Miracle-dz/UniFAR-FTUs huggingface dataset:
Edinburgh Research Explorer Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with Excitement-Seeking.

The tendency to seek stimulating activities and intense sensations deﬁne excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry ( N ¼ 7860), and combined the results in a meta-analysis. We identiﬁed a genome-wide signiﬁcant association between the Excitement-Seeking scale and rs7600563 ( P ¼ 2 (cid:2) 10 (cid:3) 8 ). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 ( CTNNA2 ) gene, which encodes for a brain-expressed a -catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples ( N ¼ 5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders.
Sociology of Childhood

The sociology of childhood has been used increasingly as a theoretical perspective in early childhood education since the late 1980s. In Australia, those who draw on the sociology of childhood have tended to use it in similar ways to European counterparts, being guided by six major tenets identified by Prout and James (1997) that form the basis of the sociology of childhood. These include the notion that childhood is a social construction, that childhood is a variable of social analysis and is closely connected to other variables such as class and gender, and that children's relationships and cultures are worthy of study in their own right (p. 8). Further, children are considered as active (rather than passive) agents in their daily lives and to be competent and knowledgeable about their own lives (p. 8). Although the sociology of childhood is comparatively young, there has been little analysis of the key tenets of the position. Morss is an exception and raises some fundamental issues for consideration, which include refining the notion of the 'socially constructed child', a term that is used widely in much that written about the sociology of childhood.
Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome

Introduction In autoimmune atypical hemolytic uremic syndrome (aHUS), the complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homolog complement FH-related protein 1 (CFHR1). The functional consequence of FH-blockade is widely established; however, the molecular basis of autoantibody binding and the role of CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1. Methods Eight anti-FH positive aHUS patients were enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies. We confirmed the location of the mapped epitopes using recombinant FH domains 19–20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1. Results We identified three linear epitopes on FH (aa1157–1171; aa1177–1191; and aa1207–1226) and one on CFHR1 (aa276–290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177–1191 on FH and aa276–290 on CFHR1, despite seven of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183–1198 in line with published observations. Summary According to the results, the linear epitopes we identified are located close to each other on the crystal structure of FH domains 19–20. This tertiary configuration contains the amino acids reported to be involved in C3b and sialic acid binding on the regulator, which may explain the functional deficiency of FH in the presence of autoantibodies. The data we provide identify the exact structures involved in autoantibody recruitment on FH and confirm the presence of an autoantibody binding epitope on CFHR1.
PENGARUH KECOCOKAN ETIKA TERHADAP KEPUASANKERJA, KOMITMEN ORGANISASI,DAN KEINGINAN PINDAHPADA KANTOR AKUNTAN PUBLIKDI M.AKASSAR

Penelitian ini meneliti penganth kecocokan etika pada kepuasan kerja, komitment organisasi, serta sikap pekerja untuk keluar/pindah dari pekerjaannya. Tujuan dari penelitian ini untuk menguji secara empiris apakah kecocokan etika mempenganihi kepuasan kerja, kecocokan etika mempengaruhi komitmen terhadap organisasi, serta keocokan etika mempengaruhi tingkat keinginan berpindah. Pada penelitian ini responden diminta untuk menjawab empat item instrumen pertanyaan yaitu 20 item pertanyaan untuk kecocokan etika, 20 item untuk kepuasan kerja, 16 item pertanyaan komitmen, serta 5 item pertanyaan keinginan untuk pindah. Dalam pengujian hipotesa yang digunakan dalam penelitian ini yaitu dengan menggunakan persamaan regresi biasa yang dilakukan secara parsial. Hasil penelitian terdahulu yang dimana semakin tinggi kecocokan etika berpengaruh terhadap kepuasan kerja, begitu juga dengan komitment organisasi, dan tidak berpengaruh terhadap keinginan untuk pindah. Hasil penelitian ini menunjukkan bahwa dengan tingkat kecocokan etika yang tinggi mempunyai hubungan negatif kepada kepuasan kerja dan signifikan, sedangkan komitment organisasi berpengaruh positif dan signifikan. Begitu pula dengan tingkat kecocokan etika yang tinggi dengan sendirinya tidak ada keinginan untuk pindah.This research is examining the influence of the climate ethic to the working satisfaction, commitment to the organization, and also to the worker's attitude to quit, or move from their job. The aim of this examination is to put an empirical test whether the climate ethic influence the working satisfaction, the climate ethic influence the commitment to the organization, also if the climate satisfaction influence the desire to move or quit job. In this research the respondent were asked to answer four main question instrument which are 20 items of question concerning about the climate ethic, 20 items about the working satisfaction, 16 items of question about the commitment, as well as 5 items of question about the desire to move. In the hypothesis test which is use within the examination by using the usual regression equality which is conduct partially. The previous research, where the higher the climate ethic influence the working satisfaction, also to the commitment to the organization, and had no influence on the desire to move their jobs. This research indicate that with the high level of climate ethic has a negative correlation to the working satisfaction, and significant, while the commitment to the organization has the positive influence and significant. As well with the high level of climate ethic it is taken for granted there is no desires to move from their jobs.
Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA

Indolicidin, a l3-residue antimicrobial peptide-amide, which is unusually rich in tryptophan and proline, is isolated from the cytoplasmic granules of bovine neutrophils. In this study, the structures of indolicidin in 50% D3-trifluoroethanol and in the absence and presence of SDS and D38-dodecylphosphocholine were determined using NMR spectroscopy. Multiple conformations were found and were shown to be due to different combinations of contact between the two WPW motifs. Although indolicidin is bactericidal and able to permeabilize bacterial membranes, it does not lead to cell wall lysis, showing that there is more than one mechanism of antimicrobial action. The structure of indolicidin in aqueous solution was a globular and amphipathic conformation, differing from the wedge shape adopted in lipid micelles, and these two structures were predicted to have different functions. Indolicidin, which is known to inhibit DNA synthesis and induce filamentation of bacteria, was shown to bind DNA in gel retardation and fluorescence quenching experiments. Further investigations using surface plasmon resonance confirmed the DNA-binding ability and showed the sequence preference of indolicidin. Based on our biophysical studies and previous results, we present a diagram illustrating the DNA-binding mechanism of the antimicrobial action of indolicidin and explaining the roles of the peptide when interacting with lipid bilayers at different concentrations.
The role of proline residues in the structure and function of human MT2 melatonin receptor

Abstract: Melatonin functions as an essential regulator of various physiological processes in all vertebrate species. In mammals, two G protein‐coupled melatonin receptors (GPCR) mediate some melatonin’s actions: MT1 and MT2. Transmembrane domains (TM) of most GPCRs contain a set of highly conserved proline residues that presumably play important structural and functional roles. As TM segments of MT2 receptor display several interesting differences in expression of specific proline residues compared to other rhodopsin‐like receptors (rGPCRs), we investigated the role of proline residues in the structure and function of this receptor. All prolines in TM segments of MT2 receptor were individually replaced with alanine and/or glycine. In addition, the unusual NAxxY motif located in TM7 was mutated to generate highly conserved NPxxY motif found in the majority of rGPCR proteins. Following transient expression in CHO‐K1 cells, binding properties of the mutant receptors and their ability to transduce signals were analyzed using 125I‐mel‐ and [35S]GTPγS‐binding assays, respectively. The impact of the performed mutations on the receptor structure was assessed by molecular dynamic simulations of MT2 receptors embedded in the fully hydrated phospholipid bilayer. Our results indicate that residues P174, P212 and P266 are important for the ligand binding and/or signaling of the human MT2 receptor. We also show that changes within the unusual NAxxY sequence in the TM7 (mutations A305P and A305V) produce defective MT2 receptors indicating an important role of this motif in the function of melatonin receptors.
Vitamin D Deficiency and Cardiometabolic Risks: A Juxtaposition of Arab Adolescents and Adults

The recent exponential surge in vitamin D research reflects the global epidemic of vitamin D deficiency and its potential impact on several chronic diseases in both children and adults. Several subpopulations, including Arab adolescent boys and girls, remain understudied. This study aims to fill this gap. A total of 2225 apparently healthy Saudi adolescents (1187 boys and 1038 girls, aged 13-17 years old) and 830 adults (368 men and 462 women, aged 18-50 years old) were respectively recruited from different public schools and medical practices within Riyadh, Saudi Arabia. Anthropometrics were taken and fasting blood samples withdrawn to examine serum glucose and lipid profile by routine analysis and 25-hydroxyvitamin D by ELISA. Almost half of the girls (47.0%) had vitamin D deficiency as compared to only 19.4% of the boys (p<0.001), 36.8% of the adult women and 17.7% of the adult men (p<0.001). Furthermore, in boys there were more significant inverse associations between serum 25(OH)vitamin D levels and cardiometabolic indices than girls, while in contrast women had more significant associations than men. Vitamin D deficiency was significantly associated with diabetes mellitus type 2 (DMT2) [OR 3.47 (CI1.26-5.55); p<0.05] and pre-DM [OR 2.47 (CI 1.48-4.12); p<0.01] in boys. Furthermore, vitamin D insufficiency was significantly associated with abdominal obesity in boys [OR 2.75 (CI 1.1-7.1); p<0.05]. These associations for DMT2 and abdominal obesity were not observed in adult males, girls and adult women. Vitamin D deficiency/insufficiency and hyperglycemia is high among Arab adolescents. Vitamin D deficiency is mostly associated with cardiometabolic risk factors in adolescent Arab boys. This indicates a sex- and age-related disadvantage for boys with low vitamin D status and challenges the extra-skeletal protection of vitamin D correction in adolescent females.
Polymer coating behavior of Rayleigh-SAW resonators with gold electrode structure for gas sensor applications

Results from systematic polymer coating experiments on surface acoustic wave (SAW) resonators and coupled resonator filters (CRF) on ST-cut quartz with a corrosion-proof electrode structure entirely made of gold (Au) are presented and compared with data from similar SAW devices using aluminium (Al) electrodes. The recently developed Au devices are intended to replace their earlier Al counterparts in sensor systems operating in highly reactive chemical gas environments. Solid parylene C and soft poly[chlorotrifluoroethylene-co-vinylidene fluoride] (PCFV) polymer films are deposited under identical conditions onto the surface of Al and Au devices. The electrical performance of the Parylene C coated devices is monitored online during film deposition. The PCVF coated devices are evaluated after film deposition. The experimental data show that the Au devices can stand up to 40% thicker solid films for the same amount of loss increase than the Al devices and retain better resonance and phase characteristics. The frequency sensitivities of Au and Al devices to parylene C deposition are nearly identical. After coating with soft PCFV sensing film, the Au devices provide up to two times higher gas sensitivity when probed with cooling agent, octane, or tetrachloroethylene
Peptide Ligands Incorporated into the Threefold Spike Capsid Domain to Re-Direct Gene Transduction of AAV8 and AAV9 In Vivo

Efficiency and specificity of viral vectors are vital issues in gene therapy. Insertion of peptide ligands into the adeno-associated viral (AAV) capsid at receptor binding sites can re-target AAV2-derived vectors to alternative cell types. Also, the use of serotypes AAV8 and -9 is more efficient than AAV2 for gene transfer to certain tissues in vivo. Consequently, re-targeting of these serotypes by ligand insertion could be a promising approach but has not been explored so far. Here, we generated AAV8 and -9 vectors displaying peptides in the threefold spike capsid domain. These peptides had been selected from peptide libraries displayed on capsids of AAV serotype 2 to optimize systemic gene delivery to murine lung tissue and to breast cancer tissue in PymT transgenic mice (PymT). Such peptide insertions at position 590 of the AAV8 capsid and position 589 of the AAV9 capsid changed the transduction properties of both serotypes. However, both peptides inserted in AAV8 did not result in the same changes of tissue tropism as they did in AAV2. While the AAV2 peptides selected on murine lung tissue did not alter tropism of serotypes 8 and -9, insertion of the AAV2-derived peptide selected on breast cancer tissue augmented tumor gene delivery in both serotypes. Further, this peptide mediated a strong but unspecific in vivo gene transfer for AAV8 and abrogated transduction of various control tissues for AAV9. Our findings indicate that peptide insertion into defined sites of AAV8 and -9 capsids can change and improve their efficiency and specificity compared to their wild type variants and to AAV2, making these insertion sites attractive for the generation of novel targeted vectors in these serotypes.
Gardner‐Silengo‐Wachtel or genito‐palato‐cadiac syndrome with associated autosomal aneuploidy

Gardner‐Silengo‐Wachtel or genito‐palato‐cardiac syndrome is a disorder of male (46,XY) gonadal dysgenesis, thought to be either an X‐linked recessive or an autosomal recessive disorder. The propositus in our report presented with multiple congenital anomalies including micrognathia, cleft palate, congenital heart defect with D‐transposition, double outlet right ventricle, PFO, VSD, PDA and pulmonary valve stenosis and gonadal dysgenesis. Chromosome analysis showed a 46, XY, t(1;7)(q32,q22.1) der(10) t(3;10) (q21;q26)pat karyotype. This represents a rare case of autosomal aneuploidy associated with Gardner‐Silengo‐Wachtel or genito‐palato‐cardiac syndrome and suggests genetic heterogeneity for this syndrome. Partial monosomy of 10q also shares many of the prominent features of genito‐palato‐cardiac syndrome, including gonadal dysgenesis, cardiac defects and facial features. Monosomy for distal 10q may present as a phenocopy of Gardner‐Silengo‐Wachtel or genito‐palato‐cardiac syndrome. Alternatively, unmasking of a recessive allele on distal 10q may result in genito‐palato‐cardiac syndrome, thus potentially localizing a candidate region for the gene to 10q26 → qter. © 2009 Wiley‐Liss, Inc.
Intensive care physicians’ and nurses’ perception that hand hygiene prevents pathogen transmission: Belief strength and associations with other cognitive factors

Besides habituation, conscious decision-making remains important for healthcare workers’ hand hygiene compliance. This study compared 307 physicians and 348 nurses in intensive care at a German university medical centre regarding their belief that hand disinfection prevents pathogen transmission. Physicians perceived less risk reduction (p < 0.001; variance explained: 4%), a comparison outscored only by lower self-rated guideline knowledge (8%). In both groups, the transmission-preventive belief was associated with high response efficacy, behavioural intention and self-efficacy, but not with self-rated knowledge. Consistent with the Health Action Process Approach, hand hygiene interventions targeting risk reduction beliefs may promote high motivation, but not action control.
Assessment of glaucomatous changes in subjects with high myopia using spectral domain optical coherence tomography.

PURPOSE To evaluate the diagnostic ability to detect glaucoma in highly myopic eyes using spectral domain-optical coherence tomography (SD-OCT) parameters in a cross-sectional comparative study. METHODS A total of 82 patients with high myopia (≤-5 D) presented between April 2008 and August 2009. Subjects comprised 31 participants with high myopia but not perimetric glaucoma (no glaucoma group) and 51 patients with high myopia and concomitant perimetric glaucoma (glaucoma group). Ganglion cell complex (GCC), circumpapillary retinal nerve fiber layer (p-RNFL), and disc configuration parameters were obtained from algorithms of the SD-OCT system and subsequently compared. Receiver operating characteristics curves were constructed for each measurement parameter, and areas under the curves (AUCs) were compared. RESULTS All optic nerve fiber head, except disc area, and GCC parameters differed significantly between groups (P < 0.05). The largest AUCs from disc configuration, circumpapillary RNFL, and GCC parameters were 0.844 (C/D vertical), 0.826 (RNFL average), and 0.954 (global loss volume [GLV]), respectively. GLV was significantly better for detecting perimetric glaucoma than both the C/D vertical and RNFL average (P < 0.05). CONCLUSIONS All algorithms of the OCT system were useful for discriminating glaucoma. Among these, GCC measurements offered the best parameters for the clinical diagnosis of glaucoma in patients with high myopia and concomitant perimetric glaucoma.
Physiological roles of endogenous neurosteroids at α2 subunit-containing GABAA receptors

Neurosteroids are important endogenous modulators of the major inhibitory neurotransmitter receptor in the brain, the γ-amino-butyric acid type A (GABAA) receptor. They are involved in numerous physiological processes, and are linked to several central nervous system disorders, including depression and anxiety. The neurosteroids allopregnanolone and allo-tetrahydro-deoxy-corticosterone (THDOC) have many effects in animal models (anxiolysis, analgesia, sedation, anticonvulsion, antidepressive), suggesting they could be useful therapeutic agents, for example in anxiety, stress and mood disorders. Neurosteroids potentiate GABA-activated currents by binding to a conserved site within α subunits. Potentiation can be eliminated by hydrophobic substitution of the α1Q241 residue (or equivalent in other α isoforms). Previous studies suggest that α2 subunits are key components in neural circuits affecting anxiety and depression, and that neurosteroids are endogenous anxiolytics. It is therefore possible that this anxiolysis occurs via potentiation at α2 subunit-containing receptors. To examine this hypothesis, α2Q241M knock-in mice were generated, and used to define the roles of α2 subunits in mediating effects of endogenous and injected neurosteroids. Biochemical and imaging analyses indicated that relative expression levels and localization of GABAA receptor α1-α5 subunits were unaffected, suggesting the knock-in had not caused any compensatory effects. Electrophysiological characterization of cells in hippocampal and nucleus accumbens brain slices revealed faster-decaying inhibitory synaptic transmission in α2Q241M mice. Furthermore, the response to applied THDOC was markedly reduced compared to wild-type cells. α2 subunits therefore formed a major component of synaptic GABAA receptors in these areas. The α2Q241M knock-ins showed greater anxiety levels in two classical rodent anxiety paradigms (light-dark box and elevated plus maze), consistent with endogenous neurosteroids mediating anxiolysis via α2-type GABAA receptors. In addition, the anxiolytic response to injected THDOC is impaired by the α2Q241M mutation, which would identify the α2 isoform as an appropriate target for generating receptor subtype-selective neurosteroid therapeutics for anxiety disorders.
Does richness lose its luster? Effects of extensive practice on semantic richness in visual word recognition

Previous studies have reported facilitatory effects of semantic richness on word recognition (e.g., Yap et al., 2012). These effects suggest that word meaning is an important contributor to lexical decision task (LDT) performance, but what are the effects of repeated LDT practice on these semantic contributions? The current study utilized data from the British Lexicon Project (BLP) in which 78 participants made lexical decision judgments for 28,730 words over 16 h. We used linear mixed effects to detect practice-driven changes in the explanatory variance accounted for by a set of lexical predictors that included numerous indices of relative semantic richness, including imageability, the number of senses and average radius of co-occurrence (ARC). Results showed that practice was associated with decreasing effects of predictors such as word frequency and imageability. In contrast, ARC effects were only slightly diminished with repeated practice, and effects of the number of senses and the age of acquisition were unaffected by practice. We interpret our results within a framework in which variables may dynamically influence lexical processing and the post-lexical decision making mechanisms that also contribute to LDT performance.