bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competitive learning suggests circulating miRNA profiles for cancers decades prior to diagnosis
Authors: Keller Andreas , Fehlmann Tobias , Backes Christina , Kern Fabian , Gislefoss Randi , Langseth Hilde , Rounge Trine B. , Ludwig Nicole , Meese Eckart 
Published: March 2020

AbstractSmall non-coding RNAs such as microRNAs are master regulators of gene expression. One of the most promising applications of miRNAs is the use as liquid biopsy. Especially early diagnosis is an effective means to increase patients’ overall survival. E.g. in oncology a tumor is detected at best prior to its clinical manifestation. We generated genome-wide miRNA profiles from serum of patients and controls from the population-based Janus Serum Bank (JSB) and analyzed them by bioinformatics and artificial intelligence approaches. JSB contains sera from 318,628 originally healthy persons, more than 96,000 of whom later developed cancer. We selected 210 serum samples of patients with lung, colon or breast cancer at three time points prior to diagnosis, after cancer diagnosis and controls. The controls were matched with regard to age of the blood donor and to the time points of blood drawing, which were 27, 32, or 38 years prior to diagnosis. Using ANOVA we report 70 significantly deregulated markers (adjusted p-value<0.05). The driver for the significance was the diagnostic time point (miR-575, miR-6821-5p, miR-630 had adjusted p-values<10−10). Further, 91miRNAs were differently expressed in pre-diagnostic samples as compared to controls (nominal p<0.05). Unsupervised competitive learning by self-organized maps indicated larges effects in lung cancer samples while breast cancer samples showed the least pronounced changes. Self-organized maps also highlighted cancer and time point specific miRNA dys-regulation. Intriguingly, a detailed breakdown of the results highlighted that 51% of all miRNAs were highly specific, either for a time-point or a cancer entity. Our results indicate that tumors may be indicated by serum miRNAs decades prior the clinical manifestation.
Re-analysis of SARS-CoV-2 infected host cell proteomics time-course data by impact pathway analysis and network analysis. A potential link with inflammatory response
Authors: Ortea Ignacio , Bock Jens-Ole 
Published: March 2020

AbstractThe disease known as coronavirus disease 19 (COVID-19), potentially caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has hit the world hard, and has led to an unprecedent health and economic crisis. In order to develop treatment options able to stop or ameliorate SARS-CoV-2 effects, we need to understand the biology of the virus inside cells, but this kind of studies are still scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. In the present study, we use the publicly available proteomics data from this study to re-analyze the mechanisms altered by the virus infection by impact pathways analysis and network analysis. Proteins linked to inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be regulated. The up-regulation of the inflammatory-related proteins observed could be linked to the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients.
Evaluating Human Autosomal Loci for Sexually Antagonistic Viability Selection in Two Large Biobanks
Authors: Kasimatis Katja R. , Abraham Abin , Ralph Peter L. , Kern Andrew D. , Capra John A. , Phillips Patrick C. 
Published: March 2020

ABSTRACTSex and sexual differentiation are ubiquitous across the tree of life. Because females and males often have substantially different functional requirements, we expect selection to differ between the sexes. Recent studies in diverse species, including humans, suggest sexually antagonistic viability selection creates allele frequency differences between the sexes at many different loci. However, theory and population-level simulations indicate that sex-specific differences in viability would need to be very extreme in order to produce and maintain reported levels of between-sex allelic differentiation. We address this paradox between theoretical predictions and empirical observations by evaluating evidence for sexually antagonistic viability selection on autosomal loci in humans using the largest cohort to date (UK Biobank, n=438,427) along with a second large, independent cohort (BioVU, n=93,864). We performed association tests between genetically ascertained sex and genotypes. Although we found dozens of genome-wide significant associations, none replicated across samples. Moreover, closer inspection revealed that all associations are likely due to cross-hybridization with sex chromosome regions during genotyping. We report loci with potential for mis-hybridization found on commonly used genotyping platforms that should be carefully considered in future genetic studies of sex-specific differences. Despite being well-powered to detect allele frequency differences of up to 0.8% between the sexes, we do not detect evidence for this signature of sexually antagonistic viability selection on autosomal variation. These findings suggest a lack of strong ongoing sexually antagonistic viability selection acting on single locus autosomal variation in humans.
A novel setup for simultaneous two-photon functional imaging and precise spectral and spatial visual stimulation inDrosophila
Authors: Feord R. C. , Wardill T. J. 
Published: March 2020

ABSTRACTMotion vision has been extensively characterised inDrosophila melanogaster, but substantially less is known about how flies process colour, or how spectral information affects other visual modalities. To accurately dissect the components of the early visual system responsible for processing colour, we developed a versatile visual stimulation setup to probe combined spatial, temporal and spectral response properties. Using flies expressing neural activity indicators, we tracked visual responses in the medulla to a projected colour stimulus. The introduction of custom bandpass optical filters enables simultaneous two-photon imaging and visual stimulation over a large range of wavelengths without compromising the temporal stimulation rate. With monochromator-produced light, any spectral bandwidth and centre wavelength from 390 to 730 nm can be selected to produce a narrow spectral hue. A specialised screen material scatters each band of light across the visible spectrum equally at all locations of the screen, thus enabling presentation of spatially structured stimuli. We show layer-specific shifts of spectral response properties in the medulla correlating with projection regions of photoreceptor terminals.
CRISPR/Cas9 mediated mutations as a new tool for studying taste in honeybees
Authors: Değirmenci Laura , Geiger Dietmar , Rogé Ferreira Fábio Luiz , Keller Alexander , Krischke Beate , Beye Martin , Steffan-Dewenter Ingolf , Scheiner Ricarda 
Published: March 2020

AbstractBackgroundHoneybees rely on nectar as their main source of carbohydrates [1]. Sucrose, glucose and fructose are the main components of plant nectars [2] [3]. Intriguingly, honeybees express only three putative sugar receptors (AmGr1, AmGr2 and AmGr3) [4], which is in stark contrast to many other insects and vertebrates. The sugar receptors are only partially characterized [5] [6]. AmGr1 detects different sugars including sucrose and glucose. AmGr2 is assumed to act as a co-receptor only, while AmGr3 is assumedly a fructose receptor.ResultsWe show that honeybee gustatory receptor AmGr3 is highly specialized for fructose perception when expressed inXenopusoocytes. When we introduced nonsense mutations to the respectiveAmGr3gene using CRISPR/Cas9 in eggs of female workers, the resulting mutants displayed almost a complete loss of responsiveness to fructose. In contrast, responses to sucrose were normal. Nonsense mutations introduced by CRISPR/Cas9 in honeybees can thus induce a measurable behavioural change and serve to characterize the function of taste receptorsin vivo.ConclusionCRISPR/Cas9 is an excellent novel tool for characterizing honeybee taste receptorsin vivo. Biophysical receptor characterisation inXenopusoocytes and nonsense mutation ofAmGr3in honeybees unequivocally demonstrate that this receptor is highly specific for fructose.Graphical AbstractFigure 0
Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses
Authors: da Costa Kelli Monteiro , Salustiano Eduardo J. , do Carmo Valente Raphael , Freire-de-Lima Leonardo , Mendonça-Previato Lucia , Previato José Osvaldo 
Published: March 2020

AbstractThe protozoanTrypanosoma cruziis the etiologic agent for Chagas disease, which affects 6-7 million people worldwide. The parasite presents high biological diversity, reflecting on the inefficiency of benznidazole in chronic or older patients. ABC superfamily proteins contain active transporters involved in the xenobiotic and endobiotic efflux and overexpressed in MDR cells. An ABCC-like transport was identified in theT. cruziY strain, being able to extrude thiol-conjugated compounds. As non-protein thiols represent prime line of defense towards reactive species, ABCC-like activity could participate in the regulation of mediators implicated in responses to cellular stress arising from a variety of stimuli, as environmental or chemotherapeutic. This study shows thatT. cruziABCC-like protein transports GSH, GSSG and ceramides, all implicated in cellular stress. Hemin, representative from the hematophagous feeding of the vector, was transported as well, suggesting a role for ABCC as a metal-thiol transporter. In addition, all strains evaluated showed ABCC-like activity, while no ABCB1-like activity was detected. Also, results suggest that ABCC-like does not associate to natural resistance to benznidazole, considering that the sensitive strains CL Brener and Berenice showed higher ABCC-like activity than the resistant strains Y and Colombiana. Instead, ABCC-like efflux increased after continuous exposure of Y strain to benznidazole. Moreover, ABCC does not perform direct efflux of drug and its participation in the machinery of protection against stress depends on the efflux of metabolites in conjugation to or in cotransport with thiol.
Structural basis for the complex DNA binding behavior of the plant stem cell regulator WUSCHEL
Authors: Sloan Jeremy , Hakenjos Jana P. , Gebert Michael , Ermakova Olga , Gumiero Andrea , Stier Gunter , Wild Klemens , Sinning Irmgard , Lohmann Jan U. 
Published: March 2020

AbstractStem cells are one of the foundational evolutionary novelties that allowed the independent emergence of multicellularity in the plant and animal lineages. In plants, the homeodomain (HD) transcription factor WUSCHEL (WUS) is essential for the maintenance of stem cells in the shoot apical meristem. WUS has been reported to bind to diverse DNA motifs and to act as transcriptional activator and repressor. However, the mechanisms underlying this remarkable behavior have remained unclear. Here, we quantitatively delineate WUS binding to three divergent DNA motifs and resolve the relevant structural underpinnings. We show that WUS exhibits a strong binding preference for TGAA repeat sequences, while retaining the ability to weakly bind to TAAT elements. This behavior is attributable the formation of dimers through interactions of specific residues in the HD that stabilize WUS DNA interaction. Our results provide a mechanistic basis for dissecting WUS dependent regulatory networks in plant stem cell control.
Developmental atlas of white lupin cluster roots
Authors: Gallardo Cécilia , Hufnagel Bárbara , Soriano Alexandre , Divol Fanchon , Marquès Laurence , Doumas Patrick , Péret Benjamin 
Published: March 2020

AbstractDuring the course of evolution, plants have developed various strategies to improve micronutrient acquisition, such as cluster roots. These spectacular structures are dedicated to efficient phosphate remobilization and acquisition. When exposed to Pi-limitation, white lupin forms cluster roots made of dense clusters of short specialized roots, called rootlets. Although the physiological activity of rootlets has been well studied, their development remains poorly described. Here, we provide a developmental atlas of white lupin early rootlet development, using molecular markers derived from the model plant Arabidopsis. We first focused on cell division patterns to determine which cells contribute to the rootlet primordium. Then, we identified homologs of previously described tissue specific genes based on protein sequence analysis and also using detailed transcriptomic data covering rootlet development. This study provides a comprehensive description of the developmental phases of rootlet formation, highlighting that rootlet primordium arises from divisions in pericycle, endodermis and cortex. We describe that rootlet primordium patterning follows eight stages during which tissue differentiation is established progressively.HighlightWhite lupin cluster roots consist in the formation of numerous rootlets whose development can be divided in 8 stages and involves divisions in the pericycle, endodermis and cortex.
Non-invasive surveys of mammalian viruses using environmental DNA
Authors: Alfano Niccolò , Dayaram Anisha , Axtner Jan , Tsangaras Kyriakos , Kampmann Marie-Louise , Mohamed Azlan , Wong Seth T. , Gilbert M. Thomas P. , Wilting Andreas , Greenwood Alex D. 
Published: March 2020

ABSTRACTEnvironmental DNA (eDNA) and invertebrate-derived DNA (iDNA) have been used to survey biodiversity non-invasively to mitigate difficulties of obtaining wildlife samples, particularly in remote areas or for rare species. Recently, eDNA/iDNA have been applied to monitor known wildlife pathogens, however, most wildlife pathogens are unknown and often evolutionarily divergent.To detect and identify known and novel mammalian viruses from eDNA/iDNA sources, we used a curated set of RNA oligonucleotides as viral baits in a hybridization capture system coupled with high throughput sequencing.We detected multiple known and novel mammalian RNA and DNA viruses from multiple viral families from both waterhole eDNA and leech derived iDNA. Congruence was found between detected hosts and viruses identified in leeches and waterholes.Our results demonstrate that eDNA/iDNA samples represent an effective non-invasive resource for studying wildlife viral diversity and for detecting novel potentially zoonotic viruses prior to their emergence.
Anticipatory responses along motion trajectories in awake monkey area V1
Authors: Benvenuti Giacomo , Chemla Sandrine , Boonman Arjan , Perrinet Laurent , Masson Guillaume S , Chavane Frédéric 
Published: March 2020

ABSTRACTWhat are the neural mechanisms underlying motion integration of translating objects? Visual motion integration is generally conceived of as a feedforward, hierarchical, information processing. However, feedforward models fail to account for many contextual effects revealed using natural moving stimuli. In particular, a translating object evokes a sequence of transient feedforward responses in the primary visual cortex but also propagations of activity through horizontal and feedback pathways. We investigated how these pathways shape the representation of a translating bar in monkey V1. We show that, for long trajectories, spiking activity builds-up hundreds of milliseconds before the bar enters the neurons’ receptive fields. Using VSDI and LFP recordings guided by a phenomenological model of propagation dynamics, we demonstrate that this anticipatory response arises from the interplay between horizontal and feedback networks driving V1 neurons well ahead of their feedforward inputs. This mechanism could subtend several perceptual contextual effects observed with translating objects.HighlightsOur hypothesis is that lateral propagation of activity in V1 contributes to the integration of translating stimuliConsistent with this hypothesis, we find that a translating bar induces anticipatory spiking activity in V1 neurons.A V1 model describes how this anticipation can arise from inter and intra-cortical lateral propagation of activity.The dynamic of VSDi and LFP signals in V1 is consistent with the predictions made by the model.The intra-cortical origin is further confirmed by the fact that a bar moving from the ipsilateral hemifield does not evoke anticipation.Horizontal and feedback input are not only modulatory but can also drive spiking responses in specific contexts.
FLOWERING LOCUS T4 (HvFT4)delays flowering and decreases floret fertility in barley
Authors: Pieper Rebecca , Tomé Filipa , von Korff Maria 
Published: March 2020

AbstractFLOWERING LOCUS T-like genes (FT-like) control the photoperiodic regulation of flowering in many angiosperm plants. The family ofFT-like genes is characterised by extensive gene duplication and subsequent diversification ofFTfunctions which occurred independently in modern angiosperm lineages. In barley, there are 12 knownFT-like genes (HvFT) but the function of most of them remains uncharacterised. This study aimed to characterise the role of HvFT4 in flowering time control and development in barley. The overexpression ofHvFT4in the spring cultivar Golden Promise delayed flowering time under long-day conditions. Microscopic dissection of the shoot apical meristem (SAM) revealed that overexpression ofHvFT4specifically delayed spikelet initiation and reduced the number of spikelet primordia and grains per spike. Furthermore, ectopic overexpression ofHvFT4was associated with floret abortion and with the downregulation of the barley MADS-box genesVRN-H1, HvBM3andHvBM8which promote floral development. This suggests that HvFT4 functions as a repressor of reproductive development in barley. Unraveling the genetic basis ofFT-like genes can contribute to the identification of novel breeding targets to modify reproductive development and thereby spike morphology and grain yield.HighlightWe identify theFLOWERING LOCUS T(FT)-like geneHvFT4as a negative regulator of reproductive development, spikelet initiation, floret fertility and grain number in barley.
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies
Authors: Wrapp Daniel , De Vlieger Dorien , Corbett Kizzmekia S. , Torres Gretel M. , Van Breedam Wander , Roose Kenny , van Schie Loes ,   VIB-CMB COVID-19 Response Team, Hoffmann Markus , Pöhlmann Stefan , Graham Barney S. , Callewaert Nico , Schepens Bert , Saelens Xavier , McLellan Jason S. 
Published: March 2020

ABSTRACTThe pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV-1) and COVID-19 coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.
Ppd-H1integrates drought stress signals to control spike development and flowering time in barley
Authors: Gol Leonard , Haraldsson Einar B. , von Korff Maria 
Published: March 2020

AbstractDrought impairs growth and spike development and is therefore a major cause of yield losses in the temperate cereals barley and wheat. Here, we show that the photoperiod response genePHOTOPERIOD-H1(Ppd-H1) interacts with drought stress signals to modulate spike development. We tested the effects of a continuous mild and a transient severe drought stress on developmental timing and spike development in spring barley cultivars with a natural mutation inppd-H1and derived introgression lines carrying the wild-typePpd-H1allele from wild barley. Mild drought reduced the spikelet number and delayed floral development in spring cultivars but not the introgression lines with a wild-typePpd-H1allele. Similarly, drought-triggered reductions in plant height, tiller and spike number were more pronounced in the parental lines compared to the introgression lines. Transient severe stress halted growth and floral development, upon rewatering introgression lines, but not the spring cultivars, accelerated development so that control and stressed plants flowered almost simultaneously. These genetic differences in development were correlated with a differential downregulation of the flowering promotorsFLOWERING LOCUS T1and the BARLEY MADS-box genesBM3andBM8.Our findings, therefore, demonstrate thatPpd-H1affects developmental plasticity in response to drought in barley.HighlightWe show thatPpd-H1integrates photoperiod and drought stress signals viaFLOWERING LOCUS T1 (FT1)and the downstream MADS-box genesBM3andBM8to modulate reproductive development, and shoot and spike morphology in barley.
Shared and distinct patterns of atypical cortical morphometry in children with autism and anxiety
Authors: Yin Shelly , Hong Seok-Jun , Di Martino Adriana , Milham Michael P. , Park Bo-Yong , Benkarim Oualid , Bethlehem Richard A.I. , Bernhardt Boris C. , Paquola Casey 
Published: March 2020

ABSTRACTAutism spectrum disorder (ASD) and anxiety disorders (ANX) are common neurodevelopmental conditions with several overlapping symptoms. Notably, many children and adolescents with ASD also have an ANX diagnosis, suggesting shared pathological mechanisms. Here, we leveraged structural imaging and phenotypic data from 82 closely matched children (28 ASD, 28 ANX, 26 typically developing controls). Our neuroimaging paradigm assessed cortical thickness and studied inter-regional structural covariance networks. Both ASD and ANX presented with atypical structural network organization relative to controls. Specifically, ASD presented with increased thickness in temporal and parietal midline cortices, while ANX was associated with increased cortical thickness in the left inferior frontal and precentral gyri. Despite the overall difference in the spatial distributions these clusters, unconstrained spin permutation testing showed that statistical maps from the ANX-vs-controls and ASD-vs-controls analyses were significantly correlated. The two diagnostic groups also presented with common decreases in structural covariance patterns, collectively pointing to decreased structural coupling between lateral frontal, lateral temporal, and temporo-parietal regions. Dimensional analysis of trait anxiety and social responsiveness partially recapitulated diagnosis-based findings. Collectively, our findings provide evidence for both shared as well as distinct effects of ASD and ANX on on regional and inter-regional structural network organization.