI-MS studies indicate that mixtures of [Pt6-xNix(CO)12]2- (x = 0-6) clusters are actually present in solution, whose compositions may be varied in an almost continuous way. Thus, they may be viewed as random alloy clusters whose overall compositions depend on the stoichiometry of the reagents
Multi-Physics Modeling and Finite Element Approximation of Charge Flow in Ionic Channels
No full textOxytocin receptor signaling in myoepithelial and cancer cells
No full textOxytocin (OT) plays a crucial role as a mediator of breast myoepithelial cell contraction, the process responsible for the ejection of milk during lactation, and is also involved in myoepithelial cell proliferation and postpartum mammary gland proliferation. Furthermore, although a number of breast cancer cells have oxytocin receptors (OTRs), it has been reported that OT stimulates, inhibits, or has no effect on cell proliferation. As these different effects seem to be mediated by different signaling pathways elicited by OTR stimulation, we here review the regulation of OTR signaling in different cell systems and discuss how understanding the molecular basis of receptor coupling specificity has become extremely important for understanding the role played by OTRs in regulating cell growth
- …
