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Based on a theory of impulsive and reflective human behavior, we test the effects of transcranial direct current stimulation (tDCS) targeting either prefrontal or parietal cortex in either hemisphere. In a confirmatory registered report, cathodal tDCS is administered to conceptually reproduce tDCS modulations of implicit spatial-numerical associations, numerical distance effects, and response inhibition. Those cognitive operations are hypothesized to draw on left prefrontal, parietal, and right prefrontal activations, respectively, thereby susceptible to inhibitory, cathodal tDCS across those regions. Vice versa, the mutual regional and behavioral specificity of tDCS effects on these behavioral indices is examined and expected to produce double dissociations. In a mixed within-subjects (baseline, during tDCS, post-tDCS) and between-subjects (target electrode: left/right prefrontal cortex/posterior parietal cortex, or sham tDCS) design, we collect (a) confirmatory data on the robustness of cathodal tDCS effects on three behavioral effects and (b) differential data on the specificity of regional targets in male and female human participants. Results will provide crucial tests of theories of cortical organization implied by implicit associations and explicit regulation, which can direct future brain stimulation studies.

A major goal of education in elementary mathematics is the mastery of arithmetic operations. However, research on subtraction is rather scarce, probably because subtraction is often implicitly assumed to be cognitively similar to addition, its mathematical inverse. To evaluate this assumption, we examined the relation between the borrow effect in subtraction and the carry effect in addition, and the developmental trajectory of the borrow effect in children using a choice reaction paradigm in a longitudinal study. In contrast to the carry effect in adults, carry and borrow effects in children were found to be categorical rather than continuous. From grades 3 to 4, children became more proficient in two-digit subtraction in general, but not in performing the borrow operation in particular. Thus, we observed no specific developmental progress in place-value computation, but a general improvement in subtraction procedures. Statement of contribution What is already known on this subject? The borrow operation increases difficulty in two-digit subtraction in adults. The carry effect in addition, as the inverse operation of borrowing, comprises categorical and continuous processing characteristics. What does this study add? In contrast to the carry effect in adults, the borrow and carry effects are categorical in elementary school children. Children generally improve in subtraction performance from grades 3 to 4 but do not progress in place-value computation in particular.

The analysis of glycoproteins in body fluids represents a central task in the study of vital processes. Herein, we assessed the combined use of Concanavalin A and Wheat Germ Agglutinin as ligands to fractionate and enrich glycoproteins from oviductal fluid (OF), which is a source of molecules involved in fertilization. First, the selectivity was corroborated by a gel-based approach using glycoprotein staining and enzymatic deglycosylation. Nanoliquid chromatography-tandem mass spectrometry (nLC-ESI-MS/MS) further allowed the reliable identification of 134 nonbound as well as 130 lectin-bound OF proteins. Enrichment analysis revealed that 77% of the annotated proteins in the lectin-bound fraction were known glycoproteins (p-value [FDR] = 1.45E-31). The low variance of the number of peptide spectrum matches for each protein within replicates indicated a consistent reproducibility of the whole workflow (median CV 17.3% for technical replicates and 20.7% for biological replicates). Taken together, this study highlights the applicability of a lectin-based workflow for the comprehensive analysis of OF proteins and gives for the first time an insight into the broad glycoprotein content of OF.

Due to extraordinary properties and biocompatibility, diamond nanoparticles – nanodiamonds (NDs) are considered for various biomedical applications. Amongst other functional groups which may be grafted on the NDs surface, the amines (NHx) are highly demanded linkers for biomolecules and dyes. In this regard, a non-destructive, non-hazardous and low-cost method of NDs amination would further accelerate their industrial applications in biomedicine and life science. Here we present a study on NDs treatment using diffuse coplanar surface barrier discharge in the gas mixture H2:N2=1:1 at the atmospheric pressure. Detonation and high pressure–high temperature nanoparticles (D-NDs and HPHT-NDs) were used either as-received or air-annealed. The FTIR spectra confirmed the presence of N–H stretching vibrations for all kinds of NDs after the treatment. It was revealed by XPS and FTIR measurements that both kinds of D-NDs (as-received and air-annealed) exhibited higher content of -NH2 functions in the detected nitrogen groups than HPHT-NDs. The treatment of as-received D-NDs led to the conversion of -COOH groups to amides. A large increase of C–H bonds after the discharge treatment was found, especially for the annealed NDs forms. Raman spectroscopy revealed a decrease of sp2 carbon after the treatment of the as-received HPHT-NDs.

Two profoundly different carbon allotropes - nanocrystalline diamond and graphene - are of considerable interest from the viewpoint of a wide range of biomedical applications including implant coating, drug and gene delivery, cancer therapy, and biosensing. Osteoblast adhesion and proliferation on nanocrystalline diamond and graphene are compared under various conditions such as differences in wettability, topography, and the presence or absence of protein interlayers between cells and the substrate. The materials are characterized in detail by means of scanning electron microscopy, atomic force microscopy, photoelectron spectroscopy, Raman spectroscopy, and contact angle measurements. In vitro experiments have revealed a significantly higher degree of cell proliferation on graphene than on nanocrystalline diamond and a tissue culture polystyrene control material. Proliferation is promoted, in particular, by hydrophobic graphene with a large number of nanoscale wrinkles independent of the presence of a protein interlayer, i.e., substrate fouling is not a problematic issue in this respect. Nanowrinkled hydrophobic graphene, thus, exhibits superior characteristics for those biomedical applications where high cell proliferation is required under differing conditions.

The jet of reactive effluents produced by surface dielectric barrier discharge was used to deposit PEO-like plasma polymers from di(ethylene) glycol vinyl ether. The jet was confined within the hollow space of either circular cross-section with substrate placed perpendicular to the jet, or rectangular cross-section with the walls used as substrates. The best 67% retention of the ethers was obtained for the circular channel, whereas it was only 50% for the rectangular channel. In the latter case, deposition at longer distances was possible. In both cases, the deposition started with the formation of islands that grew, coalesced and eventually built up a continuous coating.

Rationale Mass spectrometry has shown itself to be the most efficient tool for the sequencing of peptides. However, de novo sequencing of novel natural peptides is significantly more challenging in comparison with the same procedure applied for the tryptic peptides. To reach the goal in this case it is essential to select the most efficient methods of triggering fragmentation and combine all the possible complementary techniques. Methods Collision-induced dissociation (CID), high-energy collision dissociation (HCD), and electron-transfer dissociation (ETD) tandem mass spectra recorded with a LTQ Orbitrap Velos instrument were used for the elucidation of the sequence of the natural non-tryptic peptides from the skin secretion of Rana latastei. Manual interpretation of the spectra was applied. Results The combined approach using CID, HCD, and ETD tandem mass spectra of the multiprotonated peptides in various charge states, as well as of their proteolytic fragments, allowed the sequences of seven novel peptides from the skin secretion of Rana latastei to be established. Conclusions Manual mass spectrometry sequencing of natural non-tryptic peptides from the skin secretion of Rana latastei provided the opportunity to work successfully with these species and demonstrated once again its advantage over automatic approaches. Copyright © 2015 John Wiley & Sons, Ltd.

Due to an extraordinary combination of intrinsic properties of diamond nanoparticles (DNPs), there is an increased demand for their usage in various areas. While a broad range of surface termination is often done by wet-chemical, UV-irradiation or plasma treatments, DNPs hydrogenation is still an open issue. Thermal annealing or microwave plasma treatment, both known as high-temperature processes, do not offer satisfactory solutions for DNPs hydrogenation. Here, we report on a new approach for plasma-assisted DNPs hydrogenation at temperatures below 100 °C. As-received detonation DNPs with size about 5 nm were annealed (oxidized) in air at 450 °C for 30 min to reduce non-diamond carbon content. Then the annealed DNPs were plasma treated using atmospheric-pressure diffuse coplanar surface barrier discharge in pure hydrogen at powers densities of 1.8 and 3.1 W/cm2. While infrared spectra of annealed DNPs were dominated by oxygen containing functional groups, plasma-hydrogenated DNPs revealed increase of bands of C-H stretching vibrations in the region of 2800-3000 cm-1 with only 5 min of plasma treatment. Prolonged plasma treatments up to 60 min resulted in the increase of C-H stretching vibrations and a decrease of C-O-C groups in the spectral region of 1000–1300 cm-1.

Novel experimental methods, including a modified single fiber in vitro motility assay, X-ray diffraction experiments, and mass spectrometry analyses, have been performed to unravel the molecular events underlying the aging-related impairment in human skeletal muscle function at the motor protein level. The effects of old age on the function of specific myosin isoforms extracted from single human muscle fiber segments, demonstrated a significant slowing of motility speed (P < 0.001) in old age in both type I and IIa myosin heavy chain (MyHC) isoforms. The force-generating capacity of the type I and IIa MyHC isoforms was, on the other hand, not affected by old age. Similar effects were also observed when the myosin molecules extracted from muscle fibers were exposed to oxidative stress. X-ray diffraction experiments did not show any myofilament lattice spacing changes, but unraveled a more disordered filament organization in old age as shown by the greater widths of the 1, 0 equatorial reflections. Mass spectrometry (MS) analyses revealed eight age-specific myosin post-translational modifications (PTMs), in which two were located in the motor domain (carbonylation of Pro79 and Asn81) and six in the tail region (carbonylation of Asp900, Asp904, and Arg908; methylation of Glu1166; deamidation of Gln1164 and Asn1168). However, PTMs in the motor domain were only observed in the IIx MyHC isoform, suggesting PTMs in the rod region contributed to the observed disordering of myosin filaments and the slowing of motility speed. Hence, interventions that would specifically target these PTMs are warranted to reverse myosin dysfunction in old age.

Nanocrystalline diamond (NCD) films may be used in biosensing after modification of their surfaces with active functional groups. Here, surface functionalization of O- and H-NCD films with amine groups was made by 2 plasma-based processes: a) RF plasma treatment in ammonia, b) the deposition of thin amine-containing plasma polymer via RF magnetron sputtering of nylon target in Ar/N2 mixture. Amination of the NCD films by plasma treatment in NH3 caused an attachment of 1% of primary amines but destroyed the surface conductivity of H-NCD films. The 5% concentration of NH2 was detected on the NCD covered with the plasma polymer. Moreover, the surface conductivity of H-NCD films reached 10−7 S.

RATIONALE: Mass spectrometry has shown itself as the most efficient tool for the sequencing of peptides. However, de novo sequencing of novel natural peptides is significantly more challenging in c ...

Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive car ...

A series of high quality FexGa1−xBO3 single crystals with 0 ≤ x ≤ 1 was prepared and studied by electron magnetic resonance in the temperature range from 4 to 290 K. At low x, only the electron paramagnetic resonance (EPR) of diluted Fe3+ ions is present. The EPR spectra for different orientations of the magnetizing field have been computer simulated. With a conventional spin Hamiltonian including the Zeeman and fine-structure terms, two different sets of best-fit parameters have been found. This ambiguity has been resolved on the basis of the general spin Hamiltonian with parameters determined from the crystallographic data using the Newman superposition model. A detailed fitting to the experimental EPR spectra assuming statistical distributions of Fe3+ ligand coordinates has revealed the existence of a certain degree of local disorder in FexGa1−xBO3 single crystals.

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55-59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fibres expressing the type I but not the IIa myosin heavy chain (MyHC) isoform. In comparison to non-users, higher specific force was recorded in HRT users both in muscle fibres expressing type I (∼27%; P < 0.05) and type IIa (∼23%; P < 0.05) MyHC isoforms. These differences were fibre-type dependent, i.e. the higher specific force in fast-twitch muscle fibres was primarily caused by higher force per cross-bridge while slow-twitch fibres relied on both a higher number and force per cross-bridge. HRT use had no effect on fibre cross-sectional area (CSA), velocity of unloaded shortening (V0) and relative proportion of MyHC isoforms. In conclusion, HRT appears to have significant positive effects on both regulation of muscle contraction and myonuclei organization in postmenopausal women.

This review is devoted to the critical analysis of advantages and disadvantages of existing mixture descriptors and their usage in various QSAR/QSPR tasks. We describe good practices for the QSAR modeling of mixtures, data sources for mixtures, a discussion of various mixture descriptors and their application, recommendations about proper external validation specific for mixture QSAR modeling, and future perspectives of this field. The biggest problem in QSAR of mixtures is the lack of reliable data about the mixtures' properties. Various mixture descriptors are used for the modeling of different endpoints. However, these descriptors have certain disadvantages, such as applicability only to 1 : 1 binary mixtures, and additive nature. The field of QSAR of mixtures is still under development, and existing efforts could be considered as a foundation for future approaches and studies. The usage of non-additive mixture descriptors, which are sensitive to interaction effects, in combination with best practices of QSAR model development (e.g., thorough data collection and curation, rigorous external validation, etc.) will significantly improve the quality of QSAR studies of mixtures.

studied the effect ofpressure of argon as working gas at a constant distance of5cm between PTFE target and a substrate. It was shownthat both the chemistry, and the roughness of the surfacechanged with the Ar pressure during sputtering. Theauthorsconsideredthesurfaceroughnesstobeimportantfor the targeted super-hydrophobic effect. However, theroughness did not increase gradually with the pressure,but increased by a sudden jump for the highest pressure70Pa used. This result was interpreted as indicatingthat the plasma polymer clusters (nano and microparticles)formedintheplasmavolumewereburiedinto the plasma polymer film growing on the substrate.This happened under particular deposition conditions(flow of argon, RF power, target-substrate distance) atAr pressure of about 70Pa and higher. Based onscanningelectron microscopy (SEM) micrographs, this seemed toconfirmthehypothesisthatfluorocarbonplasmapolymerparticlesoriginatingintheplasmavolume(dustyplasma)were eventually embedded into the film growing onthe substrate.On the other hand, several research groups claimed thatclusters (actually PTFE crystals) grown from CF

Hyla arborea schelkownikowi is one of the leaf frog species inhabiting the southern territories of Russia and the former USSR. This frog species is a member of the Hylidae Rafinesque, 1815 batrachians family. The present study deals with the previously uninvestigated peptidome of the Hyla arborea schelkownikowi skin secretion. Nano-electrospray ionization Fourier transform mass spectrometry (nanoESI-FTMS) of the skin secretion, in the intact form and after acetylation, was selected as the general method of analysis. Electron-capture dissociation (ECD) and collision-induced dissociation (CID) fragmentation were both employed, while de novo sequencing was performed by manual interpretation of the MS data. The suppression of the cyclization of b-ions in the mass spectrometer by the acetylation reaction proved to be very efficient for the de novo sequencing of short peptides. Ten skin peptides were found and all of them, except for bradykinin, had not previously been reported. Six of the peptides belong to the tryptophyllins and related peptides, while three peptides are similar to the aureins.

In this article the calculation scheme of new molecular descriptors on the basis of symbiosis of the informational field model and simplex representation of molecular structure (so-called, simplex-informational descriptors) is introduced. The following advantages of the proposed descriptors are demonstrated: i) high-sensitivity to molecular structure changes; ii) good mechanistic interpretation; and iii) the ability to produce well-fitted, robust and predictive QSAR models. The efficiency of the method is also demonstrated on the example of QSAR analysis of angiotensin converting enzyme (ACE) inhibitors, acetylcholinesterase (AChE) inhibitors, and ligands of 5-HT1A receptors. QSAR tasks have been solved using the PLS-method. Resulting 2D models are obtained using simplex-informational and original simplex descriptors and were also compared with descriptors generated by other QSAR approaches (COMFA, COMSIA, EVA, HQSAR). The advantage of the developed method over others are shown by the comparison of different statistical characteristics.

In this article the Hierarchical QSAR technology (HiT QSAR) has been used for consensus QSAR modeling of Acetylcholinesterase (AChE) inhibition by various organophosphate compounds. Simplex representation of molecular structure (SiRMS) and Lattice model (LM) QSAR approaches have been used for descriptors' generation. Statistical models have been obtained by partial least squares (PLS) method. Various chiral organophosphates represented by their (R)- and (S)-isomers, racemic mixtures and achiral structures have been investigated. Successful consensus model (R2=0.978) based on fourteen best QSAR models obtained using different QSAR approaches and training sets for several levels and methods of molecular structure representation (2.5D, double 2.5D, and 3D) has been used for the prediction of AChE inhibition of new compounds. In order to avoid chance correlations 1000 rounds of Y-scrambling were performed for each selected model. Leverage and ellipsoid Applicability domain (DA) approaches have been used for additional estimation of the quality of prognosis. Molecular fragments enhancing and interfering with inhibitory activity have been determined. It was revealed that atom's individuality and stereochemistry of chiral surroundings of the asymmetric atom of phosphorus play a vital role in AChE inhibition. Thus, (R)-isomers are always less active than the (S) isomers and the racemate. HiT QSAR proves to be a powerful tool for investigation of activity of stereo selective interactions and can be used in such subsequent studies.

The influence of molecular structure of 4-thiazolidone derivatives (about 70 compounds) on their antimicrobial activity has been investigated by QSAR approach based on Simplex Representation of Molecular Structure (SiRMS). This method is characterized by the absence of molecular alignment problem as well as by taking into account the different atom characteristics (partial charge, lipophilicity, etc) and the possibility of drug design. The following micro-organisms were used as reference cultures: Candida albicans S, Citrobacter freundii, Klebsiella pneumoniae, Pseudomonas aeruginosa (R and S strains) and Staphylococcus aureus MSSA. Statistical characteristics of QSAR models obtained by Partial Least Squares (PLS) method are rather good (R2=0.843–0.989, Q2=0.679–0.864, R2test=0.744–0.943). Y-scrambling test shows the possibility of chance correlations for equations developed for C. freundii and K. pneumonia. These two cultures were excluded from subsequent analysis. The molecular fragments promoting/interfering with antimicrobial activity and degree of their influence on the activities have been determined. Thus, naphthalene-substituted fragment (irrespective to its location within the molecule) decreases the antimicrobial activities significantly. The requirements to molecular design were formulated; e.g. highly active compounds must contain indole fragment. In addition, the influence of heterocyclic system evolution on antimicrobial properties of 4-thiazolidones derivatives was demonstrated. The important role of electrostatic characteristics of their molecular structure was also shown. The compounds with the highest predicted values of antimicrobial activities against several cultures were chosen as a result of virtual screening.

Amphibian skin glands are known to secrete various types of bioactive peptides. The array of these peptides is specific for every frog species. The present research deals with the identification of peptides isolated from the skin secretion of the Marsh frog R. ridibunda inhabiting the Kolkhida Canyon of the Caucasian region. The research is based on comprehensive high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) analysis of intact and chemically modified peptides. In particular, an oxidation procedure was applied directly to the crude skin secretion to open SS loops whereas N-terminal acetylation was additionally carried out for one individual peptide. Sequences were determined by manual interpretation of electron capture dissociation (ECD) and collisionally induced dissociation (CID) tandem mass spectra. A total of 29 peptides were identified in the skin secretion of the Caucasian Marsh frog. The peptide profile is represented with disulfide-containing peptides belonging to the brevinin, esculentin and ranatuerin families, neuropeptides of the bradykinin and bombesin families. Two identified peptides belonging to the ranatuerins are the first peptides of this family discovered in the skin secretions of European frogs. Ten of the identified peptides coincide with those reported earlier for the European Edible frog. Another ten are identical to those found in R. ridubunda from the Moscow region. This fact verifies the described method as being an efficient analytical tool to compare intra- and interspecific variabilities. Copyright © 2008 John Wiley & Sons, Ltd.

The role of the inositol lipid 5-phosphatase (SHIP2) in preadipocyte signaling is not known. Although overexpression of SHIP2 inhibited proliferation and 3H-thymidine incorporation in 3T3-L1 preadipocytes, there was no effect on insulin-induced adipogenesis. Insulin promoted SHIP2 tyrosine phosphorylation in differentiated 3T3-L1 adipocytes, but did not do so in preadipocytes. The absence of SHIP2 tyrosine phosphorylation suggests a potential explanation for the isolated rise in PI(3,4,5)P3, without any changes in PI(3,4)P2, previously observed following insulin treatment of these cells. Lack of SHIP2 tyrosine phosphorylation by insulin was also observed in primary cultures of human abdominal subcutaneous preadipocytes. These cells also produced PI(3,4,5)P3, but not PI(3,4)P2, in response to insulin. Comparison of insulin vs. PDGF treatment on SHIP2 tyrosine phosphorylation in 3T3-L1 and human preadipocytes revealed that only PDGF, which stimulates the accumulation of PI(3,4,5)P3 as well as PI(3,4)P2, was active in this regard, and only PDGF promoted the association of 52 kDa form of Shc with SHIP2. Nevertheless, both insulin and PDGF were equally effective in translocating SHIP2 to the plasma membrane in 3T3-L1 preadipocytes. Lack of SHIP2 tyrosine phosphorylation may account for the insulin-specific inositol phospholipid pattern of accumulation in preadipocytes. J. Cell. Physiol. 197: 243–250, 2003© 2003 Wiley-Liss, Inc.