Adaptation of the Morningness–Eveningness Stability Scale improved (MESSi) into Turkish

Morningness–eveningness is an individual difference that is related with various traits such as behavioral problems, personality, and health. The aim of the current study is to adopt the Morningness–Eveningness Stability Scale improved (MESSi) which is a novel assessment tool that consists of subscales of morning affect (MA), eveningness (EV), and distinctness (DI) into Turkish. Concurrent validity of the MESSi along with Big five inventory (BIG-5), Subjective alertness level, Pittsburg Sleep Quality Index (PSQI), Positive and Negative Affect Schedule (PANAS) were analyzed. The scale was administered to 1,076 high school and university students aged 14–47 years (M = 19.49, SD = 3.53). The explanatory factor analysis (EFA) and confirmatory factor analysis (CFA) revealed the three-factor structure of MESSi. According to the concurrent validity result of the MESSi with BIG-5, conscientiousness was found to correlate positively with MA and negatively with EV. Also, extraversion showed a negative correlation with DI and positive correlation with MA. Furthermore, the subjective alertness rating results showed that MA was positively related to alertness in the morning hours and negatively in the evening hours. Also, sleep quality-related results showed that EV and DI are positively related to total PSQI scores and negatively related to MA. In addition, concerning positive affect (PA) and negative affect (NA), MA was positively related with PA and negatively with NA, while DI was negatively related with PA and positively with NA. In overall, MESSi is a valid and reliable instrument and can be used in Turkish students.     

Morningness–eveningness and amplitude – development and validation of an improved composite scale to measure circadian preference and stability (MESSi)

Measuring morningness–eveningness is an important aspect of individual differences because it is associated with many aspects of personality and health. The present study outlines recent advancements in the field of measurement and proposes an improved assessment of morningness–eveningness, such as the measurement of circadian amplitude, updating and reflecting new item developments, addressing the clock time based measures, the morning-biased items and the aspect of uni versus multidimensionality. Four studies have been carried out in Germany to present a novel development (with a total sample of N = 1181). In study I, the exploratory factor analysis (EFA) revealed three dimensions, one of morningness, one of eveningness and one of amplitude/stability. Then, items were reduced to present a clearer factor structure by removing ambiguous items. In the second study, a shortened questionnaire was applied, with 15 items (5 per construct), but Confirmatory Factor Analysis (CFA) did not provide acceptable fit indices. Refining items were made in study III, which again showed a clearer factor structure in EFA, and subsequently, in study IV, the refined set of 15 items provided a good fit of a CFA. The final questionnaire was tested for validity by applying clock times, personality questions and alertness ratings. Thus, this newly developed questionnaire contains three distinct dimensions. To reflect the new content, the scale is labelled morningness–eveningness-stability-scale improved (MESSi).     

Validity of the Morningness‐Eveningness Scale for Children among Spanish Adolescents

Adolescents tend to be much later chronotypes than other age groups. This circadian phase delay is attributed as much to biological as psychosocial factors. Because the consequences of this change on performance and health have been documented, questionnaires to identify morning and evening‐type adolescents are necessary. The aim of the present study was to validate a Spanish version of the Morningness‐Eveningness Scale for Children (MESC) by means of several relevant psychological variables as external criteria. A sample of 623 urban high school students completed the MESC and self‐reported measures of sleep behaviors, subjective alertness, physical performance, and mood. On the whole, results indicate a good validity of MESC. Significant differences in the self‐reported ratings between morning and evening types were obtained by time‐of‐day. These results provide preliminary support for the Spanish version of MESC.     

Reliability and validity of the Korean version of Morningness–Eveningness Questionnaire in adults aged 20–39 years

Morningness–Eveningness (ME) can be defined by the difference in individual diurnal preference observed from general behavioral patterns including sleep habits. The Horne & Östberg Morningness–Eveningness Questionnaire (MEQ) has been used for classifying ME types. We examined the reliability of a Korean version of the MEQ (Korean MEQ) and verified its validity by comparing responses on the Korean MEQ to objectively-recorded sleep–wake rhythms. After translating and back translating the MEQ from English into Korean, we examined the internal consistency of 19 items of the Korean MEQ in 91 subjects, and the test–retest reliability in 21 subjects who took the Korean MEQ twice, 4 weeks apart. The Korean MEQ was then administered to 1022 young adult subjects. A subset of 46 morning, neither, and evening type subjects took part in a validation study in which their rest-activity timing was collected by actigraphy for 7 days. Cosinor analyses on these data were done to obtain the acrophase and amplitude of the sleep–wake rhythm. Cronbach’s alpha of the total scores from the Korean MEQ was 0.77, and the test–retest reliability intra-class correlation coefficient was 0.90 (p?<?0.0001). There was a significant negative correlation between Korean MEQ score and reported sleep–wake timing among the entire cohort (p?<?0.0001). There was a significant difference in bedtime and wake time (on both work and free days), and in the mean sleep–wake rhythm acrophase, between ME types (p?<?0.01). In this study, the validity of the Korean MEQ was verified by illustrating the difference in acrophases of the sleep–wake rhythm between the ME types in young adults.     

Morningness–eveningness interferes with perceived health,physical activity,diet and stress levels in working women: A cross-sectional study

Sleep and health are closely interrelated and sleep quality is a well-known contributor to perceived health. However, effects of sleep-timing preference i.e. morningness–eveningness on health has yet to be revealed. In this study, we explored the relationship between morningness–eveningness and perceived health in a sample of female working professionals (N?=?202). Sleep-timing preference was measured using the Composite Scale of Morningness. Perceived health was characterized by Center for Epidemiologic Studies Depression Scale, WHO Well-Being Scale-5 and Patient Health Questionnaire-15 scores. We also investigated possible mechanisms, including stress and health-impairing behaviours. In accordance with previous data, we found more depressive mood, lower well-being and poorer perceived health among evening types. To assess health-impairing behaviours we collected data on smoking habits, alcohol consumption, physical activity and diet. Among the possible mechanism variables, greater stress, less frequent physical activity and less healthy diet were associated with eveningness. Furthermore, stress diminished the strength of the association between morningness–eveningness and depressed mood. Physical activity attenuated the strength of the association between morningness–eveningness and well-being. No effects of alcohol consumption could be identified. Our data show that evening preference behaves as a health risk in terms of associating with poor perceived health. Our findings also suggest that this effect might be mediated by health behaviours and stress.     

Combination of bioimprinting and silane precursor alkyls improved the activity of sol–gel-encapsulated lipase

Bioimprinting and sol–gel encapsulation of lipases by silane precursors are efficient methods of enhancing lipase performance in non-aqueous medium. The correlation between bioimprinting, the alkyl-chain length of silane precursors, and the catalytic activity of gel-encapsulated lipase was investigated using a series of silane precursors: methyltrimethoxysilane (MTMS), vinyltrimethoxysilane (VTMOS), vinyltriethoxysilane (VTEOS), and n-octyltrimethoxysilane (OTMOS). The optimal parameters for lipase immobilization were also determined. Both bioimprinting and increasing the chain-length of alkyl groups, apparently by increasing hydrophobicity, significantly improved the specific activity and the total activity of the immobilized lipase. Compared to a non-imprinted MTMS/TMOS gel, the specific activity of an imprinted OTMOS/TMOS gel improved 14.4-fold, and the total activity improved 6.8-fold. Nitrogen adsorption–desorption assays and gel matrix surface characterization showed that the bioimprinting molecule and the hydrophobic alkyl groups of silane triggered lipase to change from the closed to the open conformation, and contributed to creating sol–gel matrices that were more porous and with less mass transfer resistance structure, apparently improving the activity of encapsulated lipase.     

Structure–activity relationship of celecoxib and rofecoxib for the membrane permeabilizing activity

Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory effect by inhibiting cyclooxygenase activity. We previously suggested that in addition to cyclooxygenase-inhibition at the gastric mucosa, NSAID-induced gastric mucosal cell death is required for the formation of NSAID-induced gastric lesions in vivo. We showed that celecoxib exhibited the most potent membrane permeabilizing activity among the NSAIDs tested. In contrast, we have found that the NSAID rofecoxib has very weak membrane permeabilizing activity. To understand the membrane permeabilizing activity of coxibs in terms of their structure–activity relationship, we separated the structures of celecoxib and rofecoxib into three parts, synthesized hybrid compounds by substitution of each of the parts, and examined the membrane permeabilizing activities of these hybrids. The results suggest that the sulfonamidophenyl subgroup of celecoxib or the methanesulfonylphenyl subgroup of rofecoxib is important for their potent or weak membrane permeabilizing activity, respectively. These findings provide important information for design and synthesis of new coxibs with lower membrane permeabilizing activity.     

Changes in the protein and activity levels of the plastid NADH–plastoquinone–oxidoreductase complex during fruit development

Plastids contain an NADH dehydrogenase complex (Ndh complex) homologous to the mitochondrial complex I (EC 1.6.5.3). In this work, we have analysed the changes in the Ndh complex during ripening of pepper (Capsicum annum L., cv. Maor) and tomato (Lycopersicon esculentum Mill., cv. Marglobe) fruits. The Ndh complex was mainly present in the outer pericarp of tomato fruits, whereas it was evenly distributed in the pericarp of pepper. In both kinds of fruit we observed a decrease in the total amount of Ndh complex from the green to the red stage of development. This decrease corresponds to parallel decreases in the content and activity of the complex in plastids during the transition from chloroplasts to chromoplasts. Levels of plastidial quinol peroxidase activity were also higher during the first stages of tomato fruit development than during the latter stages of ripening. However, when referred to total plastid protein, the amount and activity of the Ndh complex in chloroplasts isolated from green fruits was higher than in chloroplasts isolated from leaves. These results strongly suggest that function of the Ndh complex, probably related to a plastidial electron transport chain, can be important during the first stages of fruit development.     

Structure–activity relationship (SAR) of parthenin analogues with pro-apoptotic activity: Development of novel anti-cancer leads

Analogues of parthenin were synthesized by substitutions at different reaction centres to establish a structure–activity relationship (SAR). Some of the molecules have displayed significant cytotoxicity in human cervical carcinoma (HeLa) and human myeloid leukemia (HL-60) cells. A few of the compounds also induced apoptosis in HL-60 cells measured in terms of sub-Go/G1 DNA fraction. Also one of the lead molecules has been shown to be the inhibitor of both telomerase and topoisomerase-II.     

Why are programmes for offenders with personality disorder not informed by the relevant scientific findings?

This paper examines the evidence to justify intervening in those with personality disorder, specifically antisocial personality disorder (ASPD) as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, American Psychiatric Association 1994). The evidence from randomized controlled trials in the mental health literature is reviewed and found to be deficient with only five trials satisfying Cochrane criteria, all of which had a reduction in substance misuse as their primary outcome, rather than a change in the personality disorder per se.Next, I consider the contribution of Thomas Kuhn to explain why it is difficult to develop a scientific basis in forensic mental health. I argue that, because forensic mental health is inclusive in its purpose (interacting with the law, social services and the penal system, all of which have different rules and agendas), it is difficult to develop a consensus on fundamentals, this consensus being a hallmark of a science.Finally, I argue that despite the absence of evidence from mental health, providers for ASPD are in a fortunate position in being able to draw upon the correctional literature. This is relevant, provided that we agree that a reduction in offending is the primary outcome. While mental health can learn much from correctional practice, it can also enhance the efficacy of the latter by, for instance, drawing attention to the specific vulnerabilities of the personality structure that might impede programme delivery in correctional settings. Means of achieving a conjunction of mental health and correctional practice are urgently required as this would be beneficial to both.     

Tacrine–propargylamine derivatives with improved acetylcholinesterase inhibitory activity and lower hepatotoxicity as a potential lead compound for the treatment of Alzheimer’s disease

Abstract

A series of tacrine–propargylamine derivatives were synthesised and evaluated as possible anti-Alzheimer’s disease (AD) agents. Among these derivatives, compounds 3a and 3b exhibited superior activities and a favourable balance of AChE and BuChE activities (3a: IC₅₀ values of 51.3 and 77.6?nM; 3b: IC₅₀ values of 11.2 and 83.5?nM). Compounds 3a and 3b also exhibited increased hAChE inhibitory activity compared with tacrine by approximately 5- and 28-fold, respectively, and low neurotoxicity. Importantly, these compounds also had lower hepatotoxicity than tacrine. Based on these results, compounds 3a and 3b could be considered as potential lead compounds for the treatment of AD and other AChE related diseases, such as schizophrenia, glaucoma and myasthenia gravis.     

Molecular determinants for improved activity at PPARα: Structure–activity relationship of pirinixic acid derivatives,docking study and site-directed mutagenesis of PPARα

Peroxisome proliferator-activated receptors (PPARs) are attractive targets for the treatment of the metabolic syndrome. Especially a combination of PPARα and PPARγ agonistic activity seems worthwhile to be pursued. Herein we present the design and synthesis of a series of pirinixic acid derivatives as potent PPARα particularly dual PPARα/γ agonists with 2-((4-chloro-6-((4-(phenylamino)phenyl)amino)pyrimidin-2-yl)thio)octanoicacid having the highest potential. Our investigations based on molecular docking and structure–activity relationship (SAR) studies elucidated structural determinants affecting the potency at PPARα. A diphenylamine-scaffold seems to play a key role. Careful in silico analysis revealed an essential role for a hydrogen bond between the diphenylamine and a water cluster. We confirmed this hypothesis using a mutated PPARα LBD in our transactivation assay to disrupt the water cluster and to validate the proposed interaction.     

Structure–activity studies on the side chain of a simplified analog of aplysiatoxin (aplog-1) with anti-proliferative activity

We have recently developed a simplified analog of aplysiatoxin (aplog-1) as an activator of protein kinase C (PKC) with anti-proliferative activity like bryostain 1. To identify sites in aplog-1 that could be readily modified to optimize therapeutic performance and to develop a molecular probe for examining the analog’s mode of action, substituent effects on the phenol ring were systematically examined. Whereas hydrophilic acetamido derivatives were less active than aplog-1 in inhibiting cancer cell growth and binding to PKCδ, introduction of hydrophobic bromine and iodine atoms enhanced both biological activities. The anti-proliferative activity was found to correlate closely with molecular hydrophobicity, and maximal activity was observed at a log P value of 4.0–4.5. On the other hand, an induction test with Epstein–Barr virus early antigen demonstrated that these derivatives have less tumor-promoting activity in vitro than aplog-1 regardless of the hydrophobicity of their substituents. These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1.     

Morningness–eveningness and affective temperaments assessed by the Temperament Evaluation of Memphis,Pisa and San Diego-Autoquestionnaire (TEMPS-A)

Chronotype is a stable trait presenting one’s circardian preference. Since chronotype disturbances are common in patients with affective disorders, our aim is to evaluate chronotypes related to affective temperaments, measured with the temperament evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A). The study included 618 subjects (151 men and 467 women) within the framework of web-based design. They all fulfilled a questionnaire, consisting of the Composite Scale of Morningness (CSM), Sleep Wake Pattern Assessment Questionnaire (SWPAQ), and the TEMPS-A scale. Multiple regression models revealed that after controlling for age and gender: irritable and cyclothymic temperaments were negatively associated with total CSM score, CSM morning affect and circadian preference components, Sleepability (S), Vigilance (V), Wakeability (W) and positively with Morningness (M) and Eveningness (E) subscales of SWPAQ; anxious temperament was negatively associated with total CSM scores, CSM morning affect and with S, V, W subscales of SWPAQ; depressive temperament was negatively associated with Falling asleep, S, V, W subscales of SWPAQ; hyperthymic temperament was positively associated with CSM morning affect and V, W and negatively with M subscales of SWPAQ. The results show distinctiveness of the associations between hyperthymic temperament and circadian preferences, compared to all other TEMPS-A temperaments (depressive, cyclothymic, irritable and anxious). In the CMS scale, only hyperthymic temperament was related to morning affect. In the SWPAQ scale, hyperthymic temperament was the only one associated with earlier morningness (earlier wake up time preference), increased parameters of vigor – wakeability, vigilance, and also the only one not associated with decreased plasticity of circadian rhythm (sleepability and falling asleep). Results also point to some similarities between cyclothymic and irritable temperaments in some aspects of the chronotype.     

Evidence for the adaptive significance of enzyme activity levels: Interspecific variation in α-GPDH and ADH in Drosophila

The activity levels of alcohol dehydrogenase and -glycerophosphate dehydrogenase were compared among nine species of Drosophila representing three phylogenetic groups. For any given life stage, interspecific variability in activity level was much greater for ADH than for -GPDH. Patterns of ontogenetic expression of enzyme activity were also much more variable among species for ADH than for -GPDH. These results are consistent with the interpretation that -GPDH is involved with a relatively uniform adaptive function among species, whereas ADH levels may reflect variable adaptive capabilities. There is a significant correlation between ADH activities and survivorship on alcohol-treated media for these nine species.This research was supported by Contract AT(04-3)-34 200 with ERDA. The authors are supported by an NIH training grant in genetics.     

Analogues of the Inhoffen–Lythgoe diol with anti-proliferative activity

The anti-proliferative activity of a series of ester- and amide-linked Inhoffen–Lythgoe side chain analogues is reported. Whereas the Inhoffen–Lythgoe diol was inactive in these studies, a number of aromatic and aliphatic ester-linked side chains demonstrated modest in vitro growth inhibition in two human cancepar cell lines, U87MG (glioblastoma) and HT-29 (colorectal adenocarcinoma). Structure–activity relationship (SAR) studies demonstrated the most active aromatic (13) and aliphatic (25 and 29) substituted analogues were approximately equipotent in U87MG and HT-29 cells. Further evaluation of 13, 25, and 29 indicated these analogues do not activate canonical vitamin D signaling nor antagonize Hedgehog (Hh) signaling. Thus, the cellular mechanism(s) that govern the anti-proliferative activity for this class of truncated vitamin D-based structures appears to be different from classical mechanisms previously identified for these scaffolds.     

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Structure–activity relationship of the aryl region

The structure–activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1.     

Assessing the structure–activity relationships of fluorotelomer unsaturated acids and aldehydes with glutathione

Fluorotelomer alcohols (FTOHs) have been shown to degrade via abiotic and biotic mechanisms to perfluorocarboxylates (PFCAs) which are environmentally persistent and bioaccumulate in humans and wildlife depending on their chain length. Fluorotelomer unsaturated aldehydes (FTUALs) and acids (FTUCAs) are intermediate metabolites that form from the degradation of FTOHs. Their potential for toxicity is not yet defined and may be more significant compared to PFCAs. Past studies have shown that these intermediates form adducts with glutathione (GSH). The purpose of this study was to further assess the reactivity of these intermediate compounds. In vitro experiments were carried out in an aqueous buffer system (pH 7.4) where FTUCAs and FTUALs of varying chain lengths were reacted with GSH. To quantify the reactivity of FTUCAs and FTUALs, unreacted free GSH was derivatized with 5,5′-dithiobis(2-nitrobenzoic acid), its absorbance measured at 412 nm, and the percentage of unconjugated free GSH evaluated over time. EC₅₀ values were obtained for the reactions of GSH with acrolein and methyl methacrylate to assess the accuracy of the method, as well as for acrylic acid, FTUCAs, and FTUALs. The results of this study indicated that α,β-unsaturated aldehydes are comparatively the most reactive and reaction with GSH may be influenced by the length of the fluorinated tail. This is the first study to examine the relationship of FTUCAs and FTUALs with biological nucleophiles by quantifying their intrinsic reactivity.     

Complete mitochondrial genome of a new vole Proedromys liangshanensis (Rodentia: Cricetidae) and phylogenetic analysis with related species: are there implications for the validity of the genus Proedromys?

AIM. The complete mitochondrial genome sequence of a newly discovered vole, Proedromys liangshanensis (Rodentia: Cricetidae: Arvicolinae), was determined. RESULTS. The mitogenome of P. liangshanensis is 16,296 bp in length. As with most other mammals, it contains the same gene order and an identical number of genes or regions, including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one putative control region. The A+T content of the control region is 58.2%, the lowest proportion detected so far in Myomorpha. To confirm the phylogenetic position of P. liangshanensis, we carried out phylogenetic analyses based on complete mitochondrial genomic data using Bayesian, maximum parsimony, and maximum likelihood methods. CONCLUSION. All results revealed that P. liangshanenis is sister to Microtus. Although the results do not bear light on the validity of the genus Proedromys, based on the morphological characters, we suggest that Proedromys is an independent genus of equal rank to the genus Microtus.