NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content.

In mature neurons, postsynaptic N-methyl-D-aspartate receptors (NMDARs) are segregated into two populations, synaptic and extrasynaptic, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content. Here, we identify the phosphorylation of the PDZ-ligand of the GluN2B subunit of NMDARs (at S1480) as a critical determinant in dynamically controlling NMDAR synaptic content. We find that phosphorylation of GluN2B at S1480 maintains NMDARs at extrasynaptic membranes as part of a protein complex containing protein phosphatase 1 (PP1). Global activation of NMDARs leads to the activation of PP1, which mediates dephosphorylation of GluN2B at S1480 to promote an increase in synaptic NMDAR content. Thus, PP1-mediated dephosphorylation of the GluN2B PDZ-ligand modulates the synaptic expression of NMDARs in mature neurons in an activity-dependent manner, a process with profound consequences for synaptic and structural plasticity, metaplasticity, and synaptic neurotransmission

Education as inefficient resource against depressive symptoms in the Czech Republic: Cross-sectional analysis of the HAPIEE study

Background: Increasing educational level of the population could be a strategy to prevent depression. We investigated whether education may offer a greater benefit for mental health to women and to individuals living in socioeconomically disadvantaged areas. Methods: We performed a cross-sectional study using data on 6964 Czech participants of the Health, Alcohol and Psychosocial factors in Eastern Europe study (on average 58 years old; 53% women). Binary logistic regression was used to examine the association of education with depressive symptoms, adjusting for several groups of covariates. Interactions were tested between education and sex as well as between education and socioeconomic advantage of the area of residence. Results: Higher education was strongly associated with lower odds of depressive symptoms, independently of sociodemographic characteristics, health behavior and somatic diseases. This association was attenuated after adjusting for other markers of individual socioeconomic position (work activity, material deprivation and household items). There were no interactions between education and either sex or socioeconomic advantage of the area of residence. Conclusions: We did not find an independent association between education and depressive symptoms after controlling for other socioeconomic markers in a sample with a formative history of communistic ideologies. Women or individuals from socioeconomically disadvantaged areas do not seem to gain a larger mental health benefit from education

P53 binds preferentially to non-B DNA structures formed by the pyrimidine-rich strands of GaA·TTC trinucleotide repeats associated with Friedreich’s ataxia

Expansions of trinucleotide repeats (TNRs) are associated with genetic disorders such as Friedreich’s ataxia. The tumor suppressor p53 is a central regulator of cell fate in response to different types of insults. Sequence and structure-selective modes of DNA recognition are among the main attributes of p53 protein. The focus of this work was analysis of the p53 structure-selective recognition of TNRs associated with human neurodegenerative diseases. Here, we studied binding of full length p53 and several deletion variants to TNRs folded into DNA hairpins or loops. We demonstrate that p53 binds to all studied non-B DNA structures, with a preference for non-B DNA structures formed by pyrimidine (Py) rich strands. Using deletion mutants, we determined the C-terminal DNA binding domain of p53 to be crucial for recognition of such non-B DNA structures. We also observed that p53 in vitro prefers binding to the Py-rich strand over the purine (Pu) rich strand in non-B DNA substrates formed by sequence derived from the first intron of the frataxin gene. The binding of p53 to this region was confirmed using chromatin immunoprecipitation in human Friedreich’s ataxia fibroblast and adenocarcinoma cells. Altogether these observations provide further evidence that p53 binds to TNRs’ non-B DNA structures

THE RAMAN SPECTROSCOPY USE FOR MONITORING OF CHANGES IN THE GLASS STRUCTURE OF THE THIN LAYERS CAUSED BY ION IMPLANTATION

In this paper, we have demonstrated the utility of Raman spectroscopy as a technique for the characterisation of changes in the glass structure of the thin layers caused by ion implantation. Various types of silicate glasses were implanted by Au+ ions with energy of 1.7 MeV and a fluence of 1 x 1016 ions.cm-2 to create gold nanoparticles in thin sub-surface layer of the glass. It was proved that the structure of the glass has an indisputable impact on the extent of depolymerisation of the glass network after implantation. It was shown that the degree of glass matrix depolymerisation can be described using the evaluation of Qn factors in the implanted layers from different depths. After analysis of Raman spectra, the relation between nucleation and the resulting parameters of the gold nanoparticles was put into connection with the feasibility of the glass to recover its structure during post-implantation annealing. Also the creation of new bonds in the glass network was discussed

Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation

Introduction: The disposition of drugs is potentially changed due to extracorporeal membrane oxygenation (ECMO) in neonates and infants. Methods: The aim of the study was to evaluate the individual pharmacokinetics (PK) of phenobarbital and the effect of PK covariates in neonates and infants undergoing ECMO. Sixteen patients (7 neonates, 9 infants) treated with phenobarbital during ECMO (centrifugal-flow pump circuits) were enrolled in the PK study. Phenobarbital serum concentrations were measured using a fluorescence polarization immunoassay. Individual PK parameters - volume of distribution (Vd) and clearance (CL) were calculated in a one-compartmental pharmacokinetic model. Results: The mean (SD) Vd and CL values in neonates were 0.46 (0.24) L/kg and 8.0 (4.5) mL/h/kg, respectively. Respective values in infants were 0.56 (0.23) L/kg and 8.5 (3.1) mL/h/kg. PK parameters in neonates and infants were not significantly different. We observed high inter-individual variability in PK parameters (coefficients of variation [CV] were 52% and 53% for CL and Vd, respectively). Doses were adjusted based on therapeutic drug monitoring (TDM) in 87.5% patients. Only 50% of the first measured phenobarbital serum concentrations in each patient were within the therapeutic range of 10-40 mg/L, in comparison with 88.6% concentration measured after TDM implementation. Linear regression models showed that both Vd and CL are significantly related with body weight (BW) and length. Median optimal phenobarbital loading dose (LD) and maintenance dose (MD), calculated from pharmacokinetic data, were 15 mg/kg and 4 mg/kg/day, respectively. Conclusions: Body weight was shown to be the main PK covariate of phenobarbital disposition. Subsequent dosing nomograms are provided for phenobarbital dosing during ECMO

Insulation effects of Icelandic dust and volcanic ash on snow and ice

In the Arctic region, Iceland is an important source of dust due to ash production from volcanic eruptions. In addition, dust is resuspended from the surface into the atmosphere as several dust storms occur each year. During volcanic eruptions and dust storms, material is deposited on the glaciers where it influences their energy balance. The effects of deposited volcanic ash on ice and snow melt were examined using laboratory and outdoor experiments. These experiments were made during the snow melt period using two different ash grain sizes (1 phi and 3.5 phi) from the Eyjafjallajokull 2010 eruption, collected on the glacier. Different amounts of ash were deposited on snow or ice, after which the snow properties and melt were measured. The results show that a thin ash layer increases the snow and ice melt but an ash layer exceeding a certain critical thickness caused insulation. Ash with 1 phi in grain size insulated the ice below at a thickness of 9-15 mm. For the 3.5 phi grain size, the insulation thickness is 13 mm. The maximum melt occurred at a thickness of 1 mm for the 1 phi and only 1-2 mm for 3.5 phi ash. A map of dust concentrations on Vatnajokull that represents the dust deposition during the summer of 2013 is presented with concentrations ranging from 0.2 up to 16.6 g m(-2).Peer reviewe

Synthesis of ‘unfeasible’ zeolites

R.E.M. thanks the Royal Society and the E.P.S.R.C. (Grants EP/L014475/1, EP/K025112/1 and EP/K005499/1) for funding work in this area. J.Č. and P.N. acknowledge the Czech Science Foundation for the project of the Centre of Excellence (P106/12/G015) and the European Union Seventh Framework Programme (FP7/ 2007-­‐2013) under grant agreement n°604307. The research leading to these results has received funding from the European Union Seventh Framework Programme under Grant Agreement 312483 – ESTEEM2 (Integrated Infrastructure Initiative–I3). We thank Professor Wuzong Zhou and Dr. Fengjiao Yu for their expertise in TEM and Daniel Dawson for help with NMR.Zeolites are porous aluminosilicate materials that have found applications in many different technologies. However, although simulations suggest that there are millions of possible zeolite topologies, only a little over 200 zeolite frameworks of all compositions are currently known, of which about 50 are pure silica materials. This is known as the zeolite conundrum - why have only so few of all the possible structures been made? Several criteria have been formulated to explain why most zeolites are unfeasible synthesis targets. Here we demonstrate the synthesis of two such 'unfeasible' zeolites, IPC-9 and IPC-10, through the assembly-disassembly-organization-reassembly mechanism. These new high-silica zeolites have rare characteristics, such as windows that comprise odd-membered rings. Their synthesis opens up the possibility of preparing other zeolites that have not been accessible by traditional solvothermal synthetic methods. We envisage that these findings may lead to a step change in the number and types of zeolites available for future applications.PostprintPeer reviewe

CircumMed+Euro pine forest database: an electronic archive for Mediterranean and European forests

Large thematic databases of vegetation-plots are increasingly needed for vegetation studies and biodiversity research. In this paper, we present the CircumMed+Euro Pine Forest Database (GIVD ID: EU-00-026), which in September 2018 encompassed 5590 records from pine-dominated vegetation plots (relevés) and associated vegetation types from 23 countries of temperate Europe, Eastern Mediterranean and North Africa. These vegetation plots were collected through a detailed literature search for plots not included in the European Vegetation Archive (EVA). The database includes plots from 192 bibliographic references and unpublished vegetation plots by different authors. All vegetation plots are georeferenced, and coordinates are available with different accuracy as reported by the authors. The database is managed by the Vegetation Science Group, Department of Botany and Zoology of the Masaryk University in Brno (Czech Republic). It is registered in the Global Index of Vegetation-Plot Databases (GIVD) with the code EU-00-026 and is accessible through the European Vegetation Archive (EVA) or by asking the Custodian. The CircumMed+Euro Pine Forest Database is an important resource for conducting different types of broad-scale studies in the fields of vegetation classification, plant invasion ecology, macroecology and biological conservationN/

Psychology of Fragrance Use: Perception of Individual Odor and Perfume Blends Reveals a Mechanism for Idiosyncratic Effects on Fragrance Choice

Cross-culturally, fragrances are used to modulate body odor, but the psychology of fragrance choice has been largely overlooked. The prevalent view is that fragrances mask an individual's body odor and improve its pleasantness. In two experiments, we found positive effects of perfume on body odor perception. Importantly, however, this was modulated by significant interactions with individual odor donors. Fragrances thus appear to interact with body odor, creating an individually-specific odor mixture. In a third experiment, the odor mixture of an individual's body odor and their preferred perfume was perceived as more pleasant than a blend of the same body odor with a randomly-allocated perfume, even when there was no difference in pleasantness between the perfumes. This indicates that fragrance use extends beyond simple masking effects and that people choose perfumes that interact well with their own odor. Our results provide an explanation for the highly individual nature of perfume choice