bluuebunny/crossref_metadata_2025_split huggingface dataset:
An atlas of transcription factors expressed in theDrosophila melanogasterpupal terminalia
Authors: Vincent Ben J. , Rice Gavin R. , Wong Gabriella M. , Glassford William J. , Downs Kayla I. , Shastay Jessica L. , Charles-Obi Kenechukwu , Natarajan Malini , Gogol Madelaine , Zeitlinger Julia , Rebeiz Mark 
Published: June 2019

AbstractDuring development, transcription factors and signaling molecules govern gene regulatory networks to direct the formation of unique morphologies. As changes in gene regulatory networks are often implicated in morphological evolution, mapping transcription factor landscapes is important, especially in tissues that undergo rapid evolutionary change. The terminalia (genital and anal structures) ofDrosophila melanogasterand its close relatives exhibit dramatic changes in morphology between species. While previous studies have found network components important for patterning the larval genital disc, the networks governing adult structures during pupal development have remained uncharted. Here, we performed RNA-seq in wholeDrosophila melanogasterterminalia followed byin situhybridization for 100 highly expressed transcription factors during pupal development. We find that the terminalia is highly patterned during pupal stages and that specific transcription factors mark separate structures and substructures. Our results are housed online in a searchable database (flyterminalia.pitt.edu) where they can serve as a resource for the community. This work lays a foundation for future investigations into the gene regulatory networks governing the development and evolution ofDrosophilaterminalia.SummaryWe performed RNA-seq in wholeDrosophila melanogasterterminalia (genitalia and analia) followed byin situhybridization for 100 highly expressed transcription factors during pupal development. We find that the pupal terminalia is highly patterned with specific transcription factors marking separate structures and substructures. Our results are housed online in a searchable database (flyterminalia.pitt.edu) where they can serve as a resource for the community. This work lays a foundation for future investigations into the gene regulatory networks governing the development and evolution ofDrosophilaterminalia.
Reproducible Tract Profiles (RTP): from diffusion MRI acquisition to publication
Authors: Lerma-Usabiaga Garikoitz , Perry Michael L. , Wandell Brian A. 
Published: June 2019

AbstractReproducible Tract Profiles (RTP) comprises a set of methods to manage and analyze diffusion weighted imaging (DWI) data for reproducible tractography. The tools take MRI data from the scanner and process them through a series of analysis implemented as Docker containers that are integrated into a modern neuroinformatics platform (Flywheel). The platform guarantees that the entire pipeline can be re-executed, using the same data and computational parameters. In this paper, we describe (1) a cloud based neuroinformatics platform, (2) a tool to programmatically access and control the platform from a client, and (3) the DWI analysis tools that are used to identify the positions of 22 tracts and their diffusion profiles. The combination of these three components defines a system that transforms raw data into reproducible tract profiles for publication.Graphical abstractReproducible Tract Profiles (RTP) comprises a set of methods to manage and analyze diffusion weighted imaging (DWI) data for reproducible tractography. The RTP methods comprise two main parts.
Server side software tools for storing data and metadata and managing containerized computations.Client side software tools that enable the researcher to read data and metadata and manage server-side computations.The server-side computational tools are embedded in containers that are linked to a JSON file with a complete specification of the computational parameters. The data and computational infrastructure on the server is fully reproducible.
Movement behavioral plasticity of benthic diatoms driven by optimal foraging
Authors: Hu Wen-Si , Huang Mingji , Zhang H. P. , Zhang Feng , Vyverman Wim , Liu Quan-Xing 
Published: June 2019

ABSTRACTAdaptive locomotion of living organisms contributes to their competitive abilities and helps maintain their fitness in diverse environments. To date, however, our understanding of searching behavior and its ultimate cause remains poorly understood in ecology and biology. Here, we investigate motion patterns of biofilm-inhabiting marine raphid diatomNavicula arenariavar.rostellatain two-dimensional space. We report that individualNaviculacells display a “circular run-and-reversal” movement behavior at different concentrations of dissolved silicic acid (dSi). We show that gliding motions of cells can be predicted accurately with a universal Langevin model. Our experimental results are consistent with an optimal foraging strategy and a maximized diffusivity of the theoretical outcomes in which both circular-run and reversal behaviors are important ingredients. Our theoretical results suggest that the evolving movement behaviors of diatoms may be driven by optimization of searching behavioral strategy, and predicted behavioral parameters coincide with the experimental observations. These optimized movement behaviors are an evolutionarily stable strategy to cope with environmental complexity.ONE SENTENCE SUMMARYNovel experiments and modelling reveal that raphid diatoms can actively exploit resources in complex environments by adjusting their movement behavior.
A computational mechanism for seeing dynamic deformation
Authors: Kawabe Takahiro , Sawayama Masataka 
Published: June 2019

AbstractHuman observers perceptually discriminate the dynamic deformation of materials in the real world. However, the psychophysical and neural mechanisms responsible for the perception of dynamic deformation have not been fully elucidated. By using a deforming bar as the stimulus, we showed that the spatial frequency of deformation was a critical determinant of deformation perception. Simulating the response of direction-selective units (i.e., MT pattern motion cells) to stimuli, we found that the perception of dynamic deformation was well explained by assuming a higher-order mechanism monitoring the spatial pattern of direction responses. Our model with the higher-order mechanism also successfully explained the appearance of a visual illusion wherein a static bar apparently deforms against a tilted drifting grating. In particular, it was the lower spatial frequencies in this pattern that strongly contributed to the deformation perception. Finally, by manipulating the luminance of the static bar, we observed that the mechanism for the illusory deformation was more sensitive to luminance than contrast cues.Significance StatementFrom the psychophysical and computational points of view, the present study tried to answer the question, “how do human observers see deformation?”. In the psychophysical experiment, we used a clip wherein a bar dynamically deformed. We also tested the illusory deformation of a bar, which was caused by tilted drifting grating, because it was unclear whether the illusory deformation could be described by our model. In the computational analysis, in order to explain psychophysical data for deformation perception, it was necessary to assume an additional unit monitoring the spatial pattern of direction responses of MT cells that were sensitive to local image motion.
Investigating unexplained genetic variation and its expression in the arbuscular mycorrhizal fungus Rhizophagus irregularis
Authors: Masclaux Frédéric G. , Wyss Tania , Pagni Marco , Rosikiewicz Pawel , Sanders Ian R. 
Published: June 2019

SummaryArbuscular mycorrhizal fungi (AMF) are important symbionts of plants. Recently, studies of the AMF Rhizophagus irregularis recorded within-isolate genetic variation that does not completely match the proposed homokaryon or heterokaryon state (where heterokaryons comprise a population of two distinct nucleus genotypes). We re-analysed published data showing that bi-allelic sites (and their frequencies), detected in proposed homo- and heterokaryote R. irregularis isolates, were similar across independent studies using different techniques. This indicated that observed within-fungus genetic variation was not an artefact of sequencing and that such within-fungus genetic variation possibly exists. We looked to see if bi-allelic transcripts from three R. irregularis isolates matched those observed in the genome as this would give a strong indication of whether bi-allelic sites recorded in the genome were reliable variants. In putative homokaryon isolates, very few bi-allelic transcripts matched those in the genome. In a putative heterokaryon, a large number of bi-allelic transcripts matched those in the genome. Bi-allelic transcripts also occurred in the same frequency in the putative heterokaryon as predicted from allele frequency in the genome. Our results indicate that while within-fungus genome variation in putative homokaryon and heterokaryon AMF was highly similar in 2 independent studies, there was little support that this variation is transcribed in homokaryons. In contrast, within-fungus variation thought to be segregated among two nucleus genotypes in a heterokaryon isolate was indeed transcribed in a way that is proportional to that seen in the genome.
Experimental investigation of temperature-dependent denaturation behavior of type-I Collagen
Authors: Derman İ. Deniz , Şenel Esat C. , Ferhanoğlu Onur , Çilesiz İnci 
Published: June 2019

AbstractPrecise investigation of the temperature and the duration for collagen denaturation is critical for a number of applications, such as adjustment of temperature and duration during a laser-assisted tissue welding or collagen-based tissue repair products (films, implants, cross-linkers) preparation procedures. The result of such studies can serve as a guideline to mitigate potential side effects while maintaining the functionality of the collagen. Though a variety of collagen denaturation temperatures have been reported, there has not been a systematic study to report temperature-dependent denaturation rates. In this study, we perform a set of experiments on type-I collagen fiber bundles, extracted from the rat-tail tendon, and provide an Arrhenius model based on the acquired data. The tendons are introduced to buffer solutions having different temperatures, while monitoring the contrast in the crimp sights with a wide field microscope, where collagen fibers bend with respect to their original orientation. For all tested temperatures of 50°C–70 °C and tissues that were extracted from 5 rats, increasing the temperature reduced the contrast. On the average, we observed a decay of the contrast to half of its initial value at 37, 157, and 266 seconds when the collagen was introduced to 70 °C, 65 °C, and 60 °C buffer solutions, respectively. For the lower temperatures tested we only observed to be only about 20% and 2 % decay in the crimp contrast after > 2 hours at 55 °C and 50 °C, respectively. The observed denaturation behavior is also in line with Arrhenius Law, as expected. We are looking forward to expand this study to other types of collagen as a future work. Overall, with further development the data and model we present here could potentially serve as a guideline to determine limits for welding and manufacturing process of collagen-based tissue repair agents.
Asymmetric Cell Growth and Nucleoid Displacement inEscherichia coli
Authors: Gangan Manasi S. , Athale Chaitanya A. 
Published: June 2019

ABSTRACTSingle celled growth ofEscherichia coliis typically considered as an example symmetric division, based on the sizes of daughter cells and precision of center finding of the septum. Here, we investigate the symmetry of membrane addition in the mid-plane and DNA segregation using a video-microscopy approach. We find the membrane expansion dynamics to be asymmetric based on mid-cell photobleaching landmarks in FM4-64, used to stain the membrane. The apparent growth bias ofE. colidoes not correspond to the age of the pole. We find the membrane growth asymmetry is correlated to nucleoid displacement, consistent with ideas of coupling of cell growth and nucleoid positioning. The mobility of the actin-homolog MreB also correlates with membrane growth asymmetry, based on fluorescence recovery after photobleaching (FRAP) measurements of a YFP-fusion. These correlations suggest the small asymmetry of membrane addition observed could potentially drive nucleoid segregation and MreB mobility asymmetry inE. coli.IMPORTANCEAsymmetry in bacterial cell division is seen in it’s most simple form in the binomial event of protein segregation that results in ‘noise’ in equal segregation and depends on the protein copy number. In the case of specific proteins this can also affect growth, and result in differentiation. However, during the asexual division ofEscherichia colisingle cells are thought to grow symmetrically and divide equally. We find a slight but consistent asymmetry in growth based on quantitative morphometry of cell pole displacement in time-series of growingE. colicells. Increased cell wall extension in one half of the cell over the other appears to explain the asymmetry in the displacement of cell poles. Interestingly the growth asymmetry is not correlated to the age of the pole (old and new). This observed asymmetry appears to correlate with the asymmetry of nucleoid segregation, resulting in the nucleoids finding the midpoints of the respective daughter cells, and formation of the septum at the geometric centre of the elongated cell just prior to division. The mobility dynamics of the cytoskeletal protein MreB, which organizes the cell membrane, is are more dynamic where membrane growth is faster. Thus we propose a linkage between this observed growth asymmetry and that of MreB dynamics.
The evolutionary dynamics of Oropouche Virus (OROV) in South America
Authors: Gutierrez Bernardo , Wise Emma , Pullan Steven , Logue Christopher , Bowden Thomas A. , Trueba Gabriel , Nunes Marcio , Faria Nuno R. , Pybus Oliver G. 
Published: June 2019

AbstractThe Amazon basin is host to numerous arthropod-borne viral pathogens that cause febrile disease in humans. Among these,Oropouche orthobunyavirus(OROV) is a relatively understudied member of the Peribunyavirales that causes periodic outbreaks in human populations in Brazil and other South American countries. Although several studies have described the genetic diversity of the virus, the evolutionary processes that shape the viral genome remain poorly understood. Here we present a comprehensive study of the genomic dynamics of OROV that encompasses phylogenetic analysis, evolutionary rate estimates, inference of natural selective pressures, recombination and reassortment, and structural analysis of OROV variants. Our study includes all available published sequences, as well as a set of new OROV genomes sequences obtained from patients in Ecuador, representing the first set of viral genomes from this country. Our results show that differing evolutionary processes on the three segments that encompass the viral genome lead to variable evolutionary rates and TMRCAs that could be explained by cryptic reassortment. We also present the discovery of previously unobserved putative N-linked glycosylation sites, and codons which evolve under positive selection on the viral surface proteins, and discuss the potential role of these features in the evolution of the virus through a combined phylogenetic and structural approach.
Multi-tissue probabilistic fine-mapping of transcriptome-wide association study identifies cis-regulated genes for miserableness
Authors: Liao Calwing , Vuokila Veikko , Laporte Alexandre D , Spiegelman Dan , Dion Patrick A. , Rouleau Guy A. 
Published: June 2019

AbstractMiserableness is a behavioural trait that is characterized by strong negative feelings in an individual. Although environmental factors tend to invoke miserableness, it is common to feel miserable ‘for no reason’, suggesting an innate, potential genetic component. Currently, little is known about the functional relevance of common variants associated with miserableness. To further characterize the trait, we conducted a transcriptome-wide association study (TWAS) on 373,733 individuals and identified 104 signals across brain tissue panels with 37 unique genes. Subsequent probabilistic fine-mapping prioritized 95 genes into 90%-credible sets. Amongst these prioritized hits, C7orf50 had the highest posterior inclusion probability of 0.869 in the brain cortex. Furthermore, we demonstrate that many GWAS hits for miserableness are driven by expression. To conclude, we successfully identified several genes implicated in miserableness and highlighted the power of TWAS to prioritize genes associated with a trait.Short summaryThe first transcriptome-wide association study of miserableness identifies many
genes including c7orf50 implicated in the trait.
Neural Mechanisms of Economic Choices in Mice
Authors: Kuwabara Masaru , Holy Timothy E. , Padoa-Schioppa Camillo 
Published: June 2019

AbstractEconomic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of cells encoded the values of individual options, the binary choice outcome and the chosen value. These groups match those previously identified in primates, except that the neuronal representation in mice is spatial (in monkeys it is good-based). Our results lay the foundations for a circuit-level analysis of economic decisions.
A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease
Authors: Preuss Christoph , Pandey Ravi , Piazza Erin , Fine Alexander , Uyar Asli , Perumal Thanneer , Garceau Dylan , Kotredes Kevin P , Williams Harriet , Mangravite Lara M , Lamb Bruce T. , Oblak Adrian L. , Howell Gareth R. , Sasner Michael , Logsdon Benjamin A , Carter Gregory W. 
Published: June 2019

ABSTRACTBackgroundLate-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer’s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes.ResultsThis resource enables precise gene-based alignment between new animal models and human molecular signatures of disease. Here, we describe a new resource to efficiently screen mouse models for LOAD relevance. A new NanoString nCounter® Mouse AD panel was designed to correlate key human disease processes and pathways with mRNA from mouse brains. Analysis of three mouse models based on LOAD genetics, carrying APOE4 and TREM2*R47H alleles, demonstrated overlaps with distinct human AD modules that, in turn, are functionally enriched in key disease-associated pathways. Comprehensive comparison with full transcriptome data from same-sample RNA-Seq shows strong correlation between gene expression changes independent of experimental platform.ConclusionsTaken together, we show that the nCounter Mouse AD panel offers a rapid, cost-effective and highly reproducible approach to assess disease relevance of potential LOAD mouse models.
Control of Intracellular Molecular Networks Using Algebraic Methods
Authors: Vieira Luis Sordo , Laubenbacher Reinhard C. , Murrugarra David 
Published: June 2019

AbstractMany problems in biology and medicine have a control component. Often, the goal might be to modify intracellular networks, such as gene regulatory networks or signaling networks, in order for cells to achieve a certain phenotype, such as happens in cancer. If the network is represented by a mathematical model for which mathematical control approaches are available, such as systems of ordinary differential equations, then this problem might be solved systematically. Such approaches are available for some other model types, such as Boolean networks, where structure-based approaches have been developed, as well as stable motif techniques.However, increasingly many published discrete models are mixed-state or multistate, that is, some or all variables have more than two states, and thus the development of control strategies for multistate networks is needed. This paper presents a control approach broadly applicable to general multistate models based on encoding them as polynomial dynamical systems over a finite algebraic state set, and using computational algebra for finding appropriate intervention strategies. To demonstrate the feasibility and applicability of this method, we apply it to a recently developed multistate intracellular model of E2F-mediated bladder cancerous growth, and to a model linking intracellular iron metabolism and oncogenic pathways. The control strategies identified for these published models are novel in some cases and represent new hypotheses, or are supported by the literature in others as potential drug targets.Our Macaulay2 scripts to find control strategies are publicly available through GitHub at https://github.com/luissv7/multistatepdscontrol.
HB-EGF Signaling is Required for Glucose-Induced Pancreatic β-Cell Proliferation in Rats
Authors: Maachi Hasna , Fergusson Grace , Ethier Melanie , Brill Gabriel N. , Katz Liora S. , Honig Lee B. , Metukuri Mallikarjuna R. , Scott Donald K. , Ghislain Julien , Poitout Vincent 
Published: June 2019

ABSTRACTThe molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on Epidermal Growth Factor Receptor (EGFR) signaling. The aim of this study was to determine the role of the EGFR ligand Heparin-Binding EGF-like Growth Factor (HB-EGF) in the β-cell proliferative response to glucose, a β-cell mitogen and key regulator of β-cell mass in response to increased insulin demand. We show that exposure of isolated rat and human islets to HB-EGF stimulates β-cell proliferation. In rat islets, inhibition of EGFR or HB-EGF blocks the proliferative response not only to HB-EGF but also to glucose. Furthermore, knockdown of HB-EGF in rat islets blocks β-cell proliferation in response to glucose ex vivo and in vivo in transplanted glucose-infused rats. Mechanistically, we demonstrate that HB-EGF mRNA levels are increased in β cells in response to glucose in a Carbohydrate Response Element Binding Protein (ChREBP)-dependent manner. In addition, chromatin-immunoprecipitation studies identified ChREBP binding sites in proximity to the HB-EGF gene. Finally, inhibition of Src family kinases, known to be involved in HB-EGF processing, abrogated glucose-induced β-cell proliferation. Our findings identify a novel glucose/HB-EGF/EGFR axis implicated in β-cell compensation to increased metabolic demand.