Correlated conformational dynamics of the human GluN1-GluN2A type N-methyl-D-aspartate (NMDA) receptor.

N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels found in the nerve cell membranes. As a result of overexcitation of NMDARs, neuronal death occurs and may lead to diseases such as epilepsy, stroke, Alzheimer's disease, and Parkinson's disease. In this study, human GluN1- GluN2A type NMDAR structure is modeled based on the X-ray structure of the Xenopus laevis template and missing loops are added by ab-initio loop modeling. The final structure is chosen according to two different model assessment scores. To be able to observe the structural changes upon ligand binding, glycine and glutamate molecules are docked into the corresponding binding sites of the receptor. Subsequently, molecular dynamics simulations of 1.3 µs are performed for both apo and ligand-bound structures. Structural parameters, which have been considered to show functionally important changes in previous NMDAR studies, are monitored as conformational rulers to understand the dynamics of the conformational changes. Moreover, principal component analysis (PCA) is performed for the equilibrated part of the simulations. From these analyses, the differences in between apo and ligand-bound simulations can be summarized as the following: The girdle right at the beginning of the pore loop, which connects M2 and M3 helices of the ion channel, partially opens. Ligands act like an adhesive for the ligand-binding domain (LBD) by keeping the bi-lobed structure together and consequently this is reflected to the overall dynamics of the protein as an increased correlation of the LBD with especially the amino-terminal domain (ATD) of the protein.

A novel measure to analyze protein structures: Aspect ratio in protein alpha shapes.

Proteins' three-dimensional (3D) structures are analyzed traditionally using geometric descriptors such as torsional angles and inter-atomic distances. In this study a measure that is borrowed from computational geometry, aspect ratio of each tetrahedron in alpha shapes of proteins, is utilized. This geometric descriptor differentiates alpha and beta structural classes of proteins when combined with principal components analysis. The method converts the structures of individual proteins, 3D coordinates of the atoms, to points on a plane. It has a high degree of accuracy in differentiating R and T structures of hemoglobin. Therefore, it is anticipated that the geometric measure can be used successfully in a method that is extended to solve classification problems in machine learning.

The role of FAS gene variants in inflammatory bowel disease.

BACKGROUND/AIMS: The analysis of genes thought to be important in inflammatory bowel disease (IBD) has shown that more than half of IBD-related genes are also associated with other autoimmune diseases. The aim of this study was to detect a possible association between the polymorphisms of the (-670 A/G, -1377 G/A) fFas cell surface death receptor (FAS) gene promoter and susceptibility to IBD in the Turkish population. MATERIALS AND METHODS: In total, 125 patients with IBD, including 73 ulcerative colitis and 52 Crohn's disease and also 101 healthy controls without any pathological signs of IBD were considered for the study. Real-time polymerase chain reaction technique was used to detect FAS polymorphisms in this study. RESULTS: The analysis of FAS -670 A/G polymorphism indicated that the frequency of GG genotype was significantly increased in patients compared with controls (p<0.001). Additionally, AG genotype (p<0.001) and A allele (p<0.001) frequencies were higher in controls than in patients. The analysis of FAS -1377 G/A polymorphism revealed that the frequency of AA genotype was meaningfully increased in patients compared with controls (p<0.001). Additionally, GG genotype (p<0.001) and G allele (p<0.001) frequencies were increased in controls when compared with patients. CONCLUSION: FAS -670A/G GG genotype seemed to be a protective allele against IBD; however, AA genotype and A allele were associated with elevated risk of IBD. In the FAS -1377G/A polymorphism, frequencies of the G allele and GG genotype were observed to be protective against IBD, whereas AA, GA genotypes, and A allele frequency increased in the patient group.

The relationship between perceived interpersonal competence and self-disclosure in an online context: The moderating role of shyness.

The purpose of this study is to examine the reported level of self-disclosure in online communication and understand the relationship between perceived interpersonal competence and self-disclosure in an online context, taking into account the moderating role of shyness. The study sample consists of university students (N = 585). Hierarchical multiple linear regression analyses revealed that, controlling for participants' online media use, shyness moderated the relationship between online self-disclosure and perceived interpersonal competence. Moderation results showed that the relationship between online self-disclosure and perceived interpersonal competence was weaker for individuals with higher levels of shyness, and stronger for those with moderate or low scores on the shyness measure. The study's implications and contributions to the existing literature are discussed.

Self-Handicapping Among University Students: The Role of Procrastination, Test Anxiety, Self-Esteem, and Self-Compassion.

The purpose of the present study was to examine the predictor role of procrastination, test anxiety, self-esteem, and self-compassion for the variation in university students' self-handicapping. The sample of the study consisted of 801 undergraduate students (404 females and 397 males). In order to collect data, Self-Handicapping Scale, Tuckman Procrastination Scale, Anxiety Subscale of Academic Emotions Questionnaire, Rosenberg Self-Esteem Scale, and Self-Compassion Scale were used. Stepwise regression analysis was conducted, and results showed that all of the predictor variables significantly contributed in explaining self-handicapping. The model explained the 59% of the variance in self-handicapping, whereas semi-partial variance of procrastination, test anxiety, self-esteem, and self-compassion were 17%, 4%, 2%, and 2%, respectively.

Heterofunctional Magnetic Metal-Chelate-Epoxy Supports for the Purification and Covalent Immobilization of Benzoylformate Decarboxylase From Pseudomonas Putida and Its Carboligation Reactivity.

In this study, the combined use of the selectivity of metal chelate affinity chromatography with the capacity of epoxy supports to immobilize poly-His-tagged recombinant benzoylformate decarboxylase from Pseudomonas putida (BFD, E.C. 4.1.1.7) via covalent attachment is shown. This was achieved by designing tailor-made magnetic chelate-epoxy supports. In order to selectively adsorb and then covalently immobilize the poly-His-tagged BFD, the epoxy groups (300 µmol epoxy groups/g support) and a very small density of Co(2+)-chelate groups (38 µmol Co(2+)/g support) was introduced onto magnetic supports. That is, it was possible to accomplish, in a simple manner, the purification and covalent immobilization of a histidine-tagged recombinant BFD. The magnetically responsive biocatalyst was tested to catalyze the carboligation reactions. The benzoin condensation reactions were performed with this simple and convenient heterogeneous biocatalyst and were comparable to that of a free-enzyme-catalyzed reaction. The enantiomeric excess (ee) of (R)-benzoin was obtained at 99 ± 2% for the free enzyme and 96 ± 3% for the immobilized enzyme. To test the stability of the covalently immobilized enzyme, the immobilized enzyme was reused in five reaction cycles for the formation of chiral 2-hydroxypropiophenone (2-HPP) from benzaldehyde and acetaldehyde, and it retained 96% of its original activity after five reaction cycles.

Children's sense of loneliness and social dissatisfaction, after-school care.

The study examined the loneliness and social dissatisfaction of elementary school students in relation to type of after-school care. 358 students completed the Loneliness and Social Dissatisfaction Scale and an information form that included age and the students' after-school care arrangements. Results indicated that children who were in self or sibling care had greater loneliness and social dissatisfaction compared to their peers under formal center care.

Carboligation reactions mediated by benzoylformate decarboxylase immobilized on a magnetic solid support.

In this study, magnetic nanoparticles (Fe3 O4 , magnetite) with immobilized metal affinity ligands (MSS) were prepared and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), and vibrating-sample magnetometer (VSM) methods for purification and immobilization of the histidine-tagged recombinant benzoylformate decarboxylase (BFD). The MSS support was shown to be eligible for selective binding of HIS-tagged BFD by SDS-page analysis. Loading capacity of the MSS support was determined as 43.6 ± 1.1 mg/g. The regeneration ability for protein binding was also studied. An immobilized BFD was tested to catalyze benzoin condensation and representative cross acyloin reaction. Conversion and enantiomeric excess values were comparable with that of free enzyme catalyzed reactions.

Assessment of reliability and validity of the Turkish version of Heartland Forgiveness Scale.

The current study investigated the reliability and validity of the Turkish version of the Heartland Forgiveness Scale (HFS). The Turkish version of the HFS, the Ruminative Response Scale (RRS), and the Satisfaction with Life Scale (SWLS) were administered to 796 Turkish university students (430 women, 366 men) with a mean age of 20.6 yr. (SD = 2.1). Internal consistency reliability was calculated and Cronbach alpha coefficients ranged between .71 and .82. Criterion validity (Pearson correlation) between the HFS and other scales ranged from -.09 to .34. Additionally, a confirmatory factor analysis was conducted to assess the fit of the standard three-factor solution of the HFS. The results suggested that the Turkish version of the HFS had adequate internal consistency, criterion validity, and reflected the standard three-factor structure, indicating that it can be reliably used to measure forgiveness among a Turkish sample.

Psychometric properties of Frustration Discomfort Scale in a Turkish sample.

The present study assessed the psychometric properties of the Frustration Discomfort Scale for Turkish college students. The Frustration Discomfort Scale (FDS), Procrastination Assessment Scale-Student, and Rosenberg Self-Esteem Scale were administered to a sample of 171 (98 women, 73 men) Turkish college students. The results of the confirmatory factor analysis yielded fit index values demonstrating viability of the four-dimensional solution as in the original. Findings also revealed that, as predicted, the Discomfort Intolerance subscale of Turkish FDS was most strongly correlated with procrastination. Overall results provided evidence for the factor validity and reliability of the Turkish version of the scale for use in a Turkish population.

Factors affecting the electrochemical regeneration of NADH by (2,2'-bipyridyl) (pentamethylcyclopentadienyl)-rhodium complexes: impact on their immobilization onto electrode surfaces.

Complexes of the (2,2'-bipyridyl) (pentamethylcyclopentadienyl)-rhodium family ([Cp*Rh(bpy)Cl](+), which is actually hydrolyzed in the form of [Cp*Rh(bpy)H(2)O](2+) in aqueous medium) are suitable solution-phase mediators likely to regenerate nicotinamide cofactors associated to dehydrogenases involved in many biocatalytic applications. Their practical application as bioelectrocatalysts, e.g., in fine chemicals synthesis or biosensors, remains however restricted to their durable immobilization in an active form onto solid electrode surfaces. This paper reports some new observations on the electrocatalytic properties of this mediator towards NAD(+) reduction, notably the critical effect of pH and cofactor-to-mediator concentration ratio, and investigates the behavior of a series of ([Cp*Rh(bpy)Cl](+)) derivatives bearing various substituents on the bipyridine ligand in view of their subsequent integration in electrochemical bioreactors. It will be shown that such compounds containing S- or N- moieties (i.e., often used as precursors to functionalize electrode surfaces) lead to inactivation of the electrocatalyst because their interaction with the Rh center prevents the formation of the active rhodium hydride complex. It was thus necessary to find another strategy of immobilization, and we found that adsorption of [Cp*Rh(bpy)Cl](+) by π-stacking on single-walled carbon nanotubes is an effective mean to reach this goal, leading to efficient and stable catalytic responses for NAD(+) reduction. Preliminary electroenzymatic experiments in the presence of d-sorbitol dehydrogenase further point out the interest of this approach for bioelectrocatalysis purposes and provide the proof-of-concept for this immobilization strategy.

Selective oxidation and reduction reactions with cofactor regeneration mediated by galactitol-, lactate-, and formate dehydrogenases immobilized on magnetic nanoparticles.

Rapid immobilization with the one-pot purification of galactitol dehydrogenase (GatDH) and formate dehydrogenase (FDH) is achieved by using iminodiacetic acid (IDA) with chelated Co(2+) modified magnetic nanoparticles as a carrier. Lactate dehydrogenase (LDH) from recombinant Escherichia coli and FDH commencing Candida methylica were used as an auxiliary enzyme for the regeneration of NADH/NAD(+) with a representative synthesis of (S)-1,2-propanediol and l-tagatose starting from hydroxyacetone and galactitol. The affinity magnetic nanoparticles were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), while the purity of GatDH and FDH was assayed by SDS-PAGE analysis. The immobilized two-enzyme system, reflecting the pH dependence of its constituent enzymes, showed optimal activity at pH 7 and 8 for (S)-1,2-propanediol and l-tagatose production, respectively. The immobilized enzyme system retained up to 70% of its activity after one week of repeated use. The use of affinity magnetic nanoparticles offers the advantage of a one-pot purification of His(6)-tagged GatDH and FDH followed by the production of rare sugar and chiral diol.

Benzaldehyde lyase catalyzed enantioselective self and cross condensation reactions of acetaldehyde derivatives.

Flexible protected 1,3,4-trihydroxy-2-butanone is synthesized in high enantiomeric excesses by using asymmetric homo- and cross- acyloin coupling of aliphatic aldehydes catalyzed by benzaldehyde lyase.

Enantioselective production of benzoin from benzoin acetate via kinetic resolution and deracemization using Rhizopus oryzae.

In this study, the production of enantiopure benzoin from rac-benzoin acetate was achieved by lipase catalyzed kinetic resolution combined with deracemization using Rhizopus oryzae (CBS111718). The growth cells were pretreated with 20 kHz and 30 kHz ultrasound irradiation and mechanical homogenization. Approximately 100% conversion and 96% enantiomeric excess of the product (S-benzoin) were obtained by applying 20 kHz ultrasound irradiation at pH 6. The deracemization process involves new and important processes that allow for the transformation of a racemate into a single stereoisomeric product in 100% theoretical yields. Moreover, the application of ultrasound increases the conversion rate by reducing mass transfer limitation.

Carboxylic acid derivatives of histone deacetylase inhibitors induce full length SMN2 transcripts: a promising target for spinal muscular atrophy therapeutics.

INTRODUCTION: Proximal spinal muscular atrophy (SMA) is a common autosomal recessively inherited neuromuscular disorder. It is caused by homozygous absence of the survival motor neuron 1 (SMN1) gene. SMN2, which modulates the severity of the disease, represents a major target for therapy. The aim of this study was to investigate whether SMN2 expression can be increased by caffeic acid, chlorogenic acid and curcumin, which are designed by modifications of the carboxylic acid class of histone deacetylase (HDAC) inhibitors. MATERIAL AND METHODS: Using quantitative real-time PCR, we analysed the levels of full-length SMN2 and Δ7SMN2 mRNA. We performed LDH cytotoxicity assay to analyse whether SMN2 activating concentrations of caffeic acid, chlorogenic acid and curcumin were cytotoxic to fibroblasts. RESULTS: We found that caffeic acid and curcumin were more efficient than chlorogenic acid and increased full-length SMN2 mRNA levels 1.5 and 1.7-fold, respectively. Δ7SMN2 mRNA levels were measured to investigate alternative splicing of exon 7. We also found that cytotoxicity was not observed at SMN2 activating concentrations. CONCLUSIONS: Our data suggest that carboxylic acid derivatives including phenolic structure and symmetry could be a good candidate for SMA treatment.

Gold(I)/Zn(II) catalyzed tandem hydroamination/annulation reaction of 4-yne-nitriles.

The tandem hydroamination-annulation reaction of 4-pentyne-nitriles in the presence of amine nucleophiles and a cooperatively operating catalyst system, consisting of Ph(3)PAuCl and Zn(ClO(4))(2), provides an efficient route to 2-aminopyrroles. Two regioisomeric 2-aminopyrroles were formed in moderate to good yields.

Chemoenzymatic conversion of linoleic acid into conjugated linoleic acid.

An efficient chemoenzymatic method for preparing conjugated linoleic acid (CLA) using free linoleic acid (LA) as a substrate is described. In the first step, LA was transformed into 10-hydroxy-cis-12-octadecenoic acid (HA) by the whole cells of Lactobacillus plantarum after 48 h of incubation. The preincubation of whole cells with 0.03% LA resulted in a better yield of HA (480 mg/g) compared to cells grown without LA. In a second fast microwave step, HA was converted to cis-9,trans-11-octadecadienoic acid in the presence of iodine as a catalyst over a silica gel surface. The advantage of this method in preparing cis-9,trans-11 CLA is simple via the whole cell bioconversion of LA into HA via L. plantarum followed by the fast microwave-assisted synthesis of cis-9,trans-11 CLA in higher yields.

Understanding the mode of action of ThDP in benzoylformate decarboxylase.

The mechanism of all elementary steps involved in the catalytic cycle of benzoylformate decarboxylase (BFD, E.C. 4.1.1.7) to generate the acyloin linkage is investigated by extensive molecular dynamics simulations. Models involving different charge states of amino acids and/or mutants of critical residues were constructed to understand the involvement of the catalytically active residues and the reactivity differences between different substrates in this reaction. Our calculations confirm that H70, S26, and H281 are catalytically active amino acids. H281 functions as a base to accept H(donor) in the first nucleophilic attack and as an acid in the second, to donate the proton back to O(acceptor). S26 assists H281 in deprotonation of the donor aldehyde and protonation of the acceptor aldehyde. In both the first and second nucleophilic attacks, H70 interacts with O(aldehyde) and aligns it toward the nucleophilic center. H70 has been found to have an electrostatic effect on the approaching aldehyde whose absence would block the initiation of the reaction. The reactivity difference between benzaldehyde (BA) and acetaldehyde (AA) is mainly explained by the steric interactions of the acceptor aldehyde with the surrounding amino acids in the active center of the enzyme.

Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies.

In the light of known HDAC inhibitors, 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure-activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses of inhibitor-enzyme complexes. Of these compounds, caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate, which is a well-known HDAC inhibitor.

Chronic procrastination among Turkish adults: exploring decisional, avoidant, and arousal styles.

The authors examined the prevalence of chronic procrastination (decisional, avoidant, and arousal styles) as functions of demographic variables among 354 Turkish adults (148 men, 206 women; M age = 38.7 years, SD = 8.26 years). Prevalence analyses showed that among Turkish participants, 17.5% were indecisive procrastinators, 13.8% were avoidant procrastinators, and 14.7% were arousal procrastinators. Results did not yield significant differences for gender or age on any forms of procrastination, which is consistent with other international samples. However, significant differences emerged depending on the number of children such that Turkish adults who had more than 3 children claimed to be more indecisive than they claimed to be arousal or avoidant procrastinators. Respondents with less than a graduate degree reported higher rates of indecision than did respondents with at least a graduate degree.