bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quaddles: A multidimensional 3D object set with parametrically-controlled and customizable features
Authors: Watson Marcus. R. , Voloh Benjamin , Naghizadeh Milad , Womelsdorf Thilo 
Published: September 2017

AbstractMany studies of vision and cognition require novel three-dimensional object sets defined by a parametric feature space. Creating such sets and verifying that they are suitable for a given task, however, can be extremely time-consuming and effortful. Here we present a new set of multidimensional objects,Quaddles, designed for a study of feature-based learning and attention, but adaptable for many research purposes. Quaddles have features that are all equally-visible from any angle around the vertical axis, and which all have similar response biases on a feature detection task, thus removing one potential source of bias in object selection. They are available as two-dimensional images, rotating videos, and FBX object files suitable for use with any modern video game engine. We also provide examples and tutorials for modifying Quaddles or creating completely new object sets from scratch, hopefully greatly speeding up the development time of future novel object studies.Author’s noteThis work was supported by grant MOP 102482 from the Canadian Institutes of Health Research (TW) and by the Natural Sciences and Engineering Research Council of Canada Brain in Action CREATE-IRTG program (MRW, TW). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of this manuscript. Authors would like to thank Hongying Wang for technical support, and Isabel Gauthier for comments on a draft version of the manuscript.The study described herein was approved by the York University Office of Research Ethics (Certificate # 2016-214).A draft version of this manuscript is available online at BioRχiv:
Smart switching in feedforward control of grip force during manipulation of elastic objects
Authors: White Olivier , Karniel Amir , Leib Raz , Papaxanthis Charalambos , Barbiero Marie , Nisky ilana 
Published: September 2017

AbstractSwitching systems are common in artificial control systems. Here, we suggest that the brain adopts a switched feedforward control of grip forces during manipulation of objects. We measured how participants modulated grip force when interacting with soft and rigid virtual springs when stiffness varied nearly continuously between trials. We identified a sudden phase transition between two forms of feedforward control that differed in the timing of the synchronization between the anticipated load force and the applied grip force. The switch occurred several trials after a threshold stiffness level. These results suggest that in the control of grip force, the brain acts as a switching control system. This opens new research questions as to the nature of the discrete state variables that drive the switching.
Olfactory fear conditioning non-specifically enhances glomerular odor responses and increases representational overlap of learned and neutral odors
Authors: Ross Jordan M. , Fletcher Max L. 
Published: September 2017

SummaryAssociative fear learning produces fear toward the conditioned stimulus (CS) and often generalization, the expansion of fear from the CS to similar, unlearned stimuli. However, how fear learning affects early sensory processing of learned and unlearned stimuli in relation to behavioral fear responses to these stimuli remains unclear. We subjected mice to a classical olfactory fear conditioning paradigm and used awake,in vivocalcium imaging to quantify learning-induced changes in glomerular odor responses, which constitutes the first site of olfactory processing in the brain. The results demonstrate that olfactory fear learning non-specifically enhances glomerular odor representations in a learning-dependent manner and increases representational similarity between the CS and non-conditioned odors. This mechanism may prime the system towards generalization of learned fear. Additionally, CS-specific enhancements remain even when associative learning is blocked; suggesting two separate mechanisms lead to enhanced glomerular responses following odor-shock pairings.
Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect susceptibility to developmental polychlorinated biphenyl exposure in mice: Relevance to studies of human neurological disorders
Authors: Klinefelter Kelsey , Hooven Molly Kromme , Bates Chloe , Colter Breann T. , Dailey Alexandra , Infante Smitha Krishnan , Kania-Korwel Izabela , Lehmler Hans-Joachim , López-Juárez Alejandro , Ludwig Clare Pickering , Curran Christine Perdan 
Published: September 2017

AbstractPolychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with the discovery of new sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but there is some evidence that high PCB exposure in adults increases the risk of Parkinson’s disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect susceptibility to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction. High-affinityAhrbCyp1a2(-/-)mice were most susceptible compared with poor-affinityAhrdCyp1a2(-/-)and wild typeAhrbCyp1a2(+/+)mice. Our follow-up studies assessed biochemical, histological and gene expression changes to identify the brain regions and pathways affected. We also measured PCB and metabolite levels in multiple tissues to determine if genotype altered toxicokinetics. We found evidence of AHR-mediated immune suppression with reduced thymus and spleen weights and significantly reduced thyroxine at P14. In the brain, the greatest changes were seen in the cerebellum where a foliation defect was over-represented inCyp1a2(-/-)mice. In contrast, we found no difference in tyrosine hydroxylase immuno-staining in the striatum. Gene expression patterns varied across the three genotypes, but there was clear evidence of AHR activation. Distribution of parent PCB congeners also varied by genotype with strikingly high levels of PCB 77 in poor-affinityAhrdCyp1a2(-/-)whileAhrbCyp1a2(+/+)mice effectively sequestered coplanar PCBs in the liver. Together, our data suggest that the AHR pathway plays a role in developmental PCB neurotoxicity, but we found little evidence that developmental exposure is a risk factor for Parkinson’s disease.
A distributed algorithm to maintain and repair the trail networks of arboreal ants
Authors: Chandrasekhar Arjun , Gordon Deborah M. , Navlakha Saket 
Published: September 2017

AbstractWe study how the arboreal turtle ant (Cephalotes goniodontus) solves a fundamental computing problem: maintaining a trail network and finding alternative paths to route around broken links in the network. Turtle ants form a routing backbone of foraging trails linking several nests and temporary food sources. This species travels only in the trees, so their foraging trails are constrained to lie on a natural graph formed by overlapping branches and vines in the tangled canopy. Links between branches, however, can be ephemeral, easily destroyed by wind, rain, or animal movements. Here we report a biologically feasible distributed algorithm, parameterized using field data, that can plausibly describe how turtle ants maintain the routing backbone and find alternative paths to circumvent broken links in the backbone. We validate the ability of this probabilistic algorithm to circumvent simulated breaks in synthetic and real-world networks, and we derive an analytic explanation for why certain features are crucial to improve the algorithm’s success. Our proposed algorithm uses fewer computational resources than common distributed graph search algorithms, and thus may be useful in other domains, such as for swarm computing or for coordinating molecular robots.
Fast and Accurate Genomic Analyses using Genome Graphs
Authors: Rakocevic Goran , Semenyuk Vladimir , Spencer James , Browning John , Johnson Ivan , Arsenijevic Vladan , Nadj Jelena , Ghose Kaushik , Suciu Maria C. , Ji Sun-Gou , Demir Gülfem , Li Lizao , Toptaş Berke Ç. , Dolgoborodov Alexey , Pollex Björn , Spulber Iosif , Glotova Irina , Kómár Péter , Stachyra Andrew , Li Yilong , Popovic Milos , Lee Wan-Ping , Källberg Morten , Jain Amit , Kural Deniz 
Published: September 2017

AbstractThe human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, which impairs read alignment and downstream analysis accuracy. Reference genome structures incorporating known genetic variation have been shown to improve the accuracy of genomic analyses, but have so far remained computationally prohibitive for routine large-scale use. Here we present a graph genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4.0 million indels. Our Graph Genome Pipeline requires 6.5 hours to process a 30x coverage WGS sample on a system with 36 CPU cores compared with 11 hours required by the GATK Best Practices pipeline. Using complementary benchmarking experiments based on real and simulated data, we show that using a graph genome reference improves read mapping sensitivity and produces a 0.5% increase in variant calling recall, or about 20,000 additional variants being detected per sample, while variant calling specificity is unaffected. Structural variations (SVs) incorporated into a graph genome can be genotyped accurately under a unified framework. Finally, we show that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. Our implementation is a significant advance towards fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses.
MatClassRSA: A Matlab toolbox for M/EEG classification and visualization of proximity matrices
Authors: Wang Bernard C. , Norcia Anthony M. , Kaneshiro Blair 
Published: September 2017

AbstractMatClassRSA is a Matlab toolbox that performs M/EEG classification and produces various visualizations of the resulting confusion matrices. This toolbox is aimed toward cognitive neuroscience researchers who wish to apply classification-style analyses to repeated trials of data. The functionalities of the toolbox fall into three categories: (1) M/EEG classification, (2) computation of Representational Dissimilarity Matrices (RDMs) from confusion or other proximity matrices, and (3) clustering and tree visualizations of RDMs. MatClassRSA combines out-of-the-box functionality with a variety of customization options. Usage of the toolbox requires only a high-level understanding of machine learning and the ability to call Matlab functions from scripts.
The Wild-type and Gain-of-function Mutant p53 Enhance p300 Autoacetylation through Conformational Switching
Authors: Kaypee Stephanie , Ghosh Raka , Sahadevan Smitha Asoka , Patil Shilpa , Shasmal Manidip , Ghosh Piya , Roy Neeladri , Sengupta Jayati , Roy Siddhartha , Kundu Tapas K. 
Published: September 2017

ABSTRACTThe transcriptional coactivator p300 is essential for p53 transactivation, although its precise mechanism remains unclear. We report that, p53 allosterically activates the acetyltransferase activity of p300 through the enhancement of p300 autoacetylation. Cryo-electron microscopy revealed that the domain organization of p300 is substantially altered upon binding of p53, suggesting that a structural switch may underpin the activation. Acetylated p300 accumulates near the transcription start sites accompanied by a similar enrichment of activating histone marks near those sites. Disruption of p53-p300 interaction by a site-directed peptide inhibitor abolished autoacetylated p300-mediated enhanced histone acetylation, suggesting a crucial role played by the allosteric activation in p53-mediated gene regulation. Gain-of-function mutant p53, known to impart aggressive proliferative properties in tumor cells, also activate p300 autoacetylation. The same peptide abolished many of the gain-of-functions of mutant p53 as well. We conclude that allosteric activation of p300 by p53 underpins gene regulation by p53. Reversal of gain-of-function properties of mutant p53 suggests that molecules targeting the p53-p300 interface may be good candidates for anti-tumor drugs.
Approximate Bayesian computation reveals the importance of repeated measurements for parameterising cell-based models of growing tissues
Authors: Kursawe Jochen , Baker Ruth E. , Fletcher Alexander G. 
Published: September 2017

AbstractThe growth and dynamics of epithelial tissues govern many morphogenetic processes in embryonic development. A recent quantitative transition in data acquisition, facilitated by advances in genetic and live-imaging techniques, is paving the way for new insights to these processes. Computational models can help us understand and interpret observations, and then make predictions for future experiments that can distinguish between hypothesised mechanisms. Increasingly, cell-based modelling approaches such as vertex models are being used to help understand the mechanics underlying epithelial morphogenesis. These models typically seek to reproduce qualitative phenomena, such as cell sorting or tissue buckling. However, it remains unclear to what extent quantitative data can be used to constrain these models so that they can then be used to make quantitative, experimentally testable predictions. To address this issue, we perform anin silicostudy to investigate whether vertex model parameters can be inferred from imaging data, and explore methods to quantify the uncertainty of such estimates. Our approach requires the use of summary statistics to estimate parameters. Here, we focus on summary statistics of cellular packing and of laser ablation experiments, as are commonly reported from imaging studies. We find that including data from repeated experiments is necessary to generate reliable parameter estimates that can facilitate quantitative model predictions.
Genomic signature of experimental adaptation ofStaphylococcus aureusto a natural combination of insect antimicrobial peptides
Authors: Makarova Olga , Johnston Paul , Rodriguez-Rojas Alexandro , el-Shazely Baydaa , Moreno Morales Javier , Rolff Jens 
Published: September 2017

AbstractAntimicrobial peptides are highly conserved immune effectors across the tree of life and are employed as combinations. In the beetleTenebrio molitor, a defensin and a coleoptericin are highly expressedin vivoafter inoculation withS. aureus. The defensin displays strongin vitroactivity but no survival benefitin vivo. The coleoptericin provides a survival benefit in vivo, but no activity in vitro. To investigate this paradox we experimentally evolvedS. aureusto increased resistance against the defensin and a combination of the defensin and coleoptericin. Genome re-sequencing showed that resistance was associated with mutations in either theytrornsaoperons, in both AMP treatments. Strains with these mutations show longer lag phases, slower Vmax andnsamutants reach lower final population sizes. Mutations inrpoBwere showed a further increase in the lag phase innsamutants but not inytrmutants. In contrast, final MICs do not segregate by mutation. All resistant lines display AMP but not antibiotic cross-resistance. Costly resistance against AMPs readily evolves for an individual AMP as well as a naturally occurring combinationin vitroand provides broad protection against AMPs. Such non-specific resistance could result in strong selection on host immune systems that rely on cocktails of AMPs.
Uncoordinated centrosome duplication cycle underlies the instability of non-diploid states in mammalian somatic cells
Authors: Yaguchi Kan , Matsui Ryo , Yamamoto Takahiro , Tsukada Yuki , Shibanuma Atsuko , Kamimura Keiko , Koda Toshiaki , Uehara Ryota 
Published: September 2017

AbstractIn animals, somatic cells are usually diploid and are unstable when haploid for unknown reasons. In this study, by comparing isogenic human cell lines with different ploidies, we found frequent centrosome loss specifically in the haploid state, which profoundly contributed to haploid instability through monopolar spindle formation and subsequent mitotic defects. We also found that efficiency of centriole licensing and duplication, but not that of DNA replication, changes proportionally to ploidy level, causing gradual loss or frequent overduplication of centrioles in haploid and tetraploid cells, respectively. Centriole licensing efficiency seemed to be modulated by astral microtubules, whose development scaled with ploidy level, and artificial enhancement of aster formation in haploid cells restored centriole licensing efficiency to diploid levels. Haploid-specific centrosome loss was also observed in parthenogenetic mouse embryos. We propose that incompatibility between the centrosome duplication and DNA replication cycles arising from different scaling properties of these bioprocesses upon ploidy changes, underlies the instability of non-diploid somatic cells in mammals.SummaryYaguchi et al. show that a delay or acceleration of centriole licensing compromises the control of centrosome number in haploid or tetraploid human cells, respectively, suggesting a cellular basis of the instability of non-diploid somatic cells in mammals.
Individual nephron proteomes connect morphology and function in proteinuric kidney disease
Authors: Höhne Martin , Frese Christian K. , Grahammer Florian , Dafinger Claudia , Ciarimboli Giuliano , Butt Linus , Binz Julia , Hackl Matthias J. , Rahmatollahi Mahdieh , Kann Martin , Schneider Simon , Altintas Mehmet M. , Schermer Bernhard , Reinheckel Thomas , Göbel Heike , Reiser Jochen , Huber Tobias B. , Kramann Rafael , Seeger-Nukpezah Tamina , Liebau Max C. , Beck Bodo B. , Benzing Thomas , Beyer Andreas , Rinschen Markus M. 
Published: September 2017

AbstractIn diseases of many parenchymatous organs, heterogenous detoriation of individual functional units determines the clinical prognosis. However, the molecular characterization of these subunits remains a technological challenge that needs to be addressed in order to better understand pathological mechanisms. Sclerotic and proteinuric glomerular kidney disease is a frequent and heterogeneous disease which affects a fraction of nephrons, glomeruli and draining tubules, to variable extents, and for which no treatment exists. Here, we developed and applied an antibody-independent methodology to investigate heterogeneity of individual nephron segment proteomes from mice with proteinuric kidney disease. This “one-segment-one-proteome-approach” defines mechanistic connections between upstream (glomerular) and downstream (tubular) nephron segment populations. In single glomeruli from two different mouse models of sclerotic glomerular disease, we identified a coherent protein expression module consisting of extracellular matrix protein deposition (reflecting glomerular sclerosis), glomerular albumin (reflecting proteinuria) and LAMP1, a lysosomal protein. This module was associated with a loss of podocyte marker proteins. In an attempt to target this protein co-expression module, genetic ablation of LAMP1-correlated lysosomal proteases in mice could ameliorate glomerular damage. Furthermore, individual glomeruli from patients with genetic sclerotic and non-sclerotic proteinuric diseases demonstrated increased abundance of lysosomal proteins, in combination with a decreased abundance of the mutated gene products. Therefore, increased glomerular lysosomal load is a conserved key mechanism in proteinuric kidney diseases, and the technology applied here can be implemented to address heterogeneous pathophysiology in a variety of diseases at a sub-biopsy scale
Neural coding of fine-grained object knowledge in perirhinal cortex
Authors: Price Amy Rose , Bonner Michael F. , Peelle Jonathan E. , Grossman Murray 
Published: September 2017

SummaryOver 40 years of research has examined the role of the ventral visual stream in transforming retinal inputs into high-level representations of object identity [1–6]. However, there remains an ongoing debate over the role of the ventral stream in coding abstract semantic content, which relies on stored knowledge, versus perceptual content that relies only on retinal inputs [7–12]. A major difficulty in adjudicating between these mechanisms is that the semantic similarity of objects is often highly confounded with their perceptual similarity (e.g., animate things are more perceptually similar to other animate things than to inanimate things). To address this problem, we developed a paradigm that exploits the statistical regularities of object colors while perfectly controlling for perceptual shape information, allowing us to dissociate lower-level perceptual features (i.e., color perception) from higher-level semantic knowledge (i.e., color meaning). Using multivoxel-pattern analyses of fMRI data, we observed a striking double dissociation between the processing of color information at a perceptual and at a semantic level along the posterior to anterior axis of the ventral visual pathway. Specifically, we found that the visual association region V4 assigned similar representations to objects with similar colors, regardless of object category. In contrast, perirhinal cortex, at the apex of the ventral visual stream, assigned similar representations to semantically similar objects, even when this was in opposition to their perceptual similarity. These findings suggest that perirhinal cortex untangles the representational space of lower-level perceptual features and organizes visual objects according to their semantic interpretations.
A system-wide approach to monitor responses to synergistic BRAF and EGFR inhibition in colorectal cancer cells
Authors: Ressa Anna , Bosdriesz Evert , de Ligt Joep , Mainardi Sara , Maddalo Gianluca , Prahallad Anirudh , Jager Myrthe , de la Fonteijne Lisanne , Fitzpatrick Martin , Groten Stijn , Altelaar A. F. Maarten , Bernards René , Cuppen Edwin , Wessels Lodewyk , Heck Albert J. R. 
Published: September 2017

AbstractIntrinsic and/or acquired resistance represents one of the great challenges in targeted cancer therapy. A deeper understanding of the molecular biology of cancer has resulted in more efficient strategies, where one or multiple drugs are adopted in novel therapies to tackle resistance. This beneficial effect of using combination treatments has also been observed in colorectal cancer patients harboring the BRAF(V600E) mutation, whereby dual inhibition of BRAF(V600E) and EGFR increases antitumor activity. Notwithstanding this success, it is not clear whether this combination treatment is the only or most effective treatment to block intrinsic resistance to BRAF inhibitors. Here, we investigate molecular responses upon single and multi-target treatments, over time, using BRAF(V600E) mutant colorectal cancer cells as a model system. Through integration of transcriptomic, proteomic and phosphoproteomics data we obtain a comprehensive overview, revealing both known and novel responses. We primarily observe widespread upregulation of receptors tyrosine kinases and metabolic pathways upon BRAF inhibition. These findings point to mechanisms by which the drug-treated cells switch energy sources and enter a quiescent-like state as a defensive response, while additionally reactivating the MAPK pathway.