We review recent developments in the study of culture and personality measurement. Three approaches are described: an etic approach that focuses on establishing measurement equivalence in imported ...measures of personality, an emic (indigenous) approach that studies personality in specific cultures, and a combined emic-etic approach to personality. We propose the latter approach as a way of combining the methodological rigor of the etic approach and the cultural sensitivity of the emic approach. The combined approach is illustrated by two examples: the first with origins in Chinese culture and the second in South Africa. The article ends with a discussion of the theoretical and practical implications of the combined emic-etic approach for the study of culture and personality and for psychology as a science. (Contains 1 footnote.)
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
The German-British laser-interferometric gravitational wave detector GEO 600 is in its 14th year of operation since its first lock in 2001. After GEO 600 participated in science runs with other ...first-generation detectors, a program known as GEO-HF began in 2009. The goal was to improve the detector sensitivity at high frequencies, around 1 kHz and above,with technologically advanced yet minimally invasive upgrades. Simultaneously, the detector would record science quality data in between commissioning activities. As of early 2014, all of the planned upgrades have been carried out and sensitivity improvements of up to a factor of four at the high-frequency end of the observation band have been achieved. Besides science data collection, an experimental program is ongoing with the goal to further improve the sensitivity and evaluate future detector technologies. We summarize the results of the GEO-HF program to date and discuss its successes and challenges.
Few studies have examined the associations between sleep duration, shiftwork, and exercise to the infrequent menstruation, hyperandrogenism, and ovarian morphological changes observed in women with ...polycystic ovarian syndrome (PCOS).
To examine whether lifestyle factors, including short sleep duration, insufficient exercise, and shiftwork, alone or in combination, are associated with the reproductive and metabolic abnormalities typical of PCOS in a healthy population.
Prospective cross-sectional study of 231 women, including healthcare workers recruited for an annual health screen, healthy referral patients from the Women's Clinic and volunteers from the university community at the National University Hospital, Singapore, from 2011 to 2015.
The women completed a questionnaire, including their menstrual cycle length, sleep length, frequency of exercise and shift work. Hyperandrogenism (hirsutism score, testosterone, sex hormone binding globulin (SHBG)), ovarian morphology and function (anthral follicle count, ovarian volume, anti-mullerian hormone (AMH)), and metabolic measures (body mass index (BMI), waist hip ratio (WHR), blood pressure, fasting glucose, fasting insulin and fasting lipids) were examined through anthropometric measurements, transvaginal ultrasound scans, and blood tests.
No significant associations were observed between shift work, exercise or sleep duration and the androgenic and ovarian measures that define PCOS. However, women reporting fewer than 6 hours of sleep were more likely to report abnormal (short or long) menstrual cycle lengths (OR = 2.1; 95% CI, 1.1 to 4.2). Women who reported fewer than 6 hours of sleep had increased fasting insulin levels (difference in means = 2.13; 95% CI, 0.27 to 3.99 mU/L) and higher odds of insulin resistance (OR = 2.58; CI, 1.16 to 5.76). Lack of regular exercise was associated with higher mean fasting insulin (difference in means = 2.3 mU/L; 95% CI, 0.5 to 4.1) and HOMA-IR (difference in means = 0.49; 95% CI, 0.09 to 0.90) levels.
Women with insufficient sleep are at increased risk of menstrual disturbances and insulin resistance, but do not have the hyperandrogenism and polycystic ovarian morphology typical of PCOS.
Improved sleep duration may help reduce the risks of diabetes or infertility. Shift work, exercise or sleep duration appear not to impact the androgenic and ovarian measures that define PCOS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Objective To determine the strain-induced signaling pathways involved in regulating the transactivation of the transcription regulator Cbp/p300 Interacting Transactivator with ED-rich tail 2 ...(CITED2) and downstream targets in chondrocytes. Methods Primary human chondrocytes or C28/I2 chondrocytic cells were subjected to various strain regimes. C57BL/6 mice were subjected to treadmill running. Loss-of-function was carried out using siRNA or inhibitors specific for targeted molecules. mRNA levels were assayed by RT-qPCR, and proteins by western blotting, immunofluorescence, and/or immunohistochemical staining. CITED2 promoter activity was assayed in chondrocytes using wild-type or mutant constructs. Results Cyclic strain at 5%, 1 Hz induced CITED2 expression and suppressed expression of matrix metalloproteinase (MMP)-1 and -13 at the messenger RNA (mRNA) and protein levels in human chondrocytes. Abolishing primary cilia through knockdown of intraflagellar transport protein (IFT88) attenuated CITED2 gene expression and decreased protein levels. Similar effects were observed with inhibitors of extracellular adenosine triphosphate (ATP) or P2 purinergic receptors, or antagonists of Ca2+ signaling. Knockdown of IFT88 in articular chondrocytes in vivo diminished treadmill induced-CITED2 expression and upregulated MMPs. Knockdown of hypoxia-inducible factor (HIF)1α, specificity protein 1 (Sp1), or deletion of the shear stress response element (SSRE) in the CITED2 promoter limited cyclic strain-induced transactivation of CITED2. However, the strain induced-transactivation of CITED2 was abolished only on knockdown of HIF1α, Sp1, and SSRE or by loss-of-function of IFT88 or extracellular-signal-regulated kinases (ERK)1/2. Conclusions CITED2 transactivation is a critical event in signaling generated by strain and transduced by primary cilia, extracellular ATP, P2 purinergic receptors, and Ca2+ signaling. Strain-induced CITED2 transactivation requires HIF1α, Sp1, and an intact SSRE and leads to the downregulation of MMPs such as MMP-1 and MMP-13.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Congenital long QT syndrome (LQT) is a group of cardiac disorders associated with the dysfunction of cardiac ion channels. It is characterized by prolongation of the QT-interval, episodes of syncope ...and even sudden death. Individuals may remain asymptomatic for most of their lives while others present with severe symptoms. This heterogeneity in phenotype makes diagnosis difficult with a greater emphasis on more targeted therapy. As a means of understanding the molecular mechanisms underlying LQT syndrome, evaluating the effect of modifier genes on disease severity as well as to test new therapies, the development of model systems remains an important research tool. Mice have predominantly been the animal model of choice for cardiac arrhythmia research, but there have been varying degrees of success in recapitulating the human symptoms; the mouse cardiac action potential (AP) and surface electrocardiograms exhibit major differences from those of the human heart. Against this background, the zebrafish is an emerging vertebrate disease modelling species that offers advantages in analysing LQT syndrome, not least because its cardiac AP much more closely resembles that of the human. This article highlights the use and potential of this species in LQT syndrome modelling, and as a platform for the in vivo assessment of putative disease-causing mutations in LQT genes, and of therapeutic interventions.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Retinal degenerative diseases are a leading cause of blindness worldwide with debilitating life-long consequences for the affected individuals. Cell therapy is considered a potential future clinical ...intervention to restore and preserve sight by replacing lost photoreceptors and/or retinal pigment epithelium. Development of protocols to generate retinal tissue from human pluripotent stem cells (hPSC), reliably and at scale, can provide a platform to generate photoreceptors for cell therapy and to model retinal disease in vitro. Here, we describe an improved differentiation platform to generate retinal organoids from hPSC at scale and free from time-consuming manual microdissection steps. The scale up was achieved using an agarose mould platform enabling generation of uniform self-assembled 3D spheres from dissociated hPSC in microwells. Subsequent retinal differentiation was efficiently achieved via a stepwise differentiation protocol using a number of small molecules. To facilitate clinical translation, xeno-free approaches were developed by substituting Matrigel™ and foetal bovine serum with recombinant laminin and human platelet lysate, respectively. Generated retinal organoids exhibited important features reminiscent of retinal tissue including correct site-specific localisation of proteins involved in phototransduction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The role of fibroblast growth factor-2 (FGF-2) in maintaining undifferentiated human embryonic stem cells (hESC) was investigated using a targeted phosphoproteomics approach to specifically profile ...tyrosine phosphorylation events following FGF-2 stimulation. A cumulative total number of 735 unique tyrosine phosphorylation sites on 430 proteins were identified, by far the largest inventory to date for hESC. Early signaling events in FGF-2 stimulated hESC were quantitatively monitored using stable isotope dimethyl labeling, resulting in temporal tyrosine phosphorylation profiles of 316 unique phosphotyrosine peptides originating from 188 proteins. Apart from the rapid activation of all four FGF receptors, trans-activation of several other receptor tyrosine kinases (RTKs) was observed as well as induced tyrosine phosphorylation of downstream proteins such as PI3-K, MAPK and several Src family members. Both PI3-K and MAPK have been linked to hESC maintenance through FGF-2 mediated signaling. The observed activation of the Src kinase family members by FGF-2 and loss of pluripotent marker expression post Src kinase inhibition may point to the regulation of cytoskeletal and actin depending processes to maintain undifferentiated hESC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plant developmental dynamics can be heritable, genetically correlated with fitness and yield, and undergo selection. Therefore, characterizing the mechanistic connections between the genetic ...architecture governing plant development and the resulting ontogenetic dynamics of plants in field settings is critically important for agricultural production and evolutionary ecology. We use hierarchical Bayesian Function-Valued Trait (FVT) models to estimate Brassica rapa growth curves throughout ontogeny, across two treatments, and in two growing seasons. We find genetic variation for plasticity of growth rates and final sizes, but not the inflection point (transition from accelerating to decelerating growth) of growth curves. There are trade-offs between growth rate and duration, indicating that selection for maximum yields at early harvest dates may come at the expense of late harvest yields and vice versa. We generate eigengene modules and determine which are co-expressed with FVT traits using a Weighted Gene Co-expression Analysis. Independently, we seed a Mutual Rank co-expression network model with FVT traits to identify specific genes and gene networks related to FVT. GO-analyses of eigengene modules indicate roles for actin/cytoskeletal genes, herbivore resistance/wounding responses, and cell division, while MR networks demonstrate a close association between metabolic regulation and plant growth. We determine that combining FVT Quantitative Trait Loci (QTL) and MR genes/WGCNA eigengene expression profiles better characterizes phenotypic variation than any single data type (i.e. QTL, gene, or eigengene alone). Our network analysis allows us to employ a targeted eQTL analysis, which we use to identify regulatory hotspots for FVT. We examine cis vs. trans eQTL that mechanistically link FVT QTL with structural trait variation. Colocalization of FVT, gene, and eigengene eQTL provide strong evidence for candidate genes influencing plant height. The study is the first to explore eQTL for FVT, and specifically do so in agroecologically relevant field settings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
T cell homeostasis and functional responsiveness require signals from self-peptide-major histocompatibility complex (self-pMHC) and cytokines, but the mechanisms controlling this signal integration ...are unknown. Using a conditional deletion of the T cell lineage-specific protein Themis, we show that Themis is required for the maintenance of peripheral CD8
T cells and for proliferative CD8
T cell responses to low-affinity pMHC aided by cytokines. Themis-deficient peripheral T cells show a phenotype indicative of reduced tonic signaling from self-pMHC, strongly suggesting that Themis is a positive regulator of T cell receptor signal strength in response to low-affinity self-pMHC in peripheral T cells. Signals from low-affinity pMHC and cytokines synergistically induce phosphorylation of the kinase Akt, metabolic changes and c-Myc transcription factor induction in CD8
T cells only in the presence of Themis. This function of Themis is mediated through Shp1 phosphatase, as peripheral Themis and Shp1 double deletion rescues the peripheral CD8
T cell maintenance.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and ...treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analyzed exhaled breath samples from 277 participants presenting acute cardiorespiratory exacerbations and aged-matched healthy volunteers. Topological data analysis phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes (acute heart failure, acute asthma, acute chronic obstructive pulmonary disease, and community-acquired pneumonia). A multibiomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example, selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs.
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