bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bumblebee visual allometry results in locally improved resolution and globally improved sensitivity
Authors: Taylor Gavin J. , Tichit Pierre , Schmidt Marie D. , Bodey Andrew J. , Rau Christoph , Baird Emily 
Published: July 2018

AbstractThe quality of visual information that is available to an animal is limited by the size of its eyes. Differences in eye size can be observed even between closely related individuals but we understand little about how this affects visual quality. Insects are good models for exploring the effects of size on visual systems because many species exhibit size polymorphism, which modifies both the size and shape of their eyes. Previous work in this area has been limited, however, due to the challenge of determining the 3D structure of eyes. To address this, we have developed a novel method based on x-ray tomography to measure the 3D structure of insect eyes and calculate their visual capabilities. We investigated visual allometry in the bumblebeeBombus terrestrisand found that size affects specific aspects of visual quality including binocular overlap, optical sensitivity across the field of view, and visual resolution in the dorsofrontal visual field. This holistic study on eye allometry reveals that differential scaling between different eye areas provides substantial flexibility for larger bumblebees to have improved visual capabilities.
Exogenous attention facilitates performance through dissociable sensitivity and bias mechanisms
Authors: Sagar Vishak , Sengupta Ranit , Sridharan Devarajan 
Published: July 2018

AbstractSelective attention enables prioritizing the most important information for differential sensory processing and decision-making. Here, we address an active debate regarding whether attention reflects a unitary phenomenon or involves the operation of dissociable sensory enhancement (perceptual sensitivity) and decisional gating (choice bias) processes. We developed a multialternative task in which participants detected and localized orientation changes in gratings at one of four spatial locations. Exogenous attention cues (high contrast flashes) preceded or followed the change events in close temporal proximity. Analysis of participants’ behavior with a multidimensional signal detection model revealed markedly distinct effects of exogenous cueing on perceptual sensitivity and choice bias. Whereas sensitivity enhancement was localized to the stimulus proximal to the exogenous cue, bias enhancement occurred even for distal stimuli in the cued hemifield. Modulations of sensitivity and bias were uncorrelated at both cued and uncued locations. Finally, exogenous cueing produced reaction time benefits only at the cued location and costs only at locations contralateral to the cue. These disparate effects of exogenous cueing on sensitivity, bias and reaction times could be parsimoniously explained within the framework of a diffusion-decision model, in which the drift rate was determined by a linear combination of sensitivity and bias at each location. Exogenous cueing effects on sensitivity and bias differed systematically from previously reported effects of endogenous cueing. We propose that the search for shared neural substrates of exogenous and endogenous attention would benefit from investigating neural correlates of their component sensory and decisional mechanisms.Significance statementWhen we voluntarily direct attention “endogenously”, we are able to better perceive stimuli at the attended location (sensitivity), and to prioritize information from that location for guiding behavioral decisions (bias). But when a salient stimulus, such as a flash of lightning, captures our attention “exogenously”, does it also produce these same effects? To answer this question, we designed a multiple alternative task in which task events occurred in close conjunction with salient exogenous cues (high contrast flashes). We discovered that exogenous attention enhanced both sensitivity and bias for cued stimuli, but each of these changes followed distinct spatial patterns across locations. Our results provide novel insights into component processes of exogenous attention and motivate the search for their neural correlates.
Genome sequence of the wheat stem sawfly, Cephus cinctus, a primitive hymenopteran and wheat pest, illuminates evolution of hymenopteran chemoreceptors
Authors: Robertson Hugh M. , Waterhouse Robert M. , Walden Kimberly K. O. , Ruzzante Livio , Reijnders Maarten J. M. F. , Coates Brad S. , Legeai Fabrice , Gress Joanna C. , Biyiklioglu Sezgi , Weaver David K. , Wanner Kevin W. , Budak Hikmet 
Published: July 2018

AbstractThe wheat stem sawfly, Cephus cinctus, is a major pest of wheat and key ecological player in the grasslands of western North America. It also represents a distinctive lineage of sawflies that appeared early during the hymenopteran radiation, but after the clade of Eusymphyta sawflies that is the sister lineage of all other Hymenoptera. We present a high-quality draft genome assembly of 162 Mbp in 1,976 scaffolds with a scaffold N50 of 622 kbp. Automated gene annotation identified 11,210 protein-coding gene models and 1,307 non-coding RNA models. Thirteen percent of the assembly consists of ~58,000 transposable elements partitioned equally between Class-I and Class-II elements. Orthology analysis reveals that 86% of Cephus proteins have identifiable orthologs in other insects. Phylogenomic analysis of conserved subsets of these proteins supports the placement of the Cephidae between the Eusymphyta and the parasitic woodwasp superfamily Orussoidea. Manual annotation and phylogenetic analysis of families of odorant, gustatory, and ionotropic receptors, plus odorant binding proteins, shows that Cephus has representatives for most conserved and expanded gene lineages in the Apocrita (wasps, ants, and bees). Cephus has also maintained several insect gene lineages that have been lost from the Apocrita, most prominently the carbon dioxide receptor subfamily. Furthermore, Cephus encodes a few small lineage-specific chemoreceptor gene family expansions that might be involved in adaptations to new grasses including wheat. These comparative analyses identify gene family members likely to have been present in the hymenopteran ancestor and provide a new perspective on the evolution of the chemosensory gene repertoire.
Heterozygous mutations in p97 and resistance to p97 inhibitors
Authors: Bastola Prabhakar , Minn Kay , Chien Jeremy 
Published: July 2018

AbstractIn recent years, multiple studies including ours have reported on the mechanism of resistance towards p97 inhibitors. While all these studies outline target alteration via mutations in p97 as the primary mechanism of resistance, discrepancies persist in the current literature due to the occurrence of both heterozygous and homozygous mutations when using HCT116 cells. Here, we report a pre-existing heterozygous frameshift mutation at codon 616 (N616fs*) in one of the p97 alleles in HCT116 cells and show that this mutant allele is subjected to nonsense-mediated decay. Furthermore, we independently generated p97 inhibitor (CB-5083) resistant HCT116 cells, and we observed a single heterozygous mutation at codon 526 (L526S) in genomic DNA sequencing but a homozygous L526S mutation in complementary DNA sequencing, indicating that the missense mutation (L526S) occurs in the allele that does not harbor the frameshift N616fs* mutation. Our results underscore the importance of performing simultaneous genomic and complementary DNA sequencing when confirming mutations in p97.
Molecular Diversity of Intrinsically Photosensitive Ganglion Cells
Authors: Berg Daniel , Kartheiser Katherine , Leyrer Megan , Saali Alexandra , Berson David 
Published: July 2018

AbstractIntrinsically photosensitive retinal ganglion cells (ipRGCs) are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. They comprise multiple subtypes distinguishable by morphology, physiology, projections, and levels of expression of melanopsin (Opn4), their photopigment. The molecular programs that differentiate ipRGCs from other ganglion cells and ipRGC subtypes from one another remain elusive. Here, we present comprehensive gene expression profiles of early postnatal and adult mouse ipRGCs purified from two lines of reporter mice marking different sets of ipRGC subtypes. We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are unexpectedly diverse at the molecular level. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes.
High-resolution 4D spatiotemporal analysis reveals the contributions of local growth dynamics to contrasting maize root architectures
Authors: Jiang Ni , Floro Eric , Bray Adam L. , Laws Benjamin , Duncan Keith E. , Topp Christopher N. 
Published: July 2018

ABSTRACTRoot systems are branched networks that develop from simple growth properties of their individual roots. Yet a mature maize root system has many thousands of roots that each interact with soil structures, water and nutrient patches, and microbial ecologies in the micro-environments surrounding each root tip. Although the plasticity of root growth to these and other environmental factors is well known, how the many local processes contribute over time to global features of root system architecture is hardly understood. We employ an automated 3D root imaging pipeline to capture the growth of maize roots every four hours throughout seven days of seedling development. We model the contrasting architectures of two maize inbred genotypes and their hybrid to derive key parameters that distinguish complex growth patterns as a function of time. The statistical characteristics of local root growth defined the global system properties despite a large range of trait values. “Computational dissection” of a single root from each root system identified differences in the size of the root branching zone and lateral branching densities, but not radial patterns, that drove the contrasting root architectures from seedling to maturity. X-ray imaging of mature field-grown root crowns showed that seedling growth trajectories persisted throughout development and could predict eventual architectures, suggesting a strong genetic basis. The work connects individual and systemwide scales of root growth dynamics, providing the means for a function-valued approach to understanding the genetic and genetic x environment conditioning of root growth that will enable breeding for enhanced root traits.SIGNIFICANCE STATEMENTWhen and where roots grow determines their ability to capture short-lived and patchy water and nutrient resources to support the aboveground organs of the plant. Roots have no known long-distance external sensing mechanisms, but form branched networks that blindly explore the soil and respond to encountered local stimuli. How global architectures form from the many thousands of these local responses, and how they are controlled genetically are major open questions. Here we quantify differences in local root growth patterns of two inbred genotypes of maize that control contrasting systemwide properties. Measurements at the seedling stage were highly correlated with the complex architectures of mature root systems, paving the way for the development of crops with greater resource uptake capacity.
A Robust Method to Estimate the Largest Lyapunov Exponent of Noisy Signals: A Revision to the Rosenstein’s Algorithm
Authors: Mehdizadeh Sina 
Published: July 2018

AbstractAimThis study proposed a revision to the Rosenstein’s method of numerical calculation of largest Lyapunov exponent (LyE) to make it more robust to noise.MethodsTo this aim, the effect of increasing number of initial neighboring points on the LyE value was investigated and compared to the values obtained by filtering the time series. Both simulated (Lorenz and passive dynamic walker) and experimental (human walking) time series were used to calculate LyE. The number of initial neighbors used to calculate LyE for all time series was 1 (the original Rosenstein’s method), 2, 3, 4, 5, 10, 15, 20, 25, and 30 data points.ResultsThe results demonstrated that the LyE graph reached a plateau at the 15-point neighboring condition inferring that the LyE values calculated using at least 15 neighboring points were consistent and reliable.ConclusionThe proposed method could be used to calculate LyE more reliably in experimental time series acquired from biological systems where noise is omnipresent.
Mitochondrial RNA capping: highly efficient 5’-RNA capping with NAD+ and NADH by yeast and human mitochondrial RNA polymerase
Authors: Bird Jeremy G. , Basu Urmimala , Kuster David , Ramachandran Aparna , Grudzien-Nogalska Ewa , Kiledjian Megerditch , Temiakov Dmitry , Patel Smita S. , Ebright Richard H. , Nickels Bryce E. 
Published: July 2018

AbstractBacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~10% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at, and upstream of, the transcription start site and, in yeast and human cells, by intracellular NAD+ and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial gene expression, sensing NAD+ and NADH levels and adjusting transcriptional outputs accordingly.
In silicoprioritization of transporter-drug relationships from drug sensitivity screens
Authors: César-Razquin A. , Girardi E. , Yang M. , Brehme M. , Sáez-Rodríguez J. , Superti-Furga G. 
Published: July 2018

AbstractThe interplay between drugs and cell metabolism is a key factor in determining both compound potency and toxicity. In particular, how and to what extent transmembrane transporters affect drug uptake and disposition is currently only partially understood. Most transporter proteins belong to two protein families: the ATP-Binding Cassette (ABC) transporter family, whose members are often involved in xenobiotic efflux and drug resistance, and the large and heterogeneous family of Solute carriers (SLCs). We recently argued that SLCs are collectively a rather neglected gene group, with most of its members still poorly characterized, and thus likely to include many yet-to-be-discovered associations with drugs. We searched publicly available resources and literature to define the currently known set of drugs transported by ABCs or SLCs, which involved ~500 drugs and more than 100 transporters. In order to extend this set, we then mined the largest publicly available pharmacogenomics dataset, which involves approximately 1000 molecularly annotated cancer cell lines and their response to 265 chemical compounds, and used regularized linear regression models (Elastic Net, LASSO) to predict drug responses based on SLC and ABC data (expression levels, SNVs, CNVs). The most predictive models included both known and previously unidentified associations between drugs and transporters. To our knowledge, this represents the first application of regularized linear regression to this set of genes, providing an extensive prioritization of potentially pharmacologically interesting interactions.
Quick and efficient approach to develop genomic resources in orphan species: application inLavandula angustifolia
Authors: Fomeju Berline Fopa , Brunel Dominique , Bérard Aurélie , Rivoal Jean-Baptiste , Gallois Philippe , Le Paslier Marie-Christine , Bouverat-Bernier Jean-Pierre 
Published: July 2018

AbstractNext-Generation Sequencing (NGS) technologies, by reducing the cost and increasing the throughput of sequencing, have opened doors of research efforts to generate genomic data to a range of previously poorly studied species. In this study, we proposed a method for the rapid development of a large scale molecular resources for orphan species. We studied as an exampleLavandula angustifolia, a perennial sub-shrub plant native from the Mediterranean region and whose essential oil have numerous applications in cosmetics, pharmaceuticals, and alternative medicines.We first built a ‘Maillette’ reference Unigene, compound of coding sequences, thanks tode novoRNA-seq assembly. Then, we reconstructed the complete genes sequences (with exons and introns) using a transcriptome-guided DNA-seq assembly approach in order to maximize the possibilities of finding polymorphism between genetically close individuals. Finally, we used these resources for SNP mining within a collection of 16 lavender clones and tested the SNP within the scope of a phylogeny analysis. We obtained a cleaned reference of 8, 030 functionally annotated ‘genes’ (in silicoannotation). We found up to 400K polymorphic sites, depending on the genotype analyzed, and observed a high SNP frequency (mean of 1 SNP per 90 bp) and a high level of heterozygosity (more than 60% of heterozygous SNP per genotype). We found similar genetic distances between pairs of clones, related to the out-crossing nature of the species, the restricted area of cultivation and the clonal propagation of the varieties.The method propose is transferable to other orphan species, requires little bioinformatics resources and can be realized within a year. This is the first reported large-scale SNP development on Lavandula angustifolia. All this data provides a rich pool of molecular resource to explore and exploit biodiversity in breeding programs.
Genome-wide silencing screen in mesothelioma cells reveals that loss of function of BAP1 induces chemoresistance to ribonucleotide reductase inhibition: implication for therapy
Authors: Okonska Agata , Bühler Saskja , Rao Vasundhara , Ronner Manuel , Blijlevens Maxime , Meulen-Muileman Ida Van der , Menezes Renee de , Smit Egbert , Weder Walter , Stahel Rolf , Penengo Lorenza , Beusechem Victor van , Felley-Bosco Emanuela 
Published: July 2018

ABSTRACTIntroductionLoss of function of BRCA1 associated protein 1 (BAP1) is observed in about 50% of malignant pleural mesothelioma (MPM) cases. The aim of this study was to investigate whether this aspect could be exploited for targeted therapy.MethodsA genetically engineered model was established expressing either functional or nonfunctional BAP1 and whole-genome siRNA screens were performed assessing impaired survival between the two cell lines. Cytotoxity induced by gemcitabine and hydroxyurea were assessed in a panel of BAP1-WT and BAP1-mut/del cell lines. Functional studies were carried out in BAP1 mut/del cell line reconstituted with BAP1 WT or BAP1 C91A (catalytically dead mutant) and in BAP1 WT cell line upon siRNA-mediated knock-down of BAP1.ResultsThe whole-genome siRNA screen unexpectedly revealed 11 hits (FDR<0.05) more cytotoxic for BAP1-proficient cells. Two actionable targets, RRM1 and RRM2, were validated and their inhibition mediated by gemcitabine or hydroxyurea respectively, was more cytotoxic in BAP1-proficient cell lines. Upregulation of RRM2 upon gemcitabine and hydroxyurea was more profound in BAP1 mut/del cell lines. Increased lethality mediated by gemcitabine and hydroxyurea was observed in NCI-H2452 cells reconstituted with BAP1 WT but not with C91A mutant and upregulation of RRM2 in NCI-H2452-BAP1 WT spheroids was modest compared to control or C91A mutant. Finally, the opposite was observed after BAP1 knockdown in BAP1-proficient SPC111 cell line.ConclusionWe found that BAP1 is involved in the regulation of RRM2 levels during replication stress. These observations reveal a potential therapeutic approach where MPM patients to be stratified depending on BAP status for gemcitabine treatment.
Low genetic variation is associated with low mutation rate in the giant duckweed
Authors: Xu Shuqing , Stapley Jessica , Gablenz Saskia , Boyer Justin , Appenroth Klaus J. , Sree K. Sowjanya , Gershenzon Jonathan , Widmer Alex , Huber Meret 
Published: July 2018

AbstractMutation rate and effective population size (Ne) jointly determine intraspecific genetic diversity, but the role of mutation rate is often ignored. We investigate genetic diversity, spontaneous mutation rate andNein the giant duckweed (Spirodela polyrhiza). Despite its large census population size, whole-genome sequencing of 68 globally sampled individuals revealed extremely low within-species genetic diversity. Assessed under natural conditions, the genome-wide spontaneous mutation rate is at least seven times lower than estimates made for other multicellular eukaryotes, whereasNeis large. These results demonstrate that low genetic diversity can be associated with large-Nespecies, where selection can reduce mutation rates to very low levels, and accurate estimates of mutation rate can help to explain seemingly counterintuitive patterns of genome-wide variation.One Sentence SummaryThe low-down on a tiny plant: extremely low genetic diversity in an aquatic plant is associated with its exceptionally low mutation rate.
Investigating the unknown functions in the minimal bacterial genome reveals many transporter proteins
Authors: Antczak Magdalena , Michaelis Martin , Wass Mark N 
Published: July 2018

AbstractThe recent identification of the minimal bacterial genome revealed that nearly one third (149) of the 473 encoded genes were of unknown function, demonstrating our limited understanding of the essential functions of life. Application of state of the art in silico methods for functional annotation demonstrated that these proteins of unknown function lack orthologs, known protein domains, and templates to model their structure. Combination of the results from different complementary approaches enabled functions to be assigned to 94 of the 149 proteins, although often with general terms such as transporter or DNA binding. 22 likely transporter proteins were identified indicating the importance of nutrient uptake into and waste disposal out of the minimal bacterial cell, where many metabolic enzymes have been removed. These results advance our understanding of the minimal bacterial genome and therefore aid synthetic biology and its application to biotechnology.