bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple-serotype models of dengue virus transmission: simulation study and perspectives for the application of inference in epidemiological surveillance
Authors: Souto-Maior Caetano 
Published: March 2019

AbstractWith around 3 billion people at risk, dengue virus is endemic to many parts of the world. In the Brazilian city of Rio de Janeiro, surveillance measures require notification of new dengue virus cases, and are supplemented by serum collection from patients and sequencing of viral RNA. Phylogenetic analyses have been performed for all serotypes circulating in the country to identify viral genotypes, potentially identify new introductions, and compare viruses presently circulating in the country with those in the past, and of other countries. As a separate type of analysis, a number of mathematical models have been developed to describe dengue virus transmission – particularly qualitative incidence or prevalence patterns – although few have been tested. In this chapter, I show how different mathematical formulations could represent transmission of dengue virus by mosquitoes to humans, how the different model structures entail assumptions about the process, and how these affect outputs qualitatively. Inference from simulated data is used as proof of principle that the kind of data available could be used to accurately estimate all model parameters; however, it is shown that stochasticity may severely hamper efforts to test the models quantitatively. I further implement inference from sequence data for the different models, and compare the performance to that of time series. The methods are applied to the data available for the city of Rio de Janeiro.
The NEDD8 cycle controlled by NEDP1 upon DNA damage is a regulatory module of the HSP70 ATPase activity
Authors: Bailly Aymeric P. , Perrin Aurelien , Serrano-Macia Marina , Maghames Chantal , Leidecker Orsolya , Trauchessec Helene , Martinez-Chantar ML , Gartner Anton , Xirodimas Dimitris P. 
Published: March 2019

SummaryUbiquitin and ubiquitin-like chains are finely balanced by the action of conjugating and de-conjugating enzymes. Alterations in this balance trigger signalling events required for the response to stress conditions and are often observed in pathologies. How such changes are detected is not well-understood. We show that upon DNA damage the induction of the de-NEDDylating enzyme NEDP1 restricts the formation of poly-NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerisation and apoptosis induction, a step that requires the HSP70 ATPase activity. We found that HSP70 binds to NEDD8 and in vitro, mono-NEDD8 stimulates the ATPase activity of HSP70, counteracted upon poly-NEDDylation. This effect is independent of NEDD8 conjugation onto substrates. The studies identify the HSP70 chaperone as sensor of changes in the NEDD8 cycle, providing mechanistic insights for a cytoplasmic role of NEDD8 in the DNA damage induced apoptosis. They also indicate that the balance between mono- versus poly-NEDDylation is a regulatory module of HSP70 function. The above findings may be important in tumorigenesis, as we find that NEDP1 levels are downregulated in Hepatocellular Carcinoma with concomitant accumulation of NEDD8 conjugates.
Understanding the population structure of the GHQ-12: evidence for multidimensionality using Bayesian and Exploratory Structural Equation Modelling from a large-scale UK population survey
Authors: Griffith Gareth J , Jones Kelvyn 
Published: March 2019

AbstractMental health and its complexity, measurement and social determinants are increasingly important avenues of research for social scientists. Quantitative social science commonly investigates mental health as captured by population screening metrics. One of the most common of these metrics is the 12-Item General Health Questionnaire (GHQ-12). Despite its canonical use as an outcome of interest in social science, the traditional use of the summed scores of summed questionnaires carries empirical and substantive assumptions which are often not fully considered or justified in the research. We outline the implications of these assumptions and the restrictions imposed by traditional modelling techniques and advocate for a more nuanced approach to population mental health inference. We use novel Exploratory Structural Equation Modelling (ESEM) on a large, representative UK sample taken from the first wave of the Understanding Society Survey, totalling 40,452 respondents. We use this to exemplify the potential of traditional, restrictive assumptions to bias conclusions and policy recommendations. ESEM analysis identifies a 4-factor structure for the GHQ-12, including a newly proposed “Emotional Coping” dimension. This structure is then tested against leading proposed factor structures from the literature and is demonstrated to perform better across all metrics, under both Maximum Likelihood and Bayesian estimation. Moreover, the proposed factors are more substantively dissimilar than those retrieved from previous literature. The results highlight the inferential limitations of using simple summed scores for mental health measurement. Use of the highlighted methods in combination with population studies offers quantitative social scientists the opportunity to explore predictors and patterns of underlying processes of population mental health outcomes, explicitly addressing the complexity and measurement error inherent to mental health analysis.
Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex
Authors: Werling Donna M. , Pochareddy Sirisha , Choi Jinmyung , An Joon-Yong , Sheppard Brooke , Peng Minshi , Li Zhen , Dastmalchi Claudia , Santpere Gabriel , Sousa Andre M. M. , Tebbenkamp Andrew T. N. , Kaur Navjot , Gulden Forrest O. , Breen Michael S. , Liang Lindsay , Gilson Michael C. , Zhao Xuefang , Dong Shan , Klei Lambertus , Cicek A. Ercument , Buxbaum Joseph D. , Adle-Biassette Homa , Thomas Jean-Leon , Aldinger Kimberly A. , O’Day Diana R. , Glass Ian A. , Zaitlen Noah A. , Talkowski Michael E. , Roeder Kathryn , State Matthew W. , Devlin Bernie , Sanders Stephan J. , Sestan Nenad 
Published: March 2019

SummaryVariation in gene expression underlies neurotypical development, while genomic variants contribute to neuropsychiatric disorders. BrainVar is a unique resource of paired whole-genome sequencing and bulk-tissue RNA-sequencing from the human dorsolateral prefrontal cortex of 176 neurotypical individuals across prenatal and postnatal development, providing the opportunity to assay genomic and transcriptomic variation in tandem. Leveraging this resource, we identified rare premature stop codons with commensurate reduced and allele-specific expression of corresponding genes, and common variants that alter gene expression (expression quantitative trait loci, eQTLs). Categorizing eQTLs by prenatal and postnatal effect, genes affected by temporally-specific eQTLs, compared to constitutive eQTLs, are enriched for haploinsufficiency, protein-protein interactions, and neuropsychiatric disorder risk loci. Expression levels of over 12,000 genes rise or fall in a concerted late-fetal transition, with the transitional genes enriched for cell type specific genes and neuropsychiatric disorder loci, underscoring the importance of cataloguing developmental trajectories in understanding cortical physiology and pathology.HighlightsWhole-genome and RNA-sequencing across human prefrontal cortex development in BrainVarGene-specific developmental trajectories characterize the late-fetal transitionIdentification of constitutive, prenatal-specific, postnatal-specific, and rare eQTLsIntegrated analysis reveals genetic and developmental influences on CNS traits and disorders
Genomic data and multi-species demographic modelling uncover past hybridization between currently allopatric freshwater species
Authors: Mendes Sofia L. , Machado Miguel P. , Coelho Maria M. , Sousa Vitor C. 
Published: March 2019

AbstractEvidence for ancient interspecific gene flow through hybridization has been reported in many animal and plant taxa based on genetic markers. The study of genomic patterns of closely related species with allopatric distributions allow to assess the relative importance of vicariant isolating events and past gene flow. Here, we investigated the role of gene flow in the evolutionary history of four closely related freshwater fish species with currently allopatric distributions in western Iberian rivers -Squalius carolitertii, S. pyrenaicus, S. torgalensisandS. aradensis- using a population genomics dataset of 23 562 SNPs from 48 individuals, obtained through genotyping by sequencing (GBS). We uncovered a species tree with two well differentiated clades: (i)S. carolitertiiandS. pyrenaicus; and (ii)S. torgalensisandS. aradensis. By using D-statistics and demographic modelling based on the site frequency spectrum, comparing alternative demographic scenarios of hybrid origin, secondary contact and isolation, we found that theS. pyrenaicusNorth lineage is likely the result of an ancient hybridization event betweenS. carolitertii(contributing ~84%) andS. pyrenaicusSouth lineage (contributing ~16%), consistent with a hybrid speciation scenario. Furthermore, in the hybrid lineage we identify outlier loci potentially affected by selection favouring genes from each parental lineage at different genomic regions. Our results suggest that ancient hybridization can affect speciation and that freshwater fish species currently in allopatry are useful to study these processes.
The genome of the blind soil-dwelling and ancestrally wingless dipluranCampodea augens, a key reference hexapod for studying the emergence of insect innovations
Authors: Manni Mosè , Simao Felipe A. , Robertson Hugh M. , Gabaglio Marco A. , Waterhouse Robert M. , Misof Bernhard , Niehuis Oliver , Szucsich Nikolaus U. , Zdobnov Evgeny M. 
Published: March 2019

AbstractThe dipluran two-pronged bristletailCampodea augensis a blind ancestrally wingless hexapod with the remarkable capacity to regenerate lost body appendages such as its long antennae. As sister group to Insecta (sensu stricto), Diplura are key to understanding the early evolution of hexapods and the origin and evolution of insects. Here we report the 1.2-Gbp draft genome ofC. augensand results from comparative genomic analyses with other arthropods. InC. augenswe uncovered the largest chemosensory gene repertoire of ionotropic receptors in the animal kingdom, a massive expansion which might compensate for the loss of vision. We found a paucity of photoreceptor genes mirroring at the genomic level the secondary loss of an ancestral external photoreceptor organ. Expansions of detoxification and carbohydrate metabolism gene families might reflect adaptations for foraging behaviour, and duplicated apoptotic genes might underlie its high regenerative potential.TheC. augensgenome represents one of the key references for studying the emergence of genomic innovations in insects, the most diverse animal group, and opens up novel opportunities to study the under-explored biology of diplurans.
Effect of user adaptation on prosthetic finger control with an intuitive myoelectric decoder
Authors: Krasoulis Agamemnon , Vijayakumar Sethu , Nazarpour Kianoush 
Published: March 2019

ABSTRACTMachine learning-based myoelectric control is regarded as an intuitive paradigm, because of the mapping it creates between muscle co-activation patterns and prosthesis movements that aims to simulate the physiological pathways found in the human arm. Despite that, there has been evidence that closed-loop interaction with a classification-based interface results in user adaptation, which leads to performance improvement with experience. Recently, there has been a focus shift towards continuous prosthesis control, yet little is known about whether and how user adaptation affects myoelectric control performance in dexterous, intuitive tasks. We investigate the effect of short-term adaptation with independent finger position control by conducting real-time experiments with 10 able-bodied and two transradial amputee subjects. We demonstrate that despite using an intuitive decoder, experience leads to significant improvements in performance. We argue that this is due to the lack of an utterly natural control scheme, which is mainly caused by differences in the anatomy of human and artificial hands, movement intent decoding inaccuracies, and lack of proprioception. Finally, we extend previous work in classification-based and wrist continuous control by verifying that offline analyses cannot reliably predict real-time performance, thereby reiterating the importance of validating myoelectric control algorithms with real-time experiments.
Error, noise and bias in de novo transcriptome assemblies
Authors: Freedman Adam H. , Clamp Michele , Sackton Timothy B. 
Published: March 2019

ABSTRACTDe novo transcriptome assembly is a powerful tool, widely used over the last decade for making evolutionary inferences. However, it relies on two implicit assumptions: that the assembled transcriptome is an unbiased representation of the underlying expressed transcriptome, and that expression estimates from the assembly are good, if noisy approximations of the relative abundance of expressed transcripts. Using publicly available data for model organisms, we demonstrate that, across assembly algorithms and data sets, these assumptions are consistently violated. Bias exists at the nucleotide level, with genotyping error rates ranging from 30-83%. As a result, diversity is underestimated in transcriptome assemblies, with consistent under-estimation of heterozygosity in all but the most inbred samples. Even at the gene level, expression estimates show wide deviations from map-to-reference estimates, and positive bias at lower expression levels. Standard filtering of transcriptome assemblies improves the robustness of gene expression estimates but leads to the loss of a meaningful number of protein-coding genes, including many that are highly expressed. We demonstrate a computational method, length-rescaled CPM, to partly alleviate noise and bias in expression estimates. Researchers should consider ways to minimize the impact of bias in transcriptome assemblies.
The shift from life in water to life on land advantaged planning in visually-guided behavior
Authors: Mugan Ugurcan , MacIver Malcolm A. 
Published: March 2019

AbstractOther than formerly land-based mammals such as whales and dolphins that have returned to an aquatic existence, it is uncontroversial that land animals have developed more elaborated cognitive abilities than aquatic animals. Yet there is no apparenta-priorireason for this to be the case. A key cognitive faculty is the ability to plan. Here we provide evidence that in a dynamic visually-guided behavior of crucial evolutionary importance, prey evading a predator, planning provides a significant advantage over habit-based action selection, but only on land. This advantage is dependent on the massive increase in visual range and spatial complexity that greeted the first vertebrates to view the world above the waterline 380 million years ago. Our results have implications for understanding the evolutionary basis of the limited ability of animals, including humans, to think ahead to meet slowly looming and distant threats, toward a neuroscience of sustainability.
OMGS: Optical Map-based Genome Scaffolding
Authors: Pan Weihua , Jiang Tao , Lonardi Stefano 
Published: March 2019

AbstractDue to the current limitations of sequencing technologies,de novogenome assembly is typically carried out in two stages, namely contig (sequence) assembly and scaffolding. While scaffolding is computationally easier than sequence assembly, the scaffolding problem can be challenging due to the high repetitive content of eukaryotic genomes, possible mis-joins in assembled contigs and inaccuracies in the linkage information. Genome scaffolding tools either use paired-end/mate-pair/linked/Hi-C reads or genome-wide maps (optical, physical or genetic) as linkage information. Optical maps (in particular Bionano Genomics maps) have been extensively used in many recent large-scale genome assembly projects (e.g., goat, apple, barley, maize, quinoa, sea bass, among others). However, the most commonly used scaffolding tools have a serious limitation: they can only deal with one optical map at a time, forcing users to alternate or iterate over multiple maps. In this paper, we introduce a novel scaffolding algorithm called OMGS that for the first time can take advantages of multiple optical maps. OMGS solves several optimization problems to generate scaffolds with optimal contiguity and correctness. Extensive experimental results demonstrate that our tool outperforms existing methods when multiple optical maps are available, and produces comparable scaffolds using a single optical map. OMGS can be obtained fromhttps://github.com/ucrbioinfo/OMGS
TM3’seq: a tagmentation-mediated 3’ sequencing approach for improving scalability of RNA-seq experiments
Authors: Pallares Luisa F. , Picard Serge , Ayroles Julien F. 
Published: March 2019

AbstractRNA-seq has become the standard tool for collecting genome-wide expression data in diverse fields, from quantitative genetics and medical genomics to ecology and developmental biology. However, RNA-seq library preparation is still prohibitive for many laboratories. Recently, the field of single-cell transcriptomics has reduced costs and increased throughput by adopting early barcoding and pooling of individual samples —producing a single final library containing all samples. In contrast, RNA-seq protocols where each sample is processed individually are significantly more expensive and lower throughput than single-cell approaches. Yet, many projects depend on individual library generation to preserve important samples or for follow-up re-sequencing experiments. Improving on currently available RNA-seq methods we have developed TM3’seq, a 3’-enriched library preparation protocol that uses Tn5 transposase and preserves sample identity at each step. TM3’seq is designed for high-throughput processing of individual samples (96 samples in 6h, with only 3h hands-on time) at a fraction of the cost of commercial kits ($1.5 per sample). The protocol was tested in a range of human andDrosophila melanogasterRNA samples, recovering transcriptomes of the same quality and reliability than the commercial NEBNext®kit. We expect that the cost-and time-efficient features of TM3’seq make large-scale RNA-seq experiments more permissive for the entire scientific community.
Circular RNA profiling in the oocyte and cumulus cells reveals thatcircARMC4is essential for porcine oocyte maturation
Authors: Cao Zubing , Gao Di , Xu Tengteng , Zhang Ling , Tong Xu , Zhang Dandan , Wang Yiqing , Ning Wei , Qi Xin , Ma Yangyang , Ji Kaiyuan , Yu Tong , Li Yunsheng , Zhang Yunhai 
Published: March 2019

ABSTRACTThousands of circular RNAs (circRNAs) have been recently discovered in cumulus cells and oocytes from several species. However, the expression and function of circRNA during porcine oocyte meiotic maturation have been never examined. Here, we separately identified 7,067 and 637 circRNAs in both the cumulus cell and the oocyte via deep sequencing and bioinformatic analysis. Further analysis revealed that a faction of circRNAs is differentially expressed (DE) in a developmental stage-specific manner. The host genes of DE circRNAs are markedly enriched to multiple signaling pathways associated with cumulus cell function and oocyte maturation. Additionally, most DE circRNAs harbor several miRNA targets, suggesting that these DE circRNAs potentially act as miRNA sponge. Importantly, we found that maternalcircARMC4knockdown by siRNA microinjection caused a severely impaired chromosome alignment, and significantly inhibited first polar body extrusion and early embryo development. Taken together, these results demonstrate for the first time that circRNAs are abundantly and dynamically expressed in a developmental stage-specific manner in cumulus cells and oocytes, and maternally expressedcircARMC4is essential for porcine oocyte meiotic maturation and early embryo development.
Neurodegeneration caused by LRRK2-G2019S requires Rab10 in select dopaminergic neurons
Authors: Petridi Stavroula , Middleton C. Adam , Fellgett Alison , Covill Laura , Stewart Amy , Munns Jack , Kohrs Friederike Elisabeth , Hiesinger P. Robin , Wilson Laurence , Chawla Sangeeta , Elliott Christopher J. H. 
Published: March 2019

AbstractInherited mutations in the LRRK2 protein are the commonest known cause of Parkinson’s, but the molecular link from increased kinase activity to pathological neurodegeneration remains to be determined.In vitro(biochemical and cell culture) assays led to the hypothesis that several Rab GTPases might be LRRK2 substrates. Here we show that Rab10 potently modifiesLRRK2-G2019Smediated electrophysiological responses in anin vivoscreen, in which each Rab was overexpressed inDrosophiladopaminergic neurons. We therefore tested the effect ofRab10loss of function on threeLRRK2-G2019Sphenotypes (vision, movement and sleep) that rely on dopaminergic circuits in both flies and mammals. The knock-out of Rab10in vivofully rescues the reduced responses induced by dopaminergicLRRK2-G2019Sin visual and motor (reaching, proboscis extension) assays, but the sleep phenotype is unaffected. We show that Rab10 is expressed in dopaminergic (tyrosine hydroxylase positive) neurons controlling vision and proboscis movement, but undetectable in those controlling sleep, indicating that anatomical and physiological patterns of Rab10 are related. Our results support the idea that LRRK2 phosphorylates separate targets in distinct neurons and confirm that one degenerative pathway starts with Rab10. Although Rab3 is another putative substrate of LRRK2, it shows no synergy with G2019S and localises to a different subset of dopaminergic neurons from Rab10. We propose that variations inRabexpression may contribute to differences in the rate of neurodegeneration seen in different dopaminergic nuclei in Parkinson’s.Significance StatementA key question in Parkinson’s is why dopamine neurons die particularly fast in some parts of thesubstantia nigra. We focused on the commonest Parkinson’s-related mutation, LRRK2-G2019S.In vitroassays suggested that neurodegeneration may start by LRRK2-G2019S increasing phosphorylation of Rab10. We found Rab10 in fly dopamine neurons in visual and motor pathways, but not in the sleep system. Rab10 knock-out rescues G2019S-induced visual and movement degeneration, leaving sleep dysfunction unaffected. Thus, LRRK2 activates at least two pathways, one Rab10-dependent, leading to neurodegenerationin vivo. Rab3 is found in a different subset of dopaminergic neurons and shows no synergy withLRRK2-G2019S. We propose that variations inRabexpression contribute to differences in neurodegeneration seen in Parkinson’s.