bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila larval brain neoplasms present tumour-type dependent genome instability
Authors: Rossi Fabrizio , Stephan-Otto Attolini Camille , Mosquera Jose Luis , Gonzalez Cayetano 
Published: September 2017

ABSTRACTSingle nucleotide polymorphisms (SNPs) and copy number variants (CNVs) are found at different rates in human cancer. To determine if these genetic lesions appear in Drosophila tumours we have sequenced the genomes of 17 malignant neoplasms caused by mutationsin l(3)mbt, brat, aurA, orlgl. We have found CNVs and SNPs in all the tumours. Tumour-linked CNVs range between 11 and 80 per sample, affecting between 92 and 1546 coding sequences. CNVs are in average less frequent inl(3)mbtthan inbratlines. Nearly half of the CNVs fall within the 10 to 100Kb range, all tumour samples contain CNVs larger that 100 Kb and some have CNVs larger than 1Mb. The rates of tumour-linked SNPs change more than 20-fold depending on the tumour type: late stagebrat,l(3)mbt, andaurAand lgl lines present median values of SNPs/Mb of exome of 0.16, 0.48, and 3.6, respectively. Higher SNP rates are mostly accounted for by C>A transversions, which likely reflect enhanced oxidative stress conditions in the affected tumours. Both CNVs and SNPs turn over rapidly. We found no evidence for selection of a gene signature affected by CNVs or SNPs in the cohort. Altogether, our results show that the rates of CNVs and SNPs, as well as the distribution of CNV sizes in this cohort of Drosophila tumours are well within the range of those reported for human cancer. Genome instability is therefore inherent to Drosophila malignant neoplastic growth at a variable extent that is tumour type dependent.AUTHOR SUMMARYDrosophila models of malignant growth can help to understand the molecular mechanisms of malignancy. These models are known to exhibit some of the hallmarks of cancer like sustained growth, immortality, metabolic reprogramming, and others. However, it is currently unclear if these fly models are affected by genome instability, which is another hallmark of many human malignant tumours. To address this issue we have sequenced and analysed the genomes of a cohort of seventeen fly tumour samples. We have found that genome instability is a common trait of Drosophila malignant tumours, which occurs at an extent that is tumour-type dependent, at rates that are similar to those of different human cancers.
Molecular basis for the maintenance of lipid asymmetry in the outer membrane ofEscherichia coli
Authors: Yeow Jiang , Tan Kang Wei , Holdbrook Daniel A. , Chong Zhi-Soon , Marzinek Jan K. , Bond Peter J. , Chng Shu-Sin 
Published: September 2017

AbstractA distinctive feature of the Gram-negative bacterial cell envelope is the asymmetric outer membrane (OM), where lipopolysaccharides (LPS) and phospholipids (PLs) reside in the outer and inner leaflets, respectively. This unique lipid asymmetry renders the OM impermeable to external insults. InEscherichia coli, the OmpC-MlaA complex is believed to maintain lipid asymmetry by removing mislocalized PLs from the outer leaflet of the OM. How it performs this function is unknown. Here, we define the molecular architecture of the OmpC-MlaA complex to gain insights into its role in PL transport. We establish that MlaA sits entirely within the bilayer in complex with OmpC and provides a hydrophilic channel possibly for PL translocation across the OM. Furthermore, we show that flexibility in a hairpin loop adjacent to the channel modulates MlaA activity. Finally, we demonstrate that OmpC plays an active role in maintaining OM lipid asymmetry together with MlaA. Our work offers glimpses into how the OmpC-MlaA complex transports PLs across the OM and has important implications for future antimicrobial drug development.
Deep transfer learning-based hologram classification for molecular diagnostics
Authors: Kim Sung-Jin , Wang Chuangqi , Zhao Bing , Im Hyungsoon , Min Jouha , Choi Hee June , Tadros Joseph , Choi Nu Ri , Castro Cesar M. , Weissleder Ralph , Lee Hakho , Lee Kwonmoo 
Published: September 2017

ABSTRACTLens-free digital in-line holography (LDIH) is a promising microscopic tool that overcomes several drawbacks (e.g., limited field of view) of traditional lens-based microcopy. However, extensive computation is required to reconstruct object images from the complex diffraction patterns produced by LDIH, which limits LDIH utility for point-of-care applications, particularly in resource limited settings. Here, we describe a deep transfer learning (DTL) based approach to process LDIH images in the context of cellular analyses. Specifically, we captured holograms of cells labeled with molecular-specific microbeads and trained neural networks to classify these holograms without reconstruction. Using raw holograms as input, the trained networks were able to classify individual cells according to the number of cell-bound microbeads. The DTL-based approach including a VGG19 pretrained network showed robust performance with experimental data. Combined with the developed DTL approach, LDIH could be realized as a low-cost, portable tool for point-of-care diagnostics.
The Asian tiger mosquito,Aedes albopictus(Skuse, 1894), a vector of dengue, chikungunya and zika, reaches Portugal
Authors: Marabuto Eduardo , Rebelo Maria Teresa 
Published: September 2017

AbstractThe mosquitoAedes albopictusis here reported for the first time in Portugal, from the south of the country, at least 240km west of the nearest known observation in Spain. A population of more than fifty specimens was spotted within a suburban garden over seven days of survey. As an important vector of Human affecting zoonoses such as dengue, chikungunya and yellow-fever, the presence of this mosquito in Portugal now enhances the outbreak chances for such diseases.
A model species for agricultural pest genomics: the genome of the Colorado potato beetle,Leptinotarsa decemlineata(Coleoptera: Chrysomelidae)
Authors: Schoville Sean D. , Chen Yolanda H. , Andersson Martin N. , Benoit Joshua B. , Bhandari Anita , Bowsher Julia H. , Brevik Kristian , Cappelle Kaat , Chen Mei-Ju M. , Childers Anna K. , Childers Christopher , Christiaens Olivier , Clements Justin , Didion Elise M. , Elpidina Elena N. , Engsontia Patamarerk , Friedrich Markus , García-Robles Inmaculada , Gibbs Richard A. , Goswami Chandan , Grapputo Alessandro , Gruden Kristina , Grynberg Marcin , Henrissat Bernard , Jennings Emily C. , Jones Jeffery W. , Kalsi Megha , Khan Sher A. , Kumar Abhishek , Li Fei , Lombard Vincent , Ma Xingzhou , Martynov Alexander , Miller Nicholas J. , Mitchell Robert F. , Munoz-Torres Monica , Muszewska Anna , Oppert Brenda , Palli Subba Reddy , Panfilio Kristen A. , Pauchet Yannick , Perkin Lindsey C. , Petek Marko , Poelchau Monica F. , Record Éric , Rinehart Joseph P. , Robertson Hugh M. , Rosendale Andrew J. , Ruiz-Arroyo Victor M. , Smagghe Guy , Szendrei Zsofia , Thomas Gregg W. C. , Torson Alex S. , Vargas Jentzsch Iris M. , Weirauch Matthew T. , Yates Ashley D. , Yocum George D. , Yoon June-Sun , Richards Stephen 
Published: September 2017

AbstractThe Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain whyLeptinotarsa decemlineatahas high sensitivity to dsRNA. TheL. decemlineatagenome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.
A high throughput screen for active human transposable elements
Authors: Kvikstad Erika M. , Piazza Paolo , Taylor Jenny C. , Lunter Gerton 
Published: September 2017

ABSTRACTTransposable elements (TEs) are mobile genetic sequences that randomly propagate within their host’s genome. This mobility has the potential to affect gene transcription and cause disease. However, TEs are technically challenging to identify, which complicates efforts to assess the impact of TE insertions on disease. Here we present a targeted sequencing protocol and computational pipeline to identify polymorphic and novel TE insertions using next-generation sequencing: TE-NGS. The method simultaneously targets the three subfamilies that are responsible for the majority of recent TE activity (L1HS,AluYa5/8, andAluYb8/9) thereby obviating the need for multiple experiments and reducing the amount of input material required. Here we describe the laboratory protocol and detection algorithm, and a benchmark experiment for the reference genome NA12878. We demonstrate a substantial enrichment for on-target fragments, and high sensitivity and precision to both reference and NA12878-specific insertions. We report 17 previously unreported loci for this individual which are supported by orthogonal long-read evidence, and we identify 1,471 polymorphic and novel TEs in 12 additional samples that were previously undocumented in databases of insertion polymorphisms. We anticipate that future applications of TE-NGS alongside exome sequencing of patients with sporadic disease will reduce the number of unresolved cases, and improve estimates of the contribution of TEs to human genetic disease.
Paternal-age-related de novo mutations and risk for five disorders
Authors: Taylor Jacob L. , Debost Jean-Christophe P.G. , Morton Sarah U. , Wigdor Emilie M. , Heyne Henrike O. , Lal Dennis , Howrigan Daniel P. , Bloemendal Alex , Larsen Janne T. , Kosmicki Jack A. , Weiner Daniel J. ,   Pediatric Cardiac Genomics Consortium, Homsy Jason , Seidman Jonathan G. , Seidman Christine E. , Agerbo Esben , McGrath John J. , Mortensen Preben Bo , Petersen Liselotte , Daly Mark J. , Robinson Elise B. 
Published: September 2017

AbstractBackgroundThere are well-established epidemiologic associations between advanced paternal age and increased offspring risk for several psychiatric and developmental disorders. These associations are commonly attributed to age-relatedde novomutations. However, the actual magnitude of risk conferred by age-relatedde novomutations in the male germline is unknown. Quantifying this risk would clarify the clinical and public health significance of delayed paternity.MethodsUsing results from large, parent-child trio whole-exome-sequencing studies, we estimated the relationship between paternal-age-relatedde novosingle nucleotide variants (dnSNVs) and offspring risk for five disorders: autism spectrum disorders (ASD), congenital heart disease (CHD), neurodevelopmental disorders with epilepsy (EPI), intellectual disability (ID), and schizophrenia (SCZ). Using Danish national registry data, we then investigated the degree to which the epidemiologic association between each disorder and advanced paternal age was consistent with the estimated role ofde novomutations.ResultsIncidence rate ratios comparing dnSNV-based risk to offspring of 45 versus 25-year-old fathers ranged from 1.05 (95% confidence interval 1.01–1.13) for SCZ to 1.29 (95% CI 1.13-1.68) for ID. Epidemiologic estimates of paternal age risk for CHD, ID and EPI were consistent with the dnSNV effect. However, epidemiologic effects for ASDs and SCZ significantly exceeded the risk that could be explained by dnSNVs alone (p<2e-4 for both comparisons).ConclusionIncreasing dnSNVs due to advanced paternal age confer a small amount of offspring risk for psychiatric and developmental disorders. For ASD and SCZ, epidemiologic associations with delayed paternity largely reflect factors that cannot be assumed to increase with age.
Eco-evolutionary dynamics and collective dispersal: implications for salmon metapopulation robustness
Authors: Yeakel Justin D. , Gibert Jean P. , Westley Peter A. H. , Moore Jonathan W. 
Published: September 2017

The spatial dispersal of individuals is known to play an important role in the dynamics of populations, and is central to metapopulation theory. At the same time, local adaptation to environmental conditions creates a geographic mosaic of evolutionary forces, where the combined drivers of selection and gene flow interact. Although the dispersal of individuals from donor to recipient populations provides connections within the metapopulation, promoting demographic and evolutionary rescue, it may also introduce maladapted individuals into habitats host to different environmental conditions, potentially lowering the fitness of the recipient population. Thus, dispersal plays a dual role in both promoting and inhibiting local adaptation. Here we explore a model of the eco-evolutionary dynamics between two populations connected by dispersal, where the productivity of each is defined by a trait complex that is subject to local selection. Although general in nature, our model is inspired by salmon metapopulations, where dispersal between populations is defined in terms of the straying rate, which has been shown to be density-dependent, and recently proposed to be shaped by social interactions consistent with collective movement. The results of our model reveal that increased straying between evolving populations leads to alternative stable states, which has large and nonlinear effects on two measures of metapopulation robustness: the portfolio effect and the time to recovery following an induced disturbance. We show that intermediate levels of straying result in large gains in robustness, and that increased habitat heterogeneity promotes robustness when straying rates are low, and erodes robustness when straying rates are high. Finally, we show that density-dependent straying promotes robustness, particularly when the aggregate biomass is low and straying is correspondingly high, which has important ramifications for the conservation of salmon metapopulations facing both natural and anthropogenic disturbances.Media SummaryMany migratory species, such as salmon, are remarkable in finding their way home. This homing has allowed fine-scale adaptations to the environments in which they evolve. But some individuals do not find their way home and instead stray to other locations, especially when there are fewer individuals to help with collective decision-making. With an eco-evolutionary model, we discovered that an intermediate and density-dependent straying rate allows linked populations to be robust to disturbance but maintain local adaptations.
Done in 100 ms: Path-dependent visuomotor transformation in the human upper limb
Authors: Gu Chao , Andrew Pruszynski J. , Gribble Paul L. , Corneil Brian D. 
Published: September 2017

ABSTRACTA core assumption underlying mental chronometry is that more complex tasks increase cortical processing, prolonging reaction times. Here we show that increases in task complexity alter the magnitude, rather than the latency, of the output for a circuit that rapidly transforms visual information into motor actions. We quantified visualstimulus-locked responses(SLRs), which are changes in upper limb muscle recruitment that evolve at a fixed latency ∼100 ms after novel visual stimulus onset. First, we studied the underlying reference frame of the SLR, by dissociating initial eye and hand position. Despite its quick latency, we found that the SLR was expressed in a hand-centric reference frame, suggesting that the circuit mediating the SLR integrated retinotopic visual information with body configuration. Next, we studied the influence of planned movement trajectory, requiring participants to prepare and generate curved or straight reaches in the presence of obstacles to attain the same visual stimulus. We found that SLR magnitude reflected the initial planned movement trajectory, regardless of the ensuing movement curvature. Based on these results, we suggest that the circuit mediating the SLR lies in parallel to other well-studied corticospinal pathways. Although the fixed latency of the SLR precludes extensive cortical processing, inputs conveying information relating to task complexity, such as body configuration and planned movement trajectory, can pre-set nodes within the circuit underlying to the SLR to modulate its magnitude.SIGNIFICANCE STATEMENTA core assumption underlying mental chronometry is that more complex tasks increase cortical processing, prolonging reaction times. Here, we showed that increases in task complexity altered the magnitude, rather than the latency, of a circuit that rapidly transforms visual information into motor actions. We focus onstimulus-locked responses(SLRs), which are changes in upper limb muscle recruitment that evolve at a fixed latency ∼100 ms after novel visual stimulus onset. We showed that despite is quick latency, the circuitry mediating the SLR transformed a retinotopic visual signal into a hand-centric motor command suitable to contribute to the initial movement trajectory. We suggest that this circuit lies in parallel to other well-studied corticospinal pathways.
UniProt Genomic Mapping for Deciphering Functional Effects of Missense Variants
Authors: McGarvey Peter B. , Nightingale Andrew , Luo Jie , Huang Hongzhan , Martin Maria J. , Wu Cathy ,   the UniProt Consortium
Published: September 2017

AbstractUnderstanding the association of genetic variation with its functional consequences in proteins is essential for the interpretation of genomic data and identifying causal variants in diseases. Integration of protein function knowledge with genome annotation can assist in rapidly comprehending genetic variation within complex biological processes. Here, we describe mapping UniProtKB human sequences and positional annotations such as active sites, binding sites, and variants to the human genome (GRCh38) and the release of a public genome track hub for genome browsers. To demonstrate the power of combining protein annotations with genome annotations for functional interpretation of variants, we present specific biological examples in disease-related genes and proteins. Computational comparisons of UniProtKB annotations and protein variants with ClinVar clinically annotated SNP data show that 32% of UniProtKB variants co-locate with 8% of ClinVar SNPs. The majority of co-located UniProtKB disease-associated variants (86%) map to ‘pathogenic’ ClinVar SNPs. UniProt and ClinVar are collaborating to provide a unified clinical variant annotation for genomic, protein and clinical researchers. The genome track hubs, and related UniProtKB files, are downloadable from the UniProt FTP site and discoverable as public track hubs at the UCSC and Ensembl genome browsers.
Chromatin accessibility profiling uncovers genetic- and T2D disease state-associated changes incis-regulatory element use in human islets
Authors: Khetan Shubham , Kursawe Romy , Youn Ahrim , Lawlor Nathan , Campos Eladio Marquez , Ucar Duygu , Stitzel Michael L. 
Published: September 2017

AbstractGenetic and environmental factors both contribute to islet dysfunction and failure, resulting in type 2 diabetes (T2D). The islet epigenome integrates these cues and can be remodeled by genetic and environmental variation. However, our knowledge of how genetic variants and T2D disease state alter human islet chromatin landscape andcis-regulatory element (RE) use is lacking. To fill this gap, we profiled and analyzed human islet chromatin accessibility maps from 19 genotyped individuals (5 with T2D) using ATAC-seq technology. Chromatin accessibility quantitative trait locus (caQTL) analyses identified 3001 sequence variants (FDR<10%) altering putativecis-RE use/activity. Islet caQTL were significantly and specifically enriched in islet stretch enhancers and islet-specific transcription factor binding motifs, such as FOXA2, NKX6.1, RFX5/6 and PDX1. Importantly, these analyses identified putative functional single nucleotide variants (SNVs) in 13 T2D-associated GWAS loci, including those previously associated with alteredZMIZ1, MTNR1B, RNF6,andADCY5islet expression, and linked the risk alleles to increased (n=8) or decreased (n=5) islet chromatin accessibility. Luciferase reporter assays confirmed allelic differences incis-RE activity for 5/9 caQTL sequences tested, including a T2D-associated SNV in theIL20RAlocus. Comparison of T2D and non-diabetic islets revealed 1882 open chromatin sites exhibiting T2D-associated chromatin accessibility changes (FDR<10%). Together, this study provides new insights into genetic variant and T2D disease state effects on isletcis-RE use and serves as an important resource to identify putative functional variants in T2D-and islet dysfunction-associated GWAS loci and link their risk allele toin vivoloss or gain of chromatin accessibility.
Metabolic scaling of individuals vs. populations: Evidence for variation in scaling exponents at different hierarchical levels
Authors: Norin Tommy , Gamperl A. Kurt 
Published: September 2017

Abstract

The power scaling of metabolic rate with body mass is fundamental to animal biology, due to the profound influence that animal size has on ecology and physiology. Yet the value of the scaling exponent (b) is highly debated. This scaling exponent has been suggested to be fixed at 0.67 or 0.75, or to vary systematically with cell size or metabolic intensity between the boundaries of 0.67 and 1. Despite this tremendous interest in the value of scaling exponents, little is known about metabolic scaling within individual animals and how this relates to population‐level scaling.

Here, we conducted a long‐term study that repeatedly characterised the complete metabolic profile of a group of 68 individual fish (cunner, Tautogolabrus adspersus) by measuring their standard metabolic rate (SMR), routine metabolic rate (RMR), active metabolic rate (AMR) and aerobic scope (AS) in five separate trials over 10 months (fish mass range, 0.5–19.5 g).

At all levels of metabolic intensity, the mean exponents for the group of fish at any single point in time (i.e. within trials; bSMR = 0.89, bRMR = 0.89, bAMR = 0.94, bAS = 0.96) were higher than those characterising the group as it aged (i.e. across trials; bSMR = 0.82, bRMR = 0.84, bAMR = 0.90, bAS = 0.92), and both were higher than the mean exponents for individual fish as they grew (i.e. across trials but within individuals; bSMR = 0.74, bRMR = 0.79, bAMR = 0.83, bAS = 0.85).

This variation in scaling relationships, which occurred at different hierarchical levels and across time as the fish aged, may have implications for bioenergetics and ecosystem modelling and for individual ecological and physiological studies where body mass adjustments are made using specific scaling exponents to compare traits of interest between different‐sized individuals.

The findings suggest that studies on fish population dynamics should apply metabolic scaling exponents that are significantly higher than those used in studies on individuals. However, the generality of this assertion should be confirmed by future work, as a few existing studies on endotherms (mainly birds) have reported shallower scaling relationships for basal metabolic rate between individuals as compared to within individuals.

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