bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer learning enables prediction ofCYP2D6haplotype function
Authors: McInnes Gregory , Dalton Rachel , Sangkuhl Katrin , Whirl-Carrillo Michelle , Lee Seung-been , Tsao Philip S. , Gaedigk Andrea , Altman Russ B. , Woodahl Erica L. 
Published: June 2019

AbstractCytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene whose protein product metabolizes more than 20% of clinically used drugs. Genetic variations inCYP2D6are responsible for interindividual heterogeneity in drug response that can lead to drug toxicity and ineffective treatment, makingCYP2D6one of the most important pharmacogenes. Prediction of CYP2D6 phenotype relies on curation of literature-derived functional studies to assign a functional status toCYP2D6haplotypes. As the number of large-scale sequencing efforts grows, new haplotypes continue to be discovered, and assignment of function is challenging to maintain. To address this challenge, we have trained a deep learning model to predict functional status ofCYP2D6haplotypes, called Hubble.2D6. We find that Hubble.2D6 predictsCYP2D6haplotype functional status with 88% accuracy in a held out test set and explains a significant amount of the variability inin vitrofunctional data. Hubble.2D6 may be a useful tool for assigning function to haplotypes with uncurated function, which may be used for screening individuals who are at risk of being poor metabolizers.
Mental Health, Schooling Attainment and Polygenic Scores: Are There Significant Gene-Environment Associations?
Authors: Amin Vikesh , Behrman Jere R. , Fletcher Jason M. , Flores Carlos A. , Flores-Lagunes Alfonso , Kohler Hans-Peter 
Published: June 2019

AbstractIt is well-established that (1) there is a large genetic component to mental health, and (2) higher schooling attainment is associated with better mental health. Given these two observations, we test the hypothesis that schooling may attenuate the genetic predisposition to poor mental health. Specifically, we estimate associations between a polygenic score (PGS) for depressive symptoms, schooling attainment and gene-environment (GxE) interactions with mental health (depressive symptoms and depression), in two distinct United States datasets at different adult ages-29 years old in the National Longitudinal Study of Adolescent Health (Add Health) and 54 years old in the Wisconsin Longitudinal Study (WLS). OLS results indicate that the association of the PGS with mental health is similar in Add Health and the WLS, but the association of schooling attainment is much larger in Add Health than in the WLS. There is some suggestive evidence that the association of the PGS with mental health is lower for more-schooled older individuals in the WLS, but there is no evidence of any significant GxE associations in Add Health. Quantile regression estimates also show that in the WLS the GxE associations are statistically significant only in the upper parts of the conditional depressive symptoms score distribution. We assess the robustness of the OLS results to omitted variable bias by using the siblings samples in both datasets to estimate sibling fixed-effect regressions. The sibling fixed-effect results must be qualified, in part due to low statistical power. However, the sibling fixed-effect estimates show that college education is associated with fewer depressive symptoms in both datasets.
MR-LDP: a two-sample Mendelian randomization for GWAS summary statistics accounting for linkage disequilibrium and horizontal pleiotropy
Authors: Cheng Qing , Yang Yi , Shi Xingjie , Yeung Kar-Fu , Yang Can , Peng Heng , Liu Jin 
Published: June 2019

AbstractThe proliferation of genome-wide association studies (GWAS) has prompted the use of two-sample Mendelian randomization (MR) with genetic variants as instrumental variables (IV) for drawing reliable causal relationships between health risk factors and disease outcomes. However, the unique features of GWAS demand that MR methods account for both linkage disequilibrium (LD) and ubiquitously existing horizontal pleiotropy among complex traits, which is the phenomenon wherein a variant affects the outcome through mechanisms other than exclusively through the exposure. Therefore, statistical methods that fail to consider LD and horizontal pleiotropy can lead to biased estimates and false-positive causal relationships. To overcome these limitations, we propose a probabilistic model for MR analysis to identify the casual effects between risk factors and disease outcomes using GWAS summary statistics in the presence of LD and to properly account for horizontal pleiotropy among genetic variants (MR-LDP). MR-LDP utilizes a computationally efficient parameter-expanded variational Bayes expectation-maximization (PX-VBEM) algorithm to estimate the parameter of interest and further calibrates the evidence lower bound (ELBO) for a likelihood ratio test. We then conducted comprehensive simulation studies to demonstrate the advantages of MR-LDP over the existing methods in terms of both type-I error control and point estimates. Moreover, we used two real exposure-outcome pairs (CAD-CAD and Height-Height; CAD for coronary artery disease) to validate the results from MR-LDP compared with alternative methods, showing that our method is more efficient in using all instrumental variants in LD. By further applying MR-LDP to lipid traits and body mass index (BMI) as risk factors for complex diseases, we identified multiple pairs of significant causal relationships, including a protective effect of high-density lipoprotein cholesterol (HDL-C) on peripheral vascular disease (PVD), and a positive causal effect of body mass index (BMI) on hemorrhoids.
Functional dissociation of theta oscillations in the frontal and visual cortices and their long-range network during sustained attention
Authors: Han Hio-Been , Lee Ka Eun , Choi Jee Hyun 
Published: June 2019

ABSTRACTTheta-band (4–12 Hz) activities in the frontal cortex have been thought to be a key mechanism of sustained attention and goal-related behaviors, forming a phase-coherent network with task-related sensory cortices for integrated neuronal ensembles. However, recent visual task studies found that selective attention attenuates stimulus-related theta power in the visual cortex, suggesting a functional dissociation of cortical theta oscillations. To investigate this contradictory behavior of cortical theta, a visual Go/No-Go task was performed with electroencephalogram recording in mice. During the No-Go period, transient theta oscillations were observed in both the frontal and visual cortices, but theta oscillations of the two areas were prominent in different trial epochs. By separating trial epochs based on subjects’ short-term performance, we found that frontal theta was prominent in good-performance epochs, while visual theta was prominent in bad-performance epochs, exhibiting a functional dissociation of cortical theta rhythms. Furthermore, the two theta rhythms also showed a heterogeneous pattern of phase-amplitude coupling with fast oscillations, reflecting their distinct architecture in underlying neuronal circuitry. Interestingly, in good-performance epochs, where visual theta was relatively weak, stronger fronto-visual long-range synchrony and shorter posterior-to-anterior temporal delay were found. These findings highlight a previously overlooked aspect of long-range synchrony between distinct oscillatory entities in the cerebral cortex and provide empirical evidence of a functional dissociation of cortical theta rhythms.IN BRIEFPrevious literature emphasized the pro-cognitive role of coherent oscillatory networks between distal brain regions, such as the fronto-visual theta synchrony. However, such a conceptual framework has been challenged as recent findings revealed distinct behavioral correlates of theta oscillations found in different cortical regions, especially in the frontal and visual cortices. Here, we show that frontal and visual theta represent distinct cortical processes and that the functional connectivity between them increases during sustained attention, especially when one of the two theta rhythms is relatively suppressed. The data presented here highlight a novel aspect of neural long-range synchrony between distinct cortical oscillators with distinct functional significance in task performance.
Unprecedented biomass and fatty acid production by the newly discovered cyanobacteriumSynechococcussp. PCC 11901
Authors: Włodarczyk Artur , Selão Tiago Toscano , Norling Birgitta , Nixon Peter J. 
Published: June 2019

AbstractCyanobacteria, which use solar energy to convert carbon dioxide into biomass, are potential solar biorefineries for the sustainable production of chemicals and biofuels. However, yields obtained with current strains are still uncompetitive compared to existing heterotrophic production systems. Here we report the discovery and characterization of a new cyanobacterial strain,Synechococcussp. PCC 11901, with potential for green biotechnology. It is transformable, has a short doubling time of ≈2 hours, grows at high light intensities and a wide range of salinities and accumulates up to 18.3 g dry cell weight/L of biomass – 2-3 times more than previously described for cyanobacteria - when grown in a modified medium containing elevated nitrate, phosphate and iron. As a proof of principle, PCC 11901 engineered to produce free fatty acids did so at unprecedented levels for cyanobacteria, with final yields reaching over 6 mM (1.5 g/L), comparable to those achieved by heterotrophic organisms.
Scop3P: a comprehensive resource of human phosphosites within their full context
Authors: Ramasamy Pathmanaban , Turan Demet , Tichshenko Natalia , Hulstaert Niels , Vandermarliere Elien , Vranken Wim , Martens Lennart 
Published: June 2019

AbstractProtein phosphorylation is a key post-translational modification (PTM) in many biological processes and is associated to human diseases such as cancer and metabolic disorders. The accurate identification, annotation and functional analysis of phosphosites is therefore crucial to understand their various roles. Phosphosites (P-sites) are mainly analysed through phosphoproteomics, which has led to increasing amounts of publicly available phosphoproteomics data. Several resources have been built around the resulting phosphosite information, but these are usually restricted to protein sequence and basic site metadata. What is often missing from these resources, however, is context, including protein structure mapping, experimental provenance information, and biophysical predictions. We therefore developed Scop3P: a comprehensive database of human phosphosites within their full context. Scop3P integrates sequences (UniProtKB/Swiss-Prot), structures (PDB), and uniformly reprocessed phosphoproteomics data (PRIDE) to annotate all known human phosphosites. Furthermore, these sites are put into biophysical context by annotating each phosphoprotein with perresidue structural propensity, solvent accessibility, disordered probability, and early folding information. Scop3P, available at https://iomics.ugent.be/scop3p, presents a unique resource for visualization and analysis of phosphosites, and for understanding of phosphosite structure-function relationships.
Dark diversity reveals importance of biotic resources and competition for plant diversity across broad environmental gradients
Authors: Fløjgaard Camilla , Valdez Jose W. , Dalby Lars , Moeslund Jesper Erenskjold , Clausen Kevin K. , Ejrnæs Rasmus , Pärtel Meelis , Brunbjerg Ane Kirstine 
Published: June 2019

AbstractSpecies richness is the most commonly used metric to quantify biodiversity. However, examining dark diversity, the group of missing species which can potentially inhabit a site, can provide a more thorough understanding of the processes influencing observed biodiversity and help evaluate the restoration potential of local habitats. So far, dark diversity has mainly been studied for specific habitats or largescale landscapes while less attention has been given to variation across broad environmental gradients or as a result of local conditions and biotic interactions. In this study, we investigate the importance of local environmental conditions in determining dark diversity and observed richness in plant communities across broad environmental gradients. We use the ecospace concept to investigate how abiotic gradients (defined as position), availability of biotic resources (defined as expansion), spatiotemporal extent of habitats (defined as continuity), as well as species interactions through competition, relate to these biodiversity measures. Position variables were important for both plant richness and dark diversity, some with quadratic relationships, e.g., plant richness showing a unimodal response to soil fertility corresponding to the intermediate productivity hypothesis. Competition represented by community mean Grime C showed a negative correlation with plant richness. Besides position, organic carbon was the most important variable for dark diversity, indicating that in late succession habitats such as forests and shrubs, dark diversity is generally low. The importance of Grime C indicate that intermediate disturbance, such as grazing, may facilitate higher species richness and lower dark diversity. Comparing various biodiversity metrics and their influencing factors might reveal important drivers of biodiversity changes and result in better conservation decision-making.
New genetic sources for orange color in cucumber (Cucumis sativus L.) fruit flesh
Authors: Waters Brian M. , Kim HaeJin , Amundsen Keenan 
Published: June 2019

AbstractMost cucumber varieties have fruits with white flesh, which is devoid of ß-carotene and has a low concentration of total carotenoids. Carotenoids are important nutrients for humans and animals. Thus, developing cucumber varieties with orange flesh could provide a new nutritionally enhanced food source. Some cucumbers with yellow and orange flesh have been described, but there are others that have not been studied. Here, we used three cucumber PI lines, reported to produce colored fruits, from the USDA National Plant Germplasm System to generate three F2populations. Fruits from the F2populations with colored flesh (green, yellow, or orange) were pooled, and an equal number of fruits with white flesh were pooled. RNA was isolated from the pools and used for RNA sequencing to determine gene expression differences and to identify SNPs in each pool. The orange color of the cucumber fruits was confirmed to be due to ß-carotene. There were no clear expression patterns for genes of the carotenoid biosynthesis pathway that would suggest that their expression controlled the coloration of fruits. Mutations in carotenoid biosynthesis genes also did not explain the variation. However, we detected a SNP in the homolog of theOrgene that is responsible for ß-carotene accumulation in orange cauliflower. This genetic basis is different from that of previously studied orange cucumbers, but our results suggest thatOris not the only factor. These results provide the basis for future studies for breeding orange cucumbers for commercial or home garden production.
Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder
Authors: Westacott Laura J. , Humby Trevor , Haan Niels , Brain Sophie A. , Bush Emma-Louise , Toneva Margarita , Baloc Andreea-Ingrid , Moon Anna L. , Reddaway Jack , Owen Michael J. , Hall Jeremy , Hughes Timothy R. , Morgan B. Paul , Gray William P. , Wilkinson Lawrence S. 
Published: June 2019

AbstractComplement is a key component of the immune system with roles in inflammation and host-defence. Here we reveal novel functions of complement pathways impacting on emotional reactivity of potential relevance to the emerging links between complement and risk for psychiatric disorder. We used mouse models to assess the effects of manipulating components of the complement system on emotionality. Mice lacking the complement C3a Receptor (C3aR-/-) demonstrated a selective increase in unconditioned (innate) anxiety whilst mice deficient in the central complement component C3 (C3-/-) showed a selective increase in conditioned (learned) fear. The dissociable behavioural phenotypes were linked to different signalling mechanisms. Effects on innate anxiety were independent of C3a, the canonical ligand for C3aR, consistent with the existence of an alternative ligand mediating innate anxiety, whereas effects on learned fear were due to loss of iC3b/CR3 signalling. Our findings show that specific elements of the complement system and associated signalling pathways contribute differentially to heightened states of anxiety and fear commonly seen in psychopathology.
FAAH, SLC6A4, and BDNF variants are not associated with psychosocial stress and mental health outcomes in a population of Syrian refugee youth
Authors: Clukay Christopher J. , Matarazzo Anthony , Dajani Rana , Hadfield Kristin , Panter-Brick Catherine , Mulligan Connie J. 
Published: June 2019

AbstractThe developmental origins of health and disease (DOHaD) hypothesis posits that early childhood stressors disproportionately impact adult health. Numerous studies have found adult mental health to be associated with childhood adversities and genetic variants, particularly in genes related to neurochemistry. However, few studies have examined the way interactive effects may manifest over time and fewer still include protective factors, like resilience. Our group has previously found associations between the monoamine oxidase A gene, MAOA, and a contextually-specific measure of resilience with a measure of perceived psychosocial stress over time in Syrian refugee youth. In this study, we work with the same sample of adolescents to test genetic variants in three additional candidate genes (FAAH, the 5-HTTLPR region of SLC6A4, and BDNF) for associations with six psychosocial stress and mental health outcomes. Using multi-level modeling, we find no association between variants in these candidate genes and psychosocial stress or mental health outcomes. Our analysis included tests for both direct genetic effects and interactions with lifetime trauma and resilience. Negative results, such as the lack of genetic associations with outcome measures, provides a more complete framework in which to better understand positive results and associations.
Monopoly behavior of China’s manufacturing enterprises
Authors: Wang Guidong 
Published: June 2019

Purpose
With the increase of state capital, corporate total factor productivity (TFP) has a tendency to jump up at first and then slowly decrease. Generally, no significant “productivity paradox” can be observed in China’s manufacturing industry. With the increase of export density, corporate TFP also shows a trend of initial jump growth and subsequent slow decline. This paper aims to discuss these issues.

Design/methodology/approach
Using the 1996–2013 China Industrial Enterprise Database, this paper studies the monopolistic behavior of Chinese manufacturing enterprises through the measurement of TFP and corporate monopoly power.

Findings
Results show that China’s manufacturing monopoly enterprises are generally innovation-oriented rather than rent-seeking. However, there are certain differences between diversified types of monopoly enterprises: the ones with state capital are more inclined to innovate than those without, whereas the ones with export delivery value are more inclined to seek rent than those without.

Originality/value
Therefore, the government should implement differentiated policies for diversified types of monopoly enterprises, and do so in a targeted manner fully reflecting the containment of rent-seeking and the encouragement of innovation.
Newtonian heat and mass conditions impact in thermally radiated Maxwell nanofluid Darcy–Forchheimer flow with heat generation
Authors: Waqas Muhammad , Gulzar M. Mudassar , Khan Waqar Azeem , Khan Muhammad Ijaz , Khan Niaz B. 
Published: June 2019

Purpose
This paper aims to elaborate the characteristics of magneto-Maxwell nanoliquid toward moving radiated surface. Flow analysis subject to Darcy–Forchheimer concept is studied. Newtonian heat/mass conditions and heat source aspects are taken into account for modeling. Apposite transformations are introduced for non-dimensionalization process.

Design/methodology/approach
Optimal homotopy analysis method is implemented to compute convergent solutions of nonlinear ordinary differential equations.

Findings
Temperature field increments when thermophoresis, heat generation and Brownian movement parameters are increased, whereas reverse situation is noticed for larger Prandtl number. The results also witness that concentration distribution has opposite characteristics for larger thermophoresis and Brownian movement parameters. Furthermore, the presented analysis reduces to traditional Darcy relation in the absence of local inertia coefficient.

Originality/value
As per the authors’ knowledge, no such analysis has been yet reported.
Understanding the emergence of entrepreneurial passion
Authors: Stenholm Pekka , Nielsen Mette Søgaard 
Published: June 2019

PurposeRecent research acknowledges entrepreneurial passion’s outcomes, but far less is known about how entrepreneurial passion comes about. In this study, the authors are interested in the emergence of entrepreneurial passion, and how competences and social network are associated with entrepreneurial passion. The paper aims to discuss these issues.Design/methodology/approachThe authors investigate whether entrepreneurial passion emerges out of socialisation, entrepreneurial experience or various combinations thereof. The authors tested the hypotheses on a data set of entrepreneurs who started their businesses with government financial support (n=1150).FindingsThe findings show that within a social environment, perceived emotional support is positively associated with entrepreneurial passion. Moreover, entrepreneurs’ task-related competence moderates this relationship positively. By investigating the emergence of entrepreneurial passion, the authors contribute to prior passion literature, which has mainly focused on its consequences.Originality/valueThe findings demonstrate both how entrepreneurial passion is associated with and how perceived emotional support can stem from unexpected sources, such as from a government-based start-up grant. For entrepreneurs, an increased awareness of passion’s emergence could better encourage them in their entrepreneurial endeavours. To people who are engaged in promoting entrepreneurship, our findings emphasise the symbolic and emotional aspects of instruments intended to support entrepreneurship.