bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA gastric cancer‐associated transcript 3 plays oncogenic roles in glioma through sponging miR‐3127‐5p
Authors: Pan Bailin , Zhao Ming , Xu Longbiao
Published: October 2018

Evidence is emerging that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. LncRNA gastric cancer‐associated transcript 3 (GACAT3) is reported to participate in the development of breast cancer, colorectal cancer, nonsmall cell lung cancer, and gastric cancer. However, whether it is implicated in glioma has not been elucidated. Here, we found that GACAT3 level was aberrantly elevated in glioma tissues and cell lines. Higher GACAT3 expression predicted lower survival rate. Knockdown of GACAT3 suppressed the proliferation, colony formation, migration, and invasion but promoting apoptosis in glioma cells. Next, we determined that GACAT3 contributes to glioma progression through inhibiting microRNA (miR)‐3127‐5p. Subsequently, ELAVL1 was identified as a direct target of miR‐3127‐5p by bioinformatics analysis and luciferase reporter assay. Moreover, we confirmed that GACAT3 promoted ELAVL1 expression through sponging miR‐3127‐5p, leading to glioma progression. Taken together, our study elucidated that GACAT3/miR‐3127‐5p/ELAVL1 signaling regulates glioma development and might be a promising therapeutic target.
Lipopolysaccharide‐induced proliferation and glycolysis in airway smooth muscle cells via activation of Drp1
Authors: Zhang Lixin , Ma Cui , Wang Xiaoying , He Siyu , Li Qian , Zhou Yutian , Liu Ying , Zhang Min , Yu Xiufeng , Zhao Xijuan , Li Fei , Zhu Da‐ling
Published: October 2018

Abnormal airway smooth muscle cells (ASMCs) proliferation is an important pathological process in airway remodeling contributes to increased mortality in asthma. Mitochondrial dynamics and metabolism have a central role in the maintenance of the cell function. In this study, lipopolysaccharide (LPS)‐induced ASMCs proliferative model was used to investigate the effect of mitochondria on the proliferation of ASMCs and the possible mechanism. We used cell and molecular biology to determine the effect of dynamin‐related protein 1 (Drp1) on LPS‐mediated ASMCs cell cycle progression and glycolysis. The major findings of the current study are as follows: LPS promoted an increased mitochondrial fission and phosphorylation of Drp1 at Ser616 (p‐Drp1 Ser616). LPS‐induced ASMCs proliferation and cell cycle progression, which was significantly inhibited application of Drp1 RNA interfering. Glycolysis inhibitor 2‐deoxyglucose (2‐DG) depressed ASMCs proliferative process induced by LPS stimulation. LPS caused mitochondrial metabolism disorders and aerobic glycolysis in a dependent on Drp1 activation. These results indicated that Drp1 may function as a key factor in asthma airway remodeling by mediating ASMC proliferation and cell cycle acceleration through an effect on mitochondrial metabolic disturbance.
Retracted: Resistin effects on pancreatic cancer progression and chemoresistance are mediated through its receptors CAP1 and TLR4
Authors: Zhang Min , Yan Li , Wang Gui‐Jie , Jin Ronghui
Published: October 2018

Resistin, secreted by macrophages in tumor microenvironment, has never been investigated in pancreatic cancer models, despite a vibrant tumor microenvironment around pancreatic tumors. We evaluated serum resistin levels in healthy individuals versus pancreatic cancer patients representing different tumor grades. In vitro mechanistic analysis involved MiaPaCa‐2 and SW1990 cells. Resistin signaling depends on binding of resistin to its cognitive receptors. Therefore, we silenced adenylyl cyclase‐associated protein 1 (CAP1) and toll‐like receptor 4 (TLR4), its two known receptors, individually as well as in combination, by short hairpin RNA (shRNA). Effect of resistin on cell proliferation, migration, invasion, cell cycle, and sensitivity to gemcitabine was studied without or with silencing of resistin receptors CAP1 and/or TLR4. The results were also confirmed in vivo in mice xenografted with MiaPaCa‐2 cells without or with receptor silencing. We report high resistin levels in pancreatic cancer patients which correlate positively with tumor grades. We observed a marked reduction in the resistin‐induced proliferation, migration, invasion, and cell cycle of pancreatic cancer cells MiaPaCa‐2 and SW1990 when the receptors were silenced. The results were confirmed in vivo wherein resistin effects were significantly attenuated in MiaPaCa‐2 xenografts with silenced receptors. The combined silencing of CAP1 and TLR4 was found to be most effective in vitro and in vivo. We found activation of STAT3 by resistin in vivo and in vitro which was dependent on the presence of CAP1 and TLR4. Further, resistin was found to induce resistance to gemcitabine through its receptors. Our results describe novel functional roles of resistin with implications toward a better understanding of pancreatic tumor microenvironment.
Fusion of quantitative imaging features and serum biomarkers to improve performance of computer‐aided diagnosis scheme for lung cancer: A preliminary study
Authors: Gong Jing , Liu Ji‐yu , Jiang Yao‐jun , Sun Xi‐wen , Zheng Bin , Nie Sheng‐dong
Published: October 2018

Objectives

To develop and test a new multifeature‐based computer‐aided diagnosis (CADx) scheme of lung cancer by fusing quantitative imaging (QI) features and serum biomarkers to improve CADx performance in classifying between malignant and benign pulmonary nodules.

Methods

First, a dataset involving 173 patients was retrospectively assembled, which includes computed tomography (CT) images and five serum biomarkers extracted from blood samples. Second, a CADx scheme using a four‐step–based semiautomatic segmentation method was applied to segment the targeted lung nodules, and compute 78 QI features from each segmented nodule from CT images. Third, two support vector machine (SVM) classifiers were built using QI features and serum biomarkers, respectively. SVM classifiers were trained and tested using the overall dataset with a Relief feature selection method, a synthetic minority oversampling technique and a leave‐one‐case‐out validation method. Finally, to further improve CADx performance, an information‐fusion method was used to combine the prediction scores generated by two SVM classifiers.

Results

Areas under receiver operating characteristic curves (AUC) generated by QI feature and serum biomarker‐based SVMs were 0.81 ± 0.03 and 0.69 ± 0.05, respectively. Using an optimal weighted fusion method to combine prediction scores generated by two SVMs, AUC value significantly increased to 0.85 ± 0.03 (P < 0.05).

Conclusions

This study demonstrates (a) higher CADx performance by using QI features than using the serum biomarkers and (b) feasibility of further improving CADx performance by fusion of QI features and serum biomarkers, which indicates that QI features and serum biomarkers contain the complementary classification information.
CSBFinder: discovery of colinear syntenic blocks across thousands of prokaryotic genomes
Authors: Svetlitsky Dina , Dagan Tal , Chalifa-Caspi Vered , Ziv-Ukelson Michal
Published: October 2018

Motivation

Identification of conserved syntenic blocks across microbial genomes is important for several problems in comparative genomics such as gene annotation, study of genome organization and evolution and prediction of gene interactions. Current tools for syntenic block discovery do not scale up to the large quantity of prokaryotic genomes available today.

Results

We present a novel methodology for the discovery, ranking and taxonomic distribution analysis of colinear syntenic blocks (CSBs)—groups of genes that are consistently located close to each other, in the same order, across a wide range of taxa. We present an efficient algorithm that identifies CSBs in large genomic datasets. The algorithm is implemented and incorporated in a novel tool with a graphical user interface, denoted CSBFinder, that ranks the discovered CSBs according to a probabilistic score and clusters them to families according to their gene content similarity. We apply CSBFinder to data mine 1487 prokaryotic genomes including chromosomes and plasmids. For post-processing analysis, we generate heatmaps for visualizing the distribution of CSB family members across various taxa. We exemplify the utility of CSBFinder in operon prediction, in deciphering unknown gene function and in taxonomic analysis of colinear syntenic blocks.

Availability and implementation

CSBFinder software and code are publicly available at https://github.com/dinasv/CSBFinder.

Supplementary information

Supplementary data are available at Bioinformatics online.
Multitasking in Nursing Homes: Differences Between For-Profit and Nonprofit Quality Outcomes
Authors: Gaudet Hefele Jennifer , Wang Xiao (Joyce) , Bishop Christine E , Barooah Adrita
Published: October 2018

Background and Objectives

Nursing homes (NHs) in the United States face increasing pressures to admit Medicare postacute patients, given higher payments relative to Medicaid. Changes in the proportion of residents who are postacute may initiate shifts in care practices, resource allocations, and priorities. Our study sought to determine whether increases in Medicare short-stay census have an impact on quality of care for long-stay residents.

Research Design and Methods

This study used panel data (2005–2010) from publicly-available sources (Nursing Home Compare, Area Health Resource File, LTCFocus.org) to examine the relationship between a 1-year change in NH Medicare census and 14 measures of long-stay quality among NHs that experienced a meaningful increase in Medicare census during the study period (N = 7,932). We conducted analyses on the overall sample and stratified by for- and nonprofit ownership.

Results

Of the 14 long-stay quality measures examined, only one was shown to have a significant association with Medicare census: increased Medicare census was associated with improved performance on the proportion of residents with pressure ulcers. Stratified analyses showed increased Medicare census was associated with a significant decline in performance on 3 of 14 long-stay quality measures among nonprofit, but not for-profit, facilities.

Discussion and Implications

Our findings suggest that most NHs that experience an increase in Medicare census maintain long-stay quality. However, this may be more difficult to do for some, particularly nonprofits. As pressure to focus on postacute care mount in the current payment innovation environment, our findings suggest that most NHs will be able to maintain stable quality.
Alterations in the amplitude and burst distribution of sensorimotor beta oscillations impair reward-dependent motor learning in anxiety
Authors: Sporn Sebastian , Hein Thomas P. , Ruiz María Herrojo
Published: October 2018

Anxiety results in sub-optimal motor performance and learning; yet, the precise mechanisms through which these modifications occur remain unknown. Using a reward-based motor sequence learning paradigm, we show that concurrent and prior anxiety states impair learning by biasing estimates about the hidden performance goal and the stability of such estimates over time (volatility). In an electroencephalography study, three groups of participants completed our motor task, which had separate phases for motor exploration (baseline) and reward-based learning. Anxiety was manipulated either during the initial baseline exploration phase or while learning. We show that anxiety induced at baseline reduced motor variability, undermining subsequent reward-based learning. Mechanistically, however, the most direct consequence of state anxiety was an underestimation of the hidden performance goal and a higher tendency to believe that the goal was unstable over time. Further, anxiety decreased uncertainty about volatility, which attenuated the update of beliefs about this quantity. Changes in the amplitude and burst distribution of sensorimotor and prefrontal beta oscillations were observed at baseline, which were primarily explained by the anxiety induction. These changes extended to the subsequent learning phase, where phasic increases in beta power and in the rate of long (> 500 ms) oscillation bursts following reward feedback were linked to smaller updates in predictions about volatility, with a higher anxiety-related increase explaining the biased volatility estimates. These data suggest that state anxiety alters the dynamics of beta oscillations during general performance, yet more prominently during reward processing, thereby impairing proper updating of motor predictions when learning in unstable environments.
BitMapperBS: a fast and accurate read aligner for whole-genome bisulfite sequencing
Authors: Cheng Haoyu , Xu Yun
Published: October 2018

As a gold-standard technique for DNA methylation analysis, whole-genome bisulfite sequencing (WGBS) helps researchers to study the genome-wide DNA methylation at single-base resolution. However, aligning WGBS reads to the large reference genome is a major computational bottleneck in DNA methylation analysis projects. Although several WGBS aligners have been developed in recent years, it is difficult for them to efficiently process the ever-increasing bisulfite sequencing data. Here we propose BitMapperBS, an ultrafast and memory-efficient aligner that is designed for WGBS reads. To improve the performance of BitMapperBS, we propose various strategies specifically for the challenges that are unique to the WGBS aligners, which are ignored in most existing methods. Our experiments on real and simulated datasets show that BitMapperBS is one order of magnitude faster than the state-of-the-art WGBS aligners, while achieves similar or better sensitivity and precision. BitMapperBS is freely available at https://github.com/chhylp123/BitMapperBS.
Rapid covalent-probe discovery by electrophile fragment screening
Authors: Resnick Efrat , Bradley Anthony , Gan Jinrui , Douangamath Alice , Krojer Tobias , Sethi Ritika , Aimon Anthony , Amitai Gabriel , Belini Dom , Bennett James , Fairhead Michael , Fedorov Oleg , Geurink Paul P. , Guo Jingxu , Plotnikov Alexander , Reznik Nava , Ruda Gian Filippo , Saez Laura Diaz , Straub Verena M. , Szommer Tamas , Velupillai Srikannathasan , Zaidman Daniel , Coker Alun R. , Dowson Christopher G. , Barr Haim , Huber Killian V.M. , Brennan Paul E. , Ovaa Huib , Delft Frank von , London Nir
Published: October 2018

Covalent probes can display unmatched potency, selectivity and duration of action, however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening. Such electrophilic fragments were considered non-selective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge, and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against ten cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. By contrast, we found selective hits for most targets. Combination with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2, and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile fragment screening as a practical and efficient tool for covalent ligand discovery.
CANDOCK: Chemical atomic network based hierarchical flexible docking algorithm using generalized statistical potentials
Authors: Fine Jonathan A , Konc Janez , Samudrala Ram , Chopra Gaurav
Published: October 2018

Small molecule docking has proven to be invaluable for drug design and discovery. However, existing docking methods have several limitations, such as, improper treatment of the interactions of essential components in the chemical environment of the binding pocket (e.g. cofactors, metal-ions, etc.), incomplete sampling of chemically relevant ligand conformational space, and the inability to consistently correlate docking scores of the best binding pose with experimental binding affinities. We present CANDOCK, a novel docking algorithm that utilizes a hierarchical approach to reconstruct ligands from an atomic grid using graph theory and generalized statistical potential functions to sample biologically relevant ligand conformations. Our algorithm accounts for protein flexibility, solvent, metal ions and cofactors interactions in the binding pocket that are traditionally ignored by current methods. We evaluate the algorithm on the PDBbind and Astex proteins to show its ability to reproduce the binding mode of the ligands that is independent of the initial ligand conformation in these benchmarks. Finally, we identify the best selector and ranker potential functions, such that, the statistical score of best selected docked pose correlates with the experimental binding affinities of the ligands for any given protein target. Our results indicate that CANDOCK is a generalized flexible docking method that addresses several limitations of current docking methods by considering all interactions in the chemical environment of a binding pocket for correlating the best docked pose with biological activity.
Dual prognostic role for 2-oxoglutarate oxygenases in ten diverse cancer types: Implications for cell cycle regulation and cell adhesion maintenance
Authors: Chang Wai Hoong , Forde Donall , Lai Alvina G.
Published: October 2018

Objectives

Tumor hypoxia is associated with metastasis and resistance to chemotherapy and radiotherapy. Genes involved in oxygen-sensing are clinically relevant and have significant implications on prognosis.

Methods

We identified of two signatures, signature 1 (good prognosis) and signature 2 (adverse prognosis), each consisting of 5 genes using three pancreatic cancer cohorts (n=681). We validated the signatures’ performance in predicting survival in ten cancers using Cox regression and receiver operating characteristic (ROC) analyses.

Results

Signature 1 and signature 2 were associated with good and poor overall survival respectively. Prognosis of signature 1 in 8 cohorts representing 6 cancers (n=2,627): bladder (hazard ratio [HR]=0.68, P=0.039), papillary renal cell (HR=0.35, P=0.013), liver (HR=0.64, P=0.033 and HR=0.49, P=0.025), lung (HR=0.66, P=0.014) and pancreatic (HR=0.42, P<0.001 and HR=0.64, P=0.04) and endometrial (HR=0.40, P<0.001). Prognosis of signature 2 in 12 cohorts representing 9 cancers (n=4,134): bladder (HR=1.46, P=0.039), cervical (HR=1.97, P=0.035), head and neck (HR=1.39, P=0.038), renal clear cell (HR=1.47, P=0.012), papillary renal cell (HR=3.89, P=0.0015), liver (HR=5.10, P<0.0001 and HR=2.26, P<0.001), lung (HR=1.54, P=0.011), pancreatic (HR=2.09, P=0.002, HR=1.46, P=0.018, and HR=1.99, P<0.0001) and stomach (HR=1.78, P=0.004). Multivariate Cox regression confirmed independent clinical relevance of signatures in these cancers. ROC analyses confirmed superior performance of signatures to current tumor staging benchmarks. KDM8 is a potential tumor suppressor downregulated in liver and pancreatic cancers and is an independent prognostic factor. KDM8 expression negatively correlated with cell cycle regulators. Low KDM8 in tumors was associated with loss of cell adhesion phenotype through HNF4A signaling.

Conclusions

Pan-cancer signatures of oxygen-sensing genes used for risk assessment in 10 cancers (n=6,761) could guide individualized treatment plans.
Asi1 regulates the distribution of proteins at the inner nuclear membrane inSaccharomyces cerevisiae
Authors: Smoyer Christine J. , Smith Sarah E. , McCroskey Scott , Unruh Jay R. , Jaspersen Sue L.
Published: October 2018

Inner nuclear membrane (INM) protein composition regulates nuclear function, affecting processes such as gene expression, chromosome organization, nuclear shape and stability. Mechanisms that drive changes in the INM proteome are poorly understood in part because it is difficult to definitively assay INM composition rigorously and systematically. Using a split-GFP complementation system to detect INM access, we examined the distribution of all C-terminally taggedSaccharomyces cerevisiaemembrane proteins in wild-type cells and in mutants affecting protein quality control pathways, such as INM-associated degradation (INMAD), ER-associated degradation (ERAD) and vacuolar proteolysis. Deletion of the E3 ligase Asi1 had the most pronounced effect on the INM compared to mutants in vacuolar or ER-associated degradation pathways, consistent with a role for Asi1 in the INMAD pathway. Our data suggests that Asi1 not only removes mis-targeted proteins at the INM, but it also controls the levels and distribution of native INM components, such as the membrane nucleoporin Pom33. Interestingly, loss of Asi1 does not affect Pom33 protein levels but instead alters Pom33 distribution in the NE through Pom33 ubiquitination, which drives INM redistribution. Taken together, our data demonstrate that the Asi1 E3 ligase has a novel function in INM protein regulation in addition to protein turnover.
The whale shark genome reveals how genomic and physiological properties scale with body size
Authors: Park Seung Gu , Luria Victor , Weber Jessica A. , Jeon Sungwon , Kim Hak-Min , Jeon Yeonsu , Bhak Youngjune , Jun Jehun , Kim Sang Wha , Hong Won Hee , Lee Semin , Cho Yun Sung , Karger Amir , Cain John W. , Manica Andrea , Kim Soonok , Kim Jae-Hoon , Edwards Jeremy S. , Bhak Jong , Church George M.
Published: October 2018

The endangered whale shark (Rhincodon typus) is the largest fish on Earth and is a long-lived member of the ancient Elasmobranchii clade. To characterize the relationship between genome features and biological traits, we sequenced and assembled the genome of the whale shark and compared its genomic and physiological features to those of 81 animals and yeast. We examined scaling relationships between body size, temperature, metabolic rates, and genomic features and found both general correlations across the animal kingdom and features specific to the whale shark genome. Among animals, increased lifespan is positively correlated to body size and metabolic rate. Several genomic features also significantly correlated with body size, including intron and gene length. Our large-scale comparative genomic analysis uncovered general features of metazoan genome architecture: GC content and codon adaptation index are negatively correlated, and neural connectivity genes are longer than average genes in most genomes. Focusing on the whale shark genome, we identified multiple features that significantly correlate with lifespan. Among these were very long gene length, due to large introns highly enriched in repetitive elements such as CR1-like LINEs, and considerably longer neural genes of several types, including connectivity, activity, and neurodegeneration genes. The whale shark’s genome had an expansion of gene families related to fatty acid metabolism and neurogenesis, with the slowest evolutionary rate observed in vertebrates to date. Our comparative genomics approach uncovered multiple genetic features associated with body size, metabolic rate, and lifespan, and showed that the whale shark is a promising model for studies of neural architecture and lifespan.
A robust nonlinear low-dimensional manifold for single cell RNA-seq data
Authors: Verma Archit , Engelhardt Barbara E.
Published: October 2018

Modern developments in single cell sequencing technologies enable broad insights into cellular state. Single cell RNA sequencing (scRNA-seq) can be used to explore cell types, states, and developmental trajectories to broaden understanding of cell heterogeneity in tissues and organs. Analysis of these sparse, high-dimensional experimental results requires dimension reduction. Several methods have been developed to estimate low-dimensional embeddings for filtered and normalized single cell data. However, methods have yet to be developed for unfiltered and unnormalized count data. We present a nonlinear latent variable model with robust, heavy-tailed error and adaptive kernel learning to estimate low-dimensional nonlinear structure in scRNA-seq data. Gene expression in a single cell is modeled as a noisy draw from a Gaussian process in high dimensions from low-dimensional latent positions. This model is called the Gaussian process latent variable model (GPLVM). We model residual errors with a heavy-tailed Student’s t-distribution to estimate a manifold that is robust to technical and biological noise. We compare our approach to common dimension reduction tools to highlight our model’s ability to enable important downstream tasks, including clustering and inferring cell developmental trajectories, on available experimental data. We show that our robust nonlinear manifold is well suited for raw, unfiltered gene counts from high throughput sequencing technologies for visualization and exploration of cell states.
On the unfounded enthusiasm for soft selective sweeps II: examining recent evidence from humans, flies, and viruses
Authors: Harris Rebecca B. , Sackman Andrew , Jensen Jeffrey D.
Published: October 2018

Since the initial description of the genomic patterns expected under models of positive selection acting on standing genetic variation and on multiple beneficial mutations—so-called soft selective sweeps—researchers have sought to identify these patterns in natural population data. Indeed, over the past two years, large-scale data analyses have argued that soft sweeps are pervasive across organisms of very different effective population size and mutation rate—humans, Drosophila, and HIV. Yet, others have evaluated the relevance of these models to natural populations, as well as the identifiability of the models relative to other known population-level processes, arguing that soft sweeps are likely to be rare. Here, we look to reconcile these opposing results by carefully evaluating three recent studies and their underlying methodologies. Using population genetic theory, as well as extensive simulation, we find that all three examples are prone to extremely high false-positive rates, incorrectly identifying soft sweeps under both hard sweep and neutral models. Furthermore, we demonstrate that well-fit demographic histories combined with rare hard sweeps serve as the more parsimonious explanation. These findings represent a necessary response to the growing tendency of invoking parameter-heavy, assumption-laden models of pervasive positive selection, and neglecting best practices regarding the construction of proper demographic null models.
Screening performance of abbreviated versions of the UPSIT smell test
Authors: Joseph Theresita , Auger Stephen D. , Peress Luisa , Rack Daniel , Cuzick Jack , Giovannoni Gavin , Lees Andrew , Schrag Anette E. , Noyce Alastair J.
Published: October 2018

Background

Hyposmia features in several neurodegenerative conditions, including Parkinson’s disease (PD). The University of Pennsylvania Smell Identification Test (UPSIT) is a widely used screening tool for detecting hyposmia, but is time-consuming and expensive when used on a large scale.

Methods

We assessed shorter subsets of UPSIT items for their ability to detect hyposmia in 891 healthy participants from the PREDICT-PD study. Established shorter tests included Versions A and B of both the 4-item Pocket Smell Test (PST) and 12-item Brief Smell Identification Test (BSIT). Using a data-driven approach, we evaluated screening performances of 23,231,378 combinations of 1-7 smell items from the full UPSIT.

Results

PST Versions A and B achieved sensitivity/specificity of 76.8%/64.9% and 86.6%/45.9% respectively, whilst BSIT Versions A and B achieved 83.1%/79.5% and 96.5%/51.8% for detecting hyposmia defined by the longer UPSIT. From the data-driven analysis, two optimised sets of 7 smells surpassed the screening performance of the 12 item BSITs (with validation sensitivity/specificities of 88.2%/85.4% and 100%/53.5%). A set of 4 smells (Menthol, Clove, Gingerbread and Orange) had higher sensitivity for hyposmia than PST-A, -B and even BSIT-A (with validation sensitivity 91.2%). The same 4 smells also featured amongst those most commonly misidentified by 44 individuals with PD compared to 891 PREDICT-PD controls and a screening test using these 4 smells would have identified all hyposmic patients with PD.

Conclusion

Using abbreviated smell tests could provide a cost-effective means of screening for hyposmia in large cohorts, allowing more targeted administration of the UPSIT or similar smell tests.
A multi-parent recombinant inbred line population ofCaenorhabditis elegansenhances mapping resolution and identification of novel QTLs for complex life-history traits
Authors: Snoek Basten L. , Volkers Rita J.M. , Nijveen Harm , Petersen Carola , Dirksen Philipp , Sterken Mark G. , Nakad Rania , Riksen Joost , Rosenstiel Philip , Stastna Jana J. , Braeckman Bart P. , Harvey Simon C. , Schulenburg Hinrich , Kammenga Jan E.
Published: October 2018

Local populations of the bacterivorous nematodeCaenorhabditis eleganscan be genetically almost as diverse as global populations. To investigate the effect of local genetic variation on heritable traits, we developed a new recombinant inbred line (RIL) population derived from four wild isolates. The wild isolates were collected from two closely located sites in France: Orsay and Santeuil. By crossing these four genetically diverse parental isolates a population of 200 RILs was constructed. RNA-seq was used to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the four genotypes with an average spacing of 11 kb, possibly doubling the mapping resolution relative to currently available RIL panels. The SNPs were used to construct a genetic map to facilitate QTL analysis. Life history traits, such as lifespan, stress resistance, developmental speed and population growth were measured in different environments. For most traits substantial variation was found, and multiple QTLs could be detected, including novel QTLs not found in previous QTL analysis, for example for lifespan or pathogen responses. This shows that recombining genetic variation acrossC. eleganspopulations that are in geographical close proximity provides ample variation for QTL mapping. Taken together, we show that RNA-seq can be used for genotyping, that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates permits analysis of local adaptation and life history trade-offs.
Dynamics of spontaneous alpha activity correlate with language ability in young children
Authors: Kwok Elaine Y. L. , Cardy Janis Oram , Allman Brian L. , Allen Prudence , Herrmann Björn
Published: October 2018

Early childhood is a period of tremendous growth in both language ability and brain maturation. To understand the dynamic interplay between neural activity and spoken language development, we used resting-state EEG recordings to explore the relation between alpha oscillations (7–10 Hz) and oral language ability in 4- to 6-year-old children with typical development (N=41). Three properties of alpha oscillations were investigated: a) alpha power using spectral analysis, b) flexibility of the alpha frequency quantified via the oscillation’s moment-to-moment fluctuations, and c) scaling behavior of the alpha oscillator investigated via the long-range temporal correlation in the alpha-amplitude time course. All three properties of the alpha oscillator correlated with children’s oral language abilities. Higher language scores were correlated with lower alpha power, greater flexibility of the alpha frequency, and longer temporal correlations in the alpha-amplitude time course. Our findings demonstrate a cognitive role of several properties of the alpha oscillator that has largely been overlooked in the literature.

Graphical Abstract
Social isolation-induced epigenetic and transcriptional changes inDrosophiladopaminergic neurons
Authors: Agarwal Pavan , Chung Phuong , Heberlein Ulrike , Kent Clement
Published: October 2018

Epigenetic mechanisms play fundamental roles in brain function and behavior and stressors such as social isolation can alter animal behavior via epigenetic mechanisms. However, due to cellular heterogeneity, identifying cell-type-specific epigenetic changes in the brain is challenging. Here we report first use of a modified INTACT method in behavioral epigenetics ofDrosophila: a method we call mini-INTACT. Using ChIP-seq on mini-INTACT purified dopaminergic nuclei, we identified epigenetic signatures in socially-isolated and socially-enrichedDrosophilamales. Social experience altered the epigenetic landscape in clusters of genes involved in transcription and neural function. Some of these alterations were predicted by expression changes of four transcription factors and the prevalence of their binding sites in several clusters. These transcription factors were previously identified as activity-regulated genes and their knockdown in dopaminergic neurons reduced the effects of social experience on sleep. Our work enables the use ofDrosophilaas a model for cell-type-specific behavioral epigenetics.
Foreign R&D satellites as a medium for the international diffusion of knowledge
Authors: Blit Joel
Published: October 2018

I examine the extent to which foreign R&D satellites of multinational firms act as a medium for the international diffusion of knowledge. Using patents from the United States Patent and Trademark Office, I compare the frequency with which headquarters patents are cited by third‐party firms in the satellite's host country relative to a control group of patents, and this both before and after the establishment of the satellite (using a difference‐in‐differences approach). The results suggest that the satellite increases the flow of knowledge from the multinational's headquarters to firms in the satellite's host country. This satellite effect on knowledge diffusion is largest in host countries and sectors with strong but not world‐class capabilities that have both the motivation and absorptive capacity to learn from foreign parties. The findings also suggest that knowledge diffusion is greatest when satellites are staffed with inventors that have previously either patented with other local firms (thus having stronger local social networks) or with the headquarters (thus having headquarters knowledge).
An economic and environment friendly way of recycling boron carbide waste to prepare B4C/Al composite ceramic
Authors: Gao Shuaibo , Dong Kaizhao , Li Xin , Kong Jian , Wang Shuai , Xing Pengfei , Li Pan
Published: October 2018

Recently, with the rapid growth of sapphire wafer applications, boron carbide as abrasive, has shown an increasing demand. Great amounts of boron carbide waste (low purity and small grain size with D50 ≈ 1 μm) are therefore produced during the production of boron carbide abrasives and barely recovered and utilized. This paper is aimed at developing an economic and environment friendly process to recycle the boron carbide waste through adding a certain amount of Al powder to prepare B4C/Al composite ceramic. Prior to the sintering process, samples were firstly mixed with different Al powder and then pelleted and dehydrated. The effects of the pelletizing factors on performances of the pellets and the ceramics were optimized as binder hydroxypropyl methylcellulose addition 0.4%, pelleting pressure 30 MPa, Al addition 9 wt%, sintering time 90 minutes. Under these conditions, the apparent porosity, bulk density, compressive strength and flexural strength of the sintered B4C/Al are 19.08%, 1.84 g/cm3, 246.88 MPa and 71.10 MPa respectively. Al addition can not only attribute to the low‐temperature liquid sintering and densification of the product, but also generation of some stable phases including AlB12, AlB12C2 and Al3BC, which in turn increase the performance of the ceramic composite.
Modification of commercial boron carbide powder using Rapid Carbothermal Reduction
Authors: Toksoy Muhammet Fatih , Haber Richard A.
Published: October 2018

Non‐uniform morphology and existence of free carbon are two main problems for commercial boron carbide powders. This work proposes a method for eliminating free carbon and changing the morphology of commercial powders using Rapid Carbothermal Reduction (RCR) process. Free carbon is eliminated from commercial boron carbide powders and morphology is evolved to less angular shapes with limited particle size growth. Commercial and modified powders were densified by Spark Plasma Sintering at 1900°C with 0, 5, and 20 minutes dwell. Despite the particle size growth, modified boron carbide powders reached >99%TDwith shorter dwell times compared with commercial starting powders. Improved microhardness observed with dense modified samples as a result of enhanced morphology and increased twinning.
Electrically conductive SiC ceramics processed by pressureless sintering
Authors: Kim Yong‐Hyeon , Kim Young‐Wook , Kim Kwang Joo
Published: October 2018

Polycrystalline SiC ceramics with 10 vol% Y2O3‐AlN additives were sintered without any applied pressure at temperatures of 1900‐2050°C in nitrogen. The electrical resistivity of the resulting SiC ceramics decreased from 6.5 × 101 to 1.9 × 10−2 Ω·cm as the sintering temperature increased from 1900 to 2050°C. The average grain size increased from 0.68 to 2.34 μm with increase in sintering temperature. A decrease in the electrical resistivity with increasing sintering temperature was attributed to the grain‐growth‐induced N‐doping in the SiC grains, which is supported by the enhanced carrier density. The electrical conductivity of the SiC ceramic sintered at 2050°C was ~53 Ω−1·cm−1 at room temperature. This ceramic achieved the highest electrical conductivity among pressureless liquid‐phase sintered SiC ceramics.
Assembly of β‐SiC Nanowires film and humidity sensing performance
Authors: Shen Xiulin , Liu Haitao , Liu Silin , Huang Zhaohui , Liu Yangai , Fang Minghao , Wu Xiaowen , Min Xin
Published: October 2018

β‐SiC materials have been seen as the third‐generation semiconductor widely used in kinds of photoelectric device, high temperature electronics, and other fields. Compared with ordinary semiconductors, β‐SiC materials have huge potential application in replacing monocrystalline silicon in extreme environments because of their numerals extraordinary chemical and physical properties. Based on this, β‐SiC nanowires obviously are more desirable in any way. Here, we present a modified chemical vapor deposition (CVD) method to synthesis β‐SiC nanowires, which needs no protect gas, and transfer it to Si/SiO2 substrates equipped with Au electrodes. The microstructure of the as‐prepared samples is tested by field emission scanning electron microscopy (FESEM). The humidity sensing performance of electronic device is measured by electrochemical workstation test equipment. It shows that the resistance of β‐SiC nanowires increases with increasing environment humidity within very short response/recovery time‐0.5 seconds/0.5 seconds and also performs excellent cycling stability. Such advantage superiorities make it highly possible to apply β‐SiC nanowires into various environments.
Systems vaccinology and big data in the vaccine development chain
Authors: Raeven René H. M. , van Riet Elly , Meiring Hugo D. , Metz Bernard , Kersten Gideon F. A.
Published: October 2018

Systems vaccinology has proven a fascinating development in the last decade. Where traditionally vaccine development has been dominated by trial and error, systems vaccinology is a tool that provides novel and comprehensive understanding if properly used. Data sets retrieved from systems‐based studies endorse rational design and effective development of safe and efficacious vaccines. In this review we first describe different omics‐techniques that form the pillars of systems vaccinology. In the second part, the application of systems vaccinology in the different stages of vaccine development is described. Overall, this review shows that systems vaccinology has become an important tool anywhere in the vaccine development chain.
No evidence of quantitative signal honesty across species of aposematic burnet moths (Lepidoptera: Zygaenidae)
Authors: Briolat Emmanuelle S. , Zagrobelny Mika , Olsen Carl E. , Blount Jonathan D. , Stevens Martin
Published: October 2018

Many defended species use conspicuous visual warning signals to deter potential predators from attacking. Traditional theory holds that these signals should converge on similar forms, yet variation in visual traits and the levels of defensive chemicals is common, both within and between species. It is currently unclear how the strength of signals and potency of defences might be related: conflicting theories suggest that aposematic signals should be quantitatively honest, or, in contrast, that investment in one component should be prioritized over the other, while empirical tests have yielded contrasting results. Here, we advance this debate by examining the relationship between defensive chemicals and signal properties in a family of aposematic Lepidoptera, accounting for phylogenetic relationships and quantifying coloration from the perspective of relevant predators. We test for correlations between toxin levels and measures of wing colour across 14 species of day‐flying burnet and forester moths (Lepidoptera: Zygaenidae), protected by highly aversive cyanogenic glucosides, and find no clear evidence of quantitative signal honesty. Significant relationships between toxin levels and coloration vary between sexes and sampling years, and several trends run contrary to expectations for signal honesty. Although toxin concentration is positively correlated with increasing luminance contrast in forewing pattern in 1 year, higher toxin levels are also associated with paler and less chromatically salient markings, at least in females, in another year. Our study also serves to highlight important factors, including sex‐specific trends and seasonal variation, that should be accounted for in future work on signal honesty in aposematic species.
Cargo‐dependent and cell wall‐associated xylem transport in Arabidopsis
Authors: Endo Satoshi , Iwai Yumi , Fukuda Hiroo
Published: October 2018

Sap molecules are transported by xylem flow throughout the whole plant body. Factors regulating the xylem transport of different molecules remain to be identified.

We used fluorophores to visualize xylem transport from roots to leaves in Arabidopsis thaliana. Several previously established Arabidopsis lines with modified xylem cell walls were used to determine the contribution of xylem cell walls to xylem transport.

Fluorophores underwent xylem flow‐dependent transport from roots to leaves within 20 min. A comparison of rhodamine, fluorescein and three fluorescently labeled CLV3/ESR‐related (CLE) peptides revealed cargo‐dependent xylem transport patterns in terms of leaf position and vein order. Only minor changes in amino acid sequence were sufficient to alter the xylem transport patterns of the labeled CLE peptides. We found that the xylem transport pattern of fluorescein was affected in Arabidopsis lines with modified AtXYN1, LAC4 or CCoAOMT1 expression. In these lines, application of a defense inducer, pipecolic acid, to roots resulted in altered defense response patterns in leaves, whereas all the lines showed wild‐type‐like responses when pipecolic acid was sprayed onto leaves.

The combined results reveal a finely controlled cargo‐dependent xylem transport and suggest that the xylem cell wall structure is crucial for this transport system.
A nodule‐localized phosphate transporter GmPT7 plays an important role in enhancing symbiotic N2 fixation and yield in soybean
Authors: Chen Liyu , Qin Lu , Zhou Lili , Li Xinxin , Chen Zhichang , Sun Lili , Wang Wenfei , Lin Zhihao , Zhao Jing , Yamaji Naoki , Ma Jian Feng , Gu Mian , Xu Guohua , Liao Hong
Published: October 2018

Symbiotic nitrogen (N2) fixation plays a vital role in sustainable agriculture. Efficient N2 fixation requires various materials, including phosphate (Pi); however, the molecular mechanism underlying the transport of Pi into nodules and bacteroids remains largely unknown.

A nodule‐localized Pi transporter, GmPT7, was functionally characterized in soybean (Glycine max) and its role in N2 fixation and yield was investigated via composite and whole transgenic plants.

GmPT7 protein was localized to the plasma membrane and showed transport activity for Pi in yeast. Altered expression of GmPT7 changed 33Pi uptake from rhizosphere and translocation to bacteroids. GmPT7 was mainly localized to the outer cortex and fixation zones of the nodules. Overexpression of GmPT7 promoted nodulation, and increased plant biomass, shoot nitrogen and phosphorus content, resulting in improved soybean yield by up to 36%. Double suppression of GmPT5 and GmPT7 led to nearly complete elimination of nodulation and over 50% reduction in plant biomass, shoot nitrogen and phosphorus content, indicating that both GmPT7 and GmPT5 contribute to Pi transport for N2 fixation.

Taken together, our results indicate that GmPT7 is a transporter responsible for direct Pi entry to nodules and further to fixation zones, which is required for enhancing symbiotic N2 fixation and grain yield of soybean.
Detection of genuine grass pollen sensitization in children by skin testing with a recombinant grass pollen hybrid
Authors: Douladiris Nikolaos , Garib Victoria , Focke‐Tejkl Margit , Valenta Rudolf , Papadopoulos Nikolaos G. , Linhart Birgit
Published: October 2018

Background

Skin testing represents a commonly used first diagnostic method in clinical practice, but allergen extracts may vary in composition and often contain cross‐reactive allergens and therefore do not always allow the precise identification of the sensitizing allergen source. Our aim was to investigate the suitability of a single recombinant hybrid molecule, consisting of the four major timothy grass pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Phl p 6) for in vivo diagnosis of genuine grass pollen allergy in children suffering from pollinosis.

Methods

Sixty‐four children aged from 6 to 17 years with a positive skin reaction and/or specific IgE to grass pollen extract and respiratory symptoms of pollinosis as well as 9 control children with allergy to other allergen sources were studied. SPT was performed with the recombinant hybrid, the four recombinant timothy grass pollen allergens, and grass pollen extract. Specific IgE reactivity to 176 micro‐arrayed allergen molecules was determined using ImmunoCAP ISAC technology. IgE reactivity to the hybrid was detected by non‐denaturing RAST‐based dot blot assay.

Results

Genuine grass pollen sensitization was confirmed in 94% of the children with positive SPT to grass pollen extract by SPT and IgE reactivity to the hybrid. The four hybrid‐negative children showed IgE reactivity to cross‐reactive allergens such as Phl p 4, Phl p 11, and Phl p 12 and had also sensitizations to pollen allergens from unrelated plants.

Conclusions

The recombinant hybrid molecule represents a useful tool for in vivo diagnosis of genuine grass pollen sensitization.