bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse food-sensing neurons trigger idiothetic local search in Drosophila
Authors: Corfas Román A. , Dickinson Michael H. 
Published: October 2018

ABSTRACTResources are often sparsely clustered in nature. Thus, foraging animals may benefit from remembering the location of a newly discovered food patch while continuing to explore nearby [1, 2]. For example, after encountering a drop of yeast or sugar, hungry flies often perform a local search consisting of frequent departures and returns to the food site [3, 4]. Fruit flies, Drosophila melanogaster, can perform this food-centered search behavior in the absence of external stimuli or landmarks, instead relying solely on internal (idiothetic) cues to keep track of their location [5]. This path integration behavior may represent a deeply conserved navigational capacity in insects [6, 7], but the neural pathways underlying food-triggered searches remain unknown. Here, we used optogenetic activation to screen candidate cell classes and found that local searches can be initiated by diverse sensory neurons including sugar-sensors, water-sensors, olfactory-receptor neurons, as well as hunger-signaling neurons of the central nervous system. Optogenetically-induced searches resemble those triggered by actual food and are modulated by starvation state. Furthermore, search trajectories exhibit key features of path integration: searches remain tightly centered around the fictive-food site, even during long periods without reinforcement, and flies re-center their searches when they encounter a new fictive-food site. Flies can even perform elaborate local searches within a constrained maze. Together, these results suggest that flies enact local searches in response to a wide variety of food-associated cues, and that these sensory pathways may converge upon a common neural system for path integration. Optogenetically induced local searches in Drosophila can now serve as a tractable system for the study of spatial memory and navigation in insects.
A Bayesian psychophysics model of sense of agency
Authors: Legaspi Roberto , Toyoizumi Taro 
Published: October 2018

AbstractDespite the increasing significance of sense of agency (SoA) research, the literature lacks a formal model: what computational principles underlie SoA, the registration that oneself initiated an action that caused something to happen? We theorize SoA in the framework of optimal Bayesian cue integration with mutually involved principles, namely, reliability of action and outcome sensory signals, their consistency with the causation of the outcome by the action, and the prior belief in causation. We used our Bayesian model to explain the intentional binding effect, hailed as reliable indicator of SoA. Our model explains temporal binding in both self-intended and unintentional actions suggesting that intentionality is not strictly necessary given high confidence in the action causing the outcome. Our Bayesian model also explains that if the sensory cues are reliable, SoA can emerge even for unintended actions. Our formal model therefore posits a precision-dependent causal agency.
The Effects of Global Signal Regression on Estimates of Resting-state BOLD fMRI and EEG Vigilance Correlations
Authors: Falahpour Maryam , Nalci Alican , Liu Thomas T. 
Published: October 2018

AbstractGlobal signal regression (GSR) is a commonly used albeit controversial preprocessing approach in the analysis of resting-state BOLD fMRI data. While the effects of GSR on resting-state functional connectivity measures have received much attention, there has been relatively little attention devoted to its effects on studies looking at the relation between resting-state BOLD measures and independent measures of brain activity. In this study we used simultaneously acquired EEG-fMRI data in humans to examine the effects of GSR on the correlation between resting-state BOLD fluctuations and EEG vigilance measures. We show that GSR leads to a positive shift in the correlation between the BOLD and vigilance measures. This shift leads to a reduction in the spatial extent of negative correlations in widespread brain areas, including the visual cortex, but leads to the appearance of positive correlations in other areas, such as the cingulate gyrus. The results obtained using GSR are consistent with those of a temporal censoring process in which the correlation is computed using a temporal subset of the data. Since the data from these retained time points are unaffected by the censoring process, this finding suggests that the positive correlations in cingulate gyrus are not simply an artifact of GSR.
Histone deacetylase inhibitor treatment promotes spontaneous caregiving behavior in C57BL/6J male mice
Authors: Mayer H.S. , Crepeau M. , Duque-Wilckens N. , Torres L.Y. , Trainor B.C. , Stolzenberg D.S. 
Published: October 2018

AbstractWhereas the majority of mammalian species are uni-parental with the mother solely provisioning care for young conspecifics, fathering behaviors can emerge under certain circumstances. For example, a great deal of individual variation in response to young pups has been reported in multiple inbred strains of laboratory male mice. Further, sexual experience and subsequent cohabitation with a female conspecific can induce caregiving responses in otherwise indifferent, fearful or aggressive males. Thus, a highly conserved parental neural circuit is likely present in both sexes, however the extent to which infants are capable of accessing this circuit may vary. In support of this idea, fearful or indifferent responses toward pups in female mice are linked to greater immediate early gene (IEG) expression in a fear/defensive circuit involving the anterior hypothalamus than in an approach/attraction circuit involving the ventral tegmental area. However, experience with infants, particularly in combination with histone deacetylase inhibitor (HDACi) treatment, can reverse this pattern of neuronal activation and behavior. Thus, HDACi treatment may increase the transcription of primed/poised genes that play a role in the activation and selection of a maternal approach circuit in response to pup stimuli. Here, we asked whether HDACi treatment would impact behavioral response selection and associated IEG expression changes in virgin male mice that are capable of ignoring, attacking or caring for pups. Our results indicate that systemic HDACi treatment induces spontaneous caregiving behavior in non-aggressive male mice and alters the pattern of pup-induced IEG expression across a fear/defensive neural circuit.
One Health genomic surveillance ofEscherichia colidemonstrates distinct lineages and mobile genetic elements in isolates from humans versus livestock
Authors: Ludden Catherine , Raven Kathy E. , Jamrozy Dorota , Gouliouris Theodore , Blane Beth , Coll Francesc , de Goffau Marcus , Naydenova Plamena , Horner Carolyne , Hernandez-Garcia Juan , Wood Paul , Hadjirin Nazreen , Radakovic Milorad , Brown Nicholas M. , Holmes Mark , Parkhill Julian , Peacock Sharon J. 
Published: October 2018

ABSTRACTLivestock have been proposed as a reservoir for drug-resistantEscherichia colithat infect humans. We isolated and sequenced 431E. coli(including 155 ESBL-producing isolates) from cross-sectional surveys of livestock farms and retail meat in the East of England. These were compared with the genomes of 1517E. coliassociated with bloodstream infection in the United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and patient isolates were genetically distinct, indicating thatE. colicausing serious human infection do not directly originate from livestock. By contrast, we observed highly related isolates from the same animal species on different farms. Analysis of accessory (variable) genomes identified a virulence cassette associated previously with cystitis and neonatal meningitis that was only present in isolates from humans. Screening all 1948 isolates for accessory genes encoding antibiotic resistance revealed 41 different genes present in variable proportions of humans and livestock isolates. We identified a low prevalence of shared antimicrobial resistance genes between livestock and humans based on analysis of mobile genetic elements and long-read sequencing. We conclude that in this setting, there was limited evidence to support the suggestion that antimicrobial resistant pathogens that cause serious infection in humans originate from livestock.ImportanceThe increasing prevalence ofE. colibloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources ofE. coliassociated with serious human disease.E. colifrom 1517 patients with bloodstream infection were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was little overlap in the mobile elements carrying these genes. In addition, a virulence cassette found in humans isolates was not identified in any livestock-associated isolate. Our findings do not support the idea thatE. colicausing invasive disease or their resistance genes are commonly acquired from livestock.
Effects of radiofrequency electromagnetic radiation (RF-EMF) on honey bee queen development and mating success
Authors: Odemer Richard , Odemer Franziska 
Published: October 2018

ABSTRACTMobile phones can be found almost everywhere across the globe, upholding a direct point-to-point connection between the device and the broadcast tower. The emission of radiofrequency electromagnetic radiation (RF-EMF) puts the surrounding environment inevitably into contact with this pollutant. We have therefore exposed honey bee queen larvae to the radiation of a common mobile phone device (GSM) during all stages of their pre-adult development including pupation. After 14 days of exposure, hatching of adult queens was assessed and mating success after further 11 days, respectively. Moreover, full colonies were established of five of the untreated and four of the treated queens to contrast population dynamics. We found that mobile phone radiation had significantly reduced the hatching ratio but not the mating success. If treated queens were successfully mated, colony development was not adversely affected. We provide evidence that RF-EMF only acts detrimental within the sensitivity of pupal development, once succeeded this point, no further impairment has manifested in adulthood. Our results are discussed against the background of long-lasting consequences for colony performance and the possible implication on periodic colony losses.HIGHLIGHTSChronic RF-EMF exposure significantly reduced hatching of honey bee queensMortalities occurred during pupation, not at the larval stagesMating success was not adversely affected by the irradiationAfter the exposure, surviving queens were able to establish intact coloniesGRAPHICAL ABSTRACT
The promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 primate-specific endogenous retrovirus: an evolutionary connection between immunity and cognition
Authors: Nataf Serge , Uriagereka Juan , Benitez-Burraco Antonio 
Published: October 2018

ABSTRACTSocial behavior and neuronal connectivity in rodents have been shown to be shaped by the prototypical T lymphocyte-derived pro-inflammatory cytokine Interferon-gamma (IFNγ). It has also been demonstrated that STAT1 (Signal Transducer And Activator Of Transcription 1), a transcription factor (TF) crucially involved in the IFNγ pathway, binds consensus sequences that, in humans, are located with a high frequency in the LTRs (Long Terminal Repeats) of the MER41 family of primate-specific HERVs (Human Endogenous Retrovirus). However, the putative role of an IFNγ/STAT1/MER41 pathway in human cognition and/or behavior is still poorly documented. Here, we present evidence that the promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 HERVs. This observation is specific to MER41 among more than 130 HERVs examined. Moreover, we have not found such a significant enrichment in the promoter regions of genes that associate with autism spectrum disorder (ASD) or schizophrenia. Interestingly, ID-associated genes exhibit promoter-localized MER41 LTRs that harbor TF binding sites (TFBSs) for not only STAT1 but also other immune TFs such as, in particular, NFKB1 (Nuclear Factor Kappa B Subunit 1) and STAT3 (Signal Transducer And Activator Of Transcription 3). Moreover, IL-6 (Interleukin 6) rather than IFNγ, is identified as the main candidate cytokine regulating such an immune/MER41/cognition pathway. Of note, functionally-relevant differences between humans and chimpanzees are observed regarding the 3 main components of this pathway: i) the protein sequences of immunes TFs binding MER41 LTRs, ii) the insertion sites of MER41 LTRs in the promoter regions of ID-associated genes and iii) the protein sequences of the targeted ID-associated genes. Finally, a survey of the human proteome has allowed us to map a protein-protein network which links the identified immune/MER41/cognition pathway to FOXP2 (Forkhead Box P2), a key TF involved in the emergence of human speech. Together, these results suggest that the stepped self-domestication of MER41 in the genomes of primates could have been a driver of cognitive evolution. Our data further indicate that non-inherited forms of ID might result from alterations of the immune/MER41/cognition pathway induced notably by the untimely or quantitatively inappropriate exposure of human neurons to IL-6.
Modeling visual performance differences with polar angle: A computational observer approach
Authors: Kupers Eline R. , Carrasco Marisa , Winawer Jonathan 
Published: October 2018

AbstractVisual performance depends on polar angle, even when eccentricity is held constant; on many psychophysical tasks observers perform best when stimuli are presented on the horizontal meridian, worst on the upper vertical, and intermediate on the lower vertical meridian. This variation in performance ‘around’ the visual field can be as pronounced as that of doubling the stimulus eccentricity. The causes of these asymmetries in performance are largely unknown. Some factors in the eye, e.g. cone density, are positively correlated with the reported variations in visual performance with polar angle. However, the question remains whether such correlations can quantitatively explain the perceptual differences observed ‘around’ the visual field. To investigate the extent to which the earliest stages of vision –optical quality and cone density- contribute to performance differences with polar angle, we created a computational observer model. The model uses the open-source software package ISETBIO to simulate an orientation discrimination task for which visual performance differs with polar angle. The model starts from the photons emitted by a display, which pass through simulated human optics with fixational eye movements, followed by cone isomerizations in the retina. Finally, we classify stimulus orientation using a support vector machine to learn a linear classifier on the photon absorptions. To account for the 30% increase in contrast thresholds for upper vertical compared to horizontal meridian, as observed psychophysically on the same task, our computational observer model would require either an increase of ~7 diopters of defocus or a reduction of 500% in cone density. These values far exceed the actual variations as a function of polar angle observed in human eyes. Therefore, we conclude that these factors in the eye only account for a small fraction of differences in visual performance with polar angle. Substantial additional asymmetries must arise in later retinal and/or cortical processing.Author SummaryA fundamental goal in computational neuroscience is to link known facts from biology with behavior. Here, we considered visual behavior, specifically the fact that people are better at visual tasks performed to the left or right of the center of gaze, compared to above or below at the same distance from gaze. We sought to understand what aspects of biology govern this fundamental pattern in visual behavior. To do so, we implemented a computational observer model that incorporates known facts about the front end of the human visual system, including optics, eye movements, and the photoreceptor array in the retina. We found that even though some of these properties arecorrelatedwith performance, they fall far short ofquantitatively explaining it. We conclude that later stages of processing in the nervous system greatly amplify small differences in the way the eye samples the visual world, resulting in strikingly different performance around the visual field.
Investigating the relationship between insecticide resistance, underlying molecular mechanisms and malaria prevalence in Anopheles gambiae s.l. from Guinea
Authors: Collins Emma , Vaselli Natasha M. , Sylla Moussa , Beavogui Abdoul H. , Orsborne James , Walker Thomas , Messenger Louisa A. 
Published: October 2018

AbstractThe threat of insecticide resistance across sub-Saharan Africa is anticipated to severely impact the continued effectiveness of malaria vector control. We investigated the effect of carbamate and pyrethroid resistance on Anopheles gambiae s.l age, Plasmodium falciparum infection and characterized molecular resistance mechanisms in Guinea. Pyrethroid resistance was intense, with survivors of ten times the insecticidal concentration required to kill susceptible individuals. The L1014F kdr allele was significantly associated with mosquito survival following deltamethrin or permethrin treatment (p=0.003 and p=0.04, respectively). N1575Y and I1527T mutations were identified in 13% and 10% of individuals, respectively, but neither conferred increased pyrethroid tolerance. Partial restoration of pyrethroid susceptibility following synergist pre-exposure suggest a role for mixed-function oxidases. Carbamate resistance was lower and significantly associated with the G119S Ace-1 mutation (p=0.001). Oocyst rates were 6.8% and 4.2% among resistant and susceptible mosquitoes, respectively; survivors of bendiocarb exposure were significantly more likely to be infected (p=0.03). Resistant mosquitoes had significantly lower parity rates; however, a subset of intensely pyrethroid-resistant vectors were more likely to be parous (p=0.042 and p=0.045, for survivors of five and ten times the diagnostic dose of insecticides, respectively). Our findings emphasize the need for additional studies directly assessing the influence of insecticide resistance on mosquito fitness.
Design of an epitope-based peptide vaccine againstCryptococcus neoformans
Authors: Khalil Isra , Omer Ibtihal , Farh Islam Zainalabdin Abdalgadir , Mohamed Hanaa Abdalla , Elsharif Hajr Abdallha , Mohamed ALazza Abdalla Hassan , Awad-Elkareem Mawadda Abd-Elraheem , Salih Mhamed Ahmed 
Published: October 2018

AbstractIntroductionThis study aimed to design an immunogenic epitope for Cryptococcus neoformans the etiological agent of cryptococcosis using in silico simulations, for epitope prediction, we selected the mannoprotein antigen MP88 which it’s known to induce protective immunity.Material & methodA total of 39 sequences of MP88 protein with length 378 amino acids were retrieved from the National Center for Biotechnology Information database (NCBI) in the FASTA format were used to predict antigenic B-cell and T cell epitopes via different bioinformatics tools at Immune Epitope Database and Analysis Resource (IEDB). The tertiary structure prediction of MP88 was created in RaptorX, and visualized by UCSF Chimera software.ResultA Conserved B-cell epitopesAYSTPA, AYSTPAS, PASSNCK, and DSAYPPhave displayed the most promising B cell epitopes. While theYMAADQFCL, VSYEEWMNYandFQQRYTGTFthey represent the best candidates T-cell conserved epitopes, the 9-mer epitopeYMAADQFCLdisplay the greater interact with 9 MHC-I alleles and HLA-A*02:01 alleles have the best interaction with an epitope. TheVSYEEWMNYandFQQRYTGTFthey are non-allergen whileYMAADQFCLwas an allergen. For MHC class II peptide binding prediction, theYARLLSLNA, ISYGTAMAVandINQTSYARLrepresent the most Three highly binding affinity core epitopes. The core epitopeINQTSYARLwas found to interact with 14 MHC-II. The allergenicity prediction revealsISYGTAMAV, INQTSYARLwere non-allergen andYARLLSLNAwas an allergen. Regarding population coverage theYMAADQFCLexhibit, a higher percentage among the world (69.75%) and the average population coverage was93.01%.In MHC-II,ISYGTAMAVepitope reveal a higher percentage (74.39%) and the average population coverage was (81.94%). This successfully designed a peptide vaccine against Cryptococcus neoformans open up a new horizon in Cryptococcus neoformans research; the results require validation by in vitro and in vivo experiments.
Cannabichromene is a cannabinoid CB2 receptor agonist
Authors: Udoh Michael , Santiago Marina , Devenish Steven , McGregor Iain S. , Connor Mark 
Published: October 2018

BACKGROUNDCannabichromene (CBC) is one of the most abundant phytocannabinoids inCannabis spp. It has modest anti-nociceptive and anti-inflammatory effects and potentiates some effects of Δ9-tetrahydrocannabinol (THC)in vivo. How CBC exerts these effects is poorly defined and there is little information about its efficacy at cannabinoid receptors. We sought to determine the functional activity of CBC at CB1 and CB2 receptors.EXPERIMENTAL APPROACHAtT20 cells stably expressing HA-tagged human CB1 and CB2 receptors were used. Assays of cellular membrane potential and loss of cell surface receptors were performed.KEY RESULTSCBC activated CB2 but not CB1 receptors to produce a hyperpolarization of AtT20 cells. Activation of CB2 receptors was antagonised by the CB2 antagonist AM630 and sensitive to pertussis toxin. Co-application of CBC reduced activation of CB2 receptors CP55,940, a potent CB1 and CB2 agonist. Continuous CBC application induced loss of cell surface CB2 receptors and desensitisation of the CB2-induced hyperpolarization.CONCLUSIONS AND IMPLICATIONSCannabichromene is a selective CB2 receptor agonist displaying higher efficacy than THC in hyperpolarising AtT20 cells. CBC may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB2-mediated modulation of inflammation.
Defining subpopulations of differential drug response to reveal novel target populations
Authors: Keshava Nirmal , Toh Tzen S. , Yuan Haobin , Yang Bingxun , Menden Michael P. , Wang Dennis 
Published: October 2018

AbstractPersonalised medicine has predominantly focused on genetically-altered cancer genes that stratify drug responses, but there is a need to objectively evaluate differential pharmacology patterns at a subpopulation level. Here, we introduce an approach based on unsupervised machine learning to compare the pharmacological response relationships between 327 pairs of cancer therapies. This approach integrated multiple measures of response to identify subpopulations that react differently to inhibitors of the same or different targets to understand mechanisms of resistance and pathway cross-talk. MEK, BRAF, and PI3K inhibitors were shown to be effective as combination therapies for particularBRAFmutant subpopulations. A systematic analysis of preclinical data for a failed phase III trial of selumetinib combined with docetaxel in lung cancer suggests potential indications in urogenital and colorectal cancers withKRASmutation. This data-informed study exemplifies a method for stratified medicine to identify novel cancer subpopulations, their genetic biomarkers, and effective drug combinations.