Integrated Regulation of Signal Coding and Plasticity by NMDA Receptors at a Central Synapse

The role of NMDA and non-NMDA glutamate receptors in long-term potentiation has been intensely investigated, yet recent evidence on the dynamics of synaptic depolarization suggests that the original view should be extended. NMDA receptor-mediated currents, apart from their Ca2+ permeability, show a marked voltage dependence, consisting of current increase and slowdown during membrane depolarization. During highfrequency synaptic transmission, NMDA current increase and slowdown are primed by non-NMDA receptor-dependent depolarization and proceed regeneratively. Thus, NMDA receptors make a decisive contribution to membrane depolarization and spike-firing. From the data obtained at the mossy fiber- granule cell synapse of the cerebellum, we propose that the electrogenic role of NMDA receptors is functional to LTP induction. Moreover, during LTP, both NMDA and non- NMDA receptor currents are potentiated, thus establishing a feed-forward mechanism that ultimately enhances spike firing. Thus, NMDA receptors exert an integrated control on signal coding and plasticity. This mechanism may have important implications for information processing at the cerebellar mossy fibergranule cell relay

Visualization in mixed-methods research on social networks

Introduction to edited special section of Sociological Research Onlin

P K-Edge XANES Calculations of Mineral Standards: Exploring the Potential of Theoretical Methods in the Analysis of Phosphorus Speciation

Phosphorus K-edge X-ray absorption near-edge structure(XANES)spectroscopy is a technique routinely employed in the qualitativeand quantitative analysis of phosphorus speciation in many scientificfields. The data analysis is, however, often performed in a qualitativemanner, relying on linear combination fitting protocols or simplecomparisons between the experimental data and the spectra of standards,and little quantitative structural and electronic information is thusretrieved. Herein, we report a thorough theoretical investigationof P K-edge XANES spectra of NaH2PO4 & BULL;H2O, AlPO4, & alpha;-Ti(HPO4)(2)& BULL;H2O, and FePO4 & BULL;2H(2)O showingexcellent agreement with the experimental data. We find that differentcoordination shells of phosphorus, up to a distance of 5-6 & ANGS; from the photoabsorber, contribute to distinct features inthe XANES spectra. This high structural sensitivity enables P K-edgeXANES spectroscopy to even distinguish between nearly isostructuralcrystal phases of the same compound. Additionally, we provide a rationalizationof the pre-edge transitions observed in the spectra of & alpha;-Ti(HPO4)(2)& BULL;H2O and FePO4 & BULL;2H(2)O through density of states calculations. These pre-edge transitionsare found to be enabled by the covalent mixing of phosphorus s andp orbitals and titanium or iron d orbitals, which happens even thoughneither metal ion is directly bound to phosphorus in the two systems.Calculating a P K-edge XANES spectrumwith the FDMNES programstarting from a crystallographic structure leads to excellent agreementwith the experimental data and DOS calculations that enable accurateinterpretation of the observed transitions

Corticosteroid switch after progression on abiraterone acetate plus prednisone

Introduction: Abiraterone acetate plus prednisone is approved in metastatic castration-resistant prostate cancer. There is some evidence in favour of the steroid switch from prednisone to dexamethasone in patients who progressed whilst on abiraterone acetate plus prednisone or prednisolone. Materials and Methods: The aim of this review is to discuss the results from the clinical studies available, examining potential mechanisms of action and patient selection criteria for this treatment option. Results: A total of four studies were evaluated. Among possible eligibility criteria for steroid switch, we found: PSA progression without any radiological or clinical progression during abiraterone acetate + prednisone; no high-grade adverse events related to CYP-17 inhibition; and unfitness for chemotherapy or radium-223. Conclusion: Although large randomized prospective trials are warranted, steroid switch seems to offer a good option for certain patients treated with abiraterone acetate plus prednisone or prednisolone

PPARs in Human Neuroepithelial Tumors: PPAR Ligands as Anticancer Therapies for the Most Common Human Neuroepithelial Tumors

Neuroepithelial tumors represent a heterogeneous class of human tumors including benignant and malignant tumors. The incidence of central nervous system neoplasms ranges from 3.8 to 5.1 cases per 100,000 in the population. Among malignant neuroepithelial tumors, with regard to PPAR ligands, the most extensively studied were tumors of astrocytic origin and neuroblastoma. PPARs are expressed in developing and adult neuroepithelial cells, even if with different localization and relative abundance. The majority of malignant neuroepithelial tumors have poor prognosis and do not respond to conventional therapeutic protocols, therefore, new therapeutic approaches are needed. Natural and synthetic PPAR ligands may represent a starting point for the formulation of new therapeutic approaches to be used as coadjuvants to the standard therapeutic protocols. This review will focus on the major studies dealing with PPAR expression in gliomas and neuroblastoma and the therapeutic implications of using PPAR agonists for the treatment of these neoplasms

Caught while Dissolving: Revealing the Interfacial Solvation of the Mg2+ Ions on the MgO Surface

Interfaces between water and materials are ubiquitous and are crucial in materials sciences and in biology, where investigating the interaction of water with the surface under ambient conditions is key to shedding light on the main processes occurring at the interface. Magnesium oxide is a popular model system to study the metal oxide-water interface, where, for sufficient water loadings, theoretical models have suggested that reconstructed surfaces involving hydrated Mg2+ metal ions may be energetically favored. In this work, by combining experimental and theoretical surface-selective ambient pressure X-ray absorption spectroscopy with multivariate curve resolution and molecular dynamics, we evidence in real time the occurrence of Mg2+ solvation at the interphase between MgO and solvating media such as water and methanol (MeOH). Further, we show that the Mg2+ surface ions undergo a reversible solvation process, we prove the dissolution/redeposition of the Mg2+ ions belonging to the MgO surface, and we demonstrate the formation of octahedral [Mg(H2O)6]2+ and [Mg(MeOH)6]2+ intermediate solvated species. The unique surface, electronic, and structural sensitivity of the developed technique may be beneficial to access often elusive properties of low-Z metal ion intermediates involved in interfacial processes of chemical and biological interest

Direct structural and mechanistic insights into fast bimolecular chemical reactions in solution through a coupled XAS/UV-Vis multivariate statistical analysis

In this work, we obtain detailed mechanistic and structural information on bimolecular chemical reactions occurring in solution on the second to millisecond time scales through the combination of a statistical, multivariate and theoretical analysis of time-resolved coupled X-ray Absorption Spectroscopy (XAS) and UV-Vis data. We apply this innovative method to investigate the sulfoxidation of p-cyanothioanisole and p-methoxythioanisole by the nonheme FeIV oxo complex [N4Py·FeIV(O)]2+ (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) in acetonitrile at room temperature. By employing statistical and multivariate techniques we determine the number of key chemical species involved along the reaction paths and derive spectral and concentration profiles for the reaction intermediates. From the quantitative analysis of the XAS spectra we obtain accurate structural information for all reaction intermediates and provide the first structural characterization in solution of complex [N4Py·FeIII(OH)]2+. The employed strategy is promising for the spectroscopic characterization of transient species formed in redox reactions. © The Royal Society of Chemistry