bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin nanoscale compaction in live cells visualized by acceptor-donor ratio corrected FRET between DNA dyes
Authors: Pelicci Simone , Diaspro Alberto , Lanzanò Luca 
Published: June 2019

AbstractChromatin nanoscale architecture in live cells can be studied by Forster Resonance Energy Transfer (FRET) between fluorescently labeled chromatin components, such as histones. A higher degree of nanoscale compaction is detected as a higher FRET level, since this corresponds to a higher degree of proximity between donor and acceptor molecules. However, in such a system the stoichiometry of the donors and acceptors engaged in the FRET process is not well defined and, in principle, FRET variations could be caused by variations in the acceptor-donor ratio rather than distance. Here we show that a FRET value independent of the acceptor-donor ratio can be obtained by Fluorescence Lifetime Imaging (FLIM) detection of FRET combined with a normalization of the FRET level to a pixel-wise estimation of the acceptor-donor ratio. We use this method to study FRET between two DNA binding dyes staining the nuclei of live cells. We show that acceptor-donor ratio corrected FRET imaging reveals variations of nanoscale compaction in different chromatin environments. As an application, we monitor the rearrangement of chromatin in response to laser-induced micro-irradiation and reveal that DNA is rapidly decompacted, at the nanoscale, in response to DNA damage induction.
Lop-eared rabbits have more aural and dental problems than erect-eared rabbits: a rescue population study
Authors: Johnson Jade C. , Burn Charlotte C. 
Published: June 2019

AbstractThis research aimed to assess whether rabbits having lop-ears is a welfare issue by investigating the occurrence of aural and dental pathology in lop-eared compared with erect-eared rabbits.Thirty rabbits (15 lop-eared and 15 erect-eared) from a rabbit-only rescue shelter were examined. An otoscope was used to visualise the ear canals and mouth. Samples were taken from each ear to examine for mites, bacteria and yeast. Medical records were also examined.Lop-eared rabbits showed statistically significantly more frequent ear canal stenosis, higher scores of cerumen and erythema, and more frequent potential pain response during ear examination, compared with erect-eared rabbits. We also found statistically significantly more frequent incisor pathology, molar overgrowth, molar sharpness, molar spurs and history of veterinary dental treatment in lop-eared compared with erect-eared rabbits. The effect sizes were often large. Age was not statistically significant between the lop- and erect-eared rabbit groups.Thus, lop-eared rabbits are at an increased risk of aural and dental pathology. This brings into debate the ethics of breeding and buying lop-eared rabbits, as they are more likely to suffer conditions that negatively impact welfare, such as pain, and potentially deafness and difficulty eating.
Dissociating activation and integration of discourse referents: evidence from ERPs and oscillations
Authors: Coopmans Cas W. , Nieuwland Mante S. 
Published: June 2019

AbstractA key challenge in understanding stories and conversations is the comprehension of ‘anaphora’, words that refer back to previously mentioned words or concepts (‘antecedents’). In psycholinguistic theories, anaphor comprehension involves the initial activation of the antecedent and its subsequent integration into the unfolding representation of the narrated event. A recent proposal suggests that these processes draw upon the brain’s recognition memory and language networks, respectively, and may be dissociable in patterns of neural oscillatory synchronization (Nieuwland & Martin, 2017). We addressed this proposal in an electroencephalogram (EEG) study with pre-registered data acquisition and analyses, using event-related potentials (ERPs) and neural oscillations. Dutch participants read two-sentence mini stories containing proper names, which were repeated or new (ease of activation) and coherent or incoherent with the preceding discourse (ease of integration). Repeated names elicited lower N400 and Late Positive Component amplitude than new names, and also an increase in theta-band (4-7 Hz) synchronization, which was largest around 240-450 ms after name onset. Discourse-coherent proper names elicited an increase in gamma-band (60-80 Hz) synchronization compared to discourse-incoherent names. This effect was largest around 690-1000 ms after name onset and was localized to the left frontal cortex. We argue that the initial activation and subsequent discourse-level integration of referents can be dissociated with event-related EEG activity, and are associated with respectively theta- and gamma-band activity. These findings further establish the link between memory and language through neural oscillations.
Cellular contractility coordinates cytoskeletal dynamics and cell behaviour duringDrosophilaabdominal morphogenesis
Authors:   Pau Pulido Companys, Norris Anneliese , Bischoff Marcus 
Published: June 2019

AbstractDuring morphogenesis, cells undergo various behaviours, such as migration and constriction, which need to be coordinated. How this is achieved remains elusive. During morphogenesis of theDrosophilaadult abdominal epidermis, larval epithelial cells (LECs) migrate directedly before constricting apically and undergoing apoptosis. Here, we study the mechanisms underlying the transition from migration to constriction. We show that LECs possess a pulsatile apical actomyosin network and that a change in network polarity underlies behavioural change. Exploring the properties of the contractile network, we find that the level of cell contractility impacts on the network’s behaviour, as well as on overall cytoskeletal architecture and cell behaviour. We also find that pulsed contractions occur only in cells with intermediate levels of contractility. Furthermore, increasing levels of the small Rho GTPase Rho1 disrupts pulsed contractions, and instead leading to cells that cycle between two states, characterised by a junctional cortical and an apicomedial actin network. Our results highlight that behavioural change relies on tightly controlled cellular contractility. Moreover, we show that constriction can occur without pulsed contractions, raising questions about their contribution to constriction.
Optimizing Phylogenomics with Rapidly Evolving Long Exons: Comparison with Anchored Hybrid Enrichment and Ultraconserved Elements
Authors: Karin Benjamin R. , Gamble Tony , Jackman Todd R. 
Published: June 2019

AbstractMarker selection has emerged as an important component of phylogenomic study design due to rising concerns of the effects of gene tree estimation error, model misspecification, and data-type differences. Researchers must balance various trade-offs associated with locus length and evolutionary rate among other factors. The most commonly used reduced representation datasets for phylogenomics are ultraconserved elements (UCEs) and Anchored Hybrid Enrichment (AHE). Here, we introduce Rapidly Evolving Long Exon Capture (RELEC), a new set of loci that targets single exons that are both rapidly evolving (evolutionary rate faster thanRAG1) and relatively long in length (greater than 1,500 bp), while at the same time avoiding paralogy issues across amniotes. We compare the RELEC dataset to UCEs and AHE in squamate reptiles by aligning and analyzing orthologous sequences from 17 squamate genomes, composed of ten snakes and seven lizards. The RELEC dataset (179 loci) outperforms AHE and UCEs by maximizing per-locus genetic variation while maintaining presence and orthology across a range of evolutionary scales. RELEC markers show higher phylogenetic informativeness than UCE and AHE loci, and RELEC gene trees show greater similarity to the species tree than AHE or UCE gene trees. Furthermore, with fewer loci, RELEC remains computationally tractable for full Bayesian coalescent species tree analyses. We contrast RELEC to and discuss important aspects of comparable methods, and demonstrate how RELEC may be the most effective set of loci for resolving difficult nodes and rapid radiations. We provide several resources for capturing or extracting RELEC loci from other amniote groups.
Probabilistic Models of Larval Zebrafish Behavior: Structure on Many Scales
Authors: Johnson Robert Evan , Linderman Scott , Panier Thomas , Wee Caroline Lei , Song Erin , Herrera Kristian Joseph , Miller Andrew , Engert Florian 
Published: June 2019

AbstractNervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout-types emitted over time. We then construct probabilistic models – specifically, marked renewal processes – to evaluate how bout-types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.
Wide distribution of phage that infect freshwater SAR11 bacteria
Authors: Chen Lin-Xing , Zhao Yan-Lin , McMahon Katherine D. , Mori Jiro F. , Jessen Gerdhard L. , Nelson Tara Colenbrander , Warren Lesley A. , Banfield Jillian F. 
Published: June 2019

AbstractFonsibacter (LD12 subclade) are among the most abundant bacterioplankton in freshwater ecosystems. These bacteria belong to the order Pelagibacterales (SAR11) and are related to Pelagibacter (marine SAR11) that dominate many marine habitats. Although a handful of Pelagibacter phage (Pelagiphage) have been described, no phage that infect Fonsibacter have been reported. In this study, a complete Fonsibacter genome containing a prophage was reconstructed from metagenomic data. A circularized and complete genome related to the prophage, referred to as uv-Fonsiphage-EPL, shows high similarity to marine Pelagiphage HTVC025P. Additionally, we reconstructed three complete and one draft genome of phage related to marine Pelagiphage HTVC010P, and predicted a lytic strategy. The similarity in codon usage and co-occurrence patterns of HTVC010P-related phage and Fonsibacter suggested that these phage infect Fonsibacter. Similar phage were detected in Lake Mendota, Wisconsin, where Fonsibacter is also present. A search of related phage revealed the worldwide distribution of some genotypes in freshwater ecosystems, suggesting their substantial role in shaping indigenous microbial assemblages and influence on biogeochemical cycling. However, the uv-Fonsiphage-EPL and one lineage of HTVC010P-related phage have a more limited distribution in freshwater ecosystems. Based on this, and their close phylogenetic relatedness with Pelagiphage, we predict that they transitioned from saline into freshwater ecosystems comparatively recently. Overall, the findings provide insights into the genomic features of phage that infect Fonsibacter, and expand understanding of the ecology and evolution of these important bacteria.
Designing ecologically-optimised vaccines using population genomics
Authors: Colijn Caroline , Corander Jukka , Croucher Nicholas J. 
Published: June 2019

AbstractStreptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal capable of infecting normally sterile anatomical sites, resulting in invasive pneumococcal disease (IPD). Effective vaccines preventing IPD exist, but each of the antigens they contain typically induces protective immunity against only one of the approximately 100 pneumococcal serotypes, which are differentiated by immunogenically-distinct polysaccharide capsules. Serotypes vary in their propensity to cause IPD, quantified as their invasiveness. Vaccines are designed to include serotypes commonly isolated from IPD, but the immunity they induce is sufficiently strong to also eliminate vaccine serotypes from carriage. This enables their replacement by non-vaccine serotypes in the nasopharynx. The emergence of invasive non-vaccine serotypes has undermined some vaccination programmes’ benefits. Recent advances in genomics and modeling have enabled forecasting of which non-vaccine serotypes will be successful post-vaccination. Here, we demonstrate that vaccines optimised using this framework can minimise IPD and antibiotic-resistant disease more effectively than existing formulations in the model, through mitigating the consequences of serotype replacement. The simulations also demonstrate that tailoring vaccines to the pre-vaccine bacterial population is likely to have a substantial impact on reducing IPD, highlighting the importance of epidemiological data, genomics and ecological models as tools for vaccine design and evaluation.
flexiMAP: A regression-based method for discovering differential alternative polyadenylation events in standard RNA-seq data
Authors: Szkop Krzysztof J. , Moss David S. , Nobeli Irene 
Published: June 2019

AbstractSummaryWe present flexiMAP (flexible Modeling of Alternative PolyAdenylation), a new beta-regression-based method implemented in R, for discovering differential alternative polyadenylation events in standard RNA-seq data. Importantly, flexiMAP allows modeling of multiple known covariates that often confound the results of RNA-seq data analysis. We show, using simulated data, that flexiMAP is very specific and outperforms in sensitivity existing methods, especially at low fold changes. In addition, the tests on simulated data reveal some hitherto unrecognised caveats of existing methods.AvailabilityThe flexiMAP R package is available at: https://github.com/kszkop/flexiMAPScripts and data to reproduce the analysis in this paper are available at: https://doi.org/10.5281/zenodo.3238619ContactIrene Nobeli, i.nobeli@bbk.ac.uk
Nature based measures increase freshwater biodiversity in agricultural catchments
Authors: Williams Penny , Biggs Jeremy , Stoate Chris , Szczur John , Brown Colin , Bonney Simon 
Published: June 2019

AbstractThis is the first study that describes the effect of adding mitigation measures on the freshwater biodiversity of all waterbody types in agricultural catchments. We measured alpha (site) and gamma (catchment) richness annually over a nine-year period in all the streams, ponds and ditches in three upper-catchments in the English lowlands, and investigated whether freshwater plant biodiversity could be increased by adding: (i) multi-functional ecosystem services measures to intercept pollutants, store water and promote biodiversity, and, (ii) biodiversity-only protection measures. In the absence of measures, all catchments saw a decline in macrophyte richness during the survey (mean species loss of 1% pa, rare species loss of 2% pa). Ponds were a key habitat with a disproportionate influence on catchment trends. Five years after introducing measures, natural colonisation of ecosystem services waterbodies (dammed streams and ditches, runoff ponds, flood storage ponds) largely cancelled-out the background loss of plant species but, importantly, did not restore the loss of rare plants. Adding clean water ponds as a biodiversity-only enhancement measure brought substantial benefits: increasing total-catchment richness by 26%, and the number of rare plant species by 181%. Populations of spatially restricted species also increased. Adding stream debris-dams as a biodiversity measure did not affect plant richness or rarity. The findings suggest that ecosystem services measures could bring some biodiversity benefits to agricultural catchments. However, creating clean-water ponds specifically targeted for biodiversity could hold considerable potential as a tool to help stem, and even reverse, ongoing declines in freshwater plant biodiversity across farming landscapes.
Reconstruction of in-vivo subthreshold activity of single neurons from large-scale spiking recordings
Authors: Papaioannou Stylianos , Marques Smith André , Eriksson David 
Published: June 2019

SummaryCurrent developments in the manufacturing of silicon probes allow recording of spikes from large populations of neurons from several brain structures in freely moving animals. It is still, however, technically challenging to record the membrane potential from awake behaving animals. Routine access to the subthreshold activity of neurons would be of great value in order to understand the role of, for example, neuronal integration, oscillations, and excitability. Here we have developed a framework for reconstructing the subthreshold activity of single neurons using the spiking activity from large neuronal populations. The reconstruction accuracy and reliability have been evaluated with ground truth data provided from simultaneous patch clamp membrane potential recordings in-vivo. Given the abundance of large-scale spike recordings in the contemporary systems neuroscience society, this approach provides a general access to the subthreshold activity and hence could shed light on the intricate mechanisms of the genesis of spiking activity.
Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes
Authors: Dumanski Jan P. , Halvardson Jonatan , Davies Hanna , Rychlicka-Buniowska Edyta , Mattisson Jonas , Moghadam Behrooz Torabi , Nagy Noemi , Węglarczyk Kazimierz , Bukowska-Strakova Karolina , Danielsson Marcus , Olszewski Paweł , Piotrowski Arkadiusz , Oerton Erin , Ambicka Aleksandra , Przewoźnik Marcin , Bełch Łukasz , Grodzicki Tomasz , Chłosta Piotr L. , Imreh Stefan , Giedraitis Vilmantas , Kilander Lena , Nordlund Jessica , Ameur Adam , Gyllensten Ulf , Johansson Åsa , Józkowicz Alicja , Siedlar Maciej , Klich-Rączka Alicja , Jaszczyński Janusz , Enroth Stefan , Baran Jarosław , Ingelsson Martin , Perry John R. B. , Ryś Janusz , Forsberg Lars A. 
Published: June 2019

AbstractMosaic loss of chromosome Y (LOY) in leukocytes has been associated with many diseases, yet it remains unclear whether this form of clonal mosaicism exerts a direct physiological effect. Here we perform single-cell and bulk RNA sequencing in leukocytes, observing considerable variation in the rate of LOY across individuals, cell types and disease state. Cells with LOY demonstrated a profound degree of transcriptional dysregulation impacting ∼500 autosomal genes. These genes are preferentially involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y challenging the view of it as a “genetic wasteland”. Furthermore, they support the hypothesis that altered immune function in leukocytes is a mechanism directly linking LOY to disease.
Characterizing the innate and adaptive responses of immunized mice toBordetella pertussisinfection usingin vivoimaging and transcriptomic analysis
Authors: Boehm Dylan T. , Varney Melinda E. , Wong Ting Y. , Nowak Evan S. , Sen-Kilic Emel , Hall Jesse , Bradford Shelby D. , DeRoos Katherine , Bevere Justin , Epperly Matthew , Maynard Jennifer A. , Hewlett Erik L. , Barbier Mariette , Damron F. Heath 
Published: June 2019

AbstractBordetella pertussis(B. pertussis) is the causative agent of pertussis (whooping cough). Since the 1990s, pertussis has re-emerged in the United States despite an estimated 95% vaccine coverage. Our goal was to characterize neutrophil responses and gene expression profiles of murine lungs in the context of vaccination andB. pertussischallenge. We utilized a bioluminescent neutrophil mouse model (NECre luc) to track neutrophil recruitment. NECre luc mice were immunized with whole cell vaccine (WCV), acellular vaccine (ACV), or a truncated adenylate cyclase toxoid (RTX) vaccine. Neutrophil recruitment was measured in live mice across time and corroborated by flow cytometry and other data. WCV immunized mice showed signs of neutrophilia in response toB. pertussischallenge. Mice immunized with either ACV or WCV cleared the challenge infection; however immunization with RTX alone was not protective. RNA sequencing revealed distinctive gene expression profiles for each immunization group. We observed an increase in expression of genes associated with responses to infection, and changes in expression of distinct genes in each vaccine group, providing a complex view of the immune response toB. pertussisinfection in mice. This study suggests that combination of immunological analysis with transcriptomic profiling can facilitate discovery of pre-clinical correlates of protection for vaccine development.
Oligomeric state of the ZIKV E protein defines protective immune responses
Authors: Metz Stefan W. , Thomas Ashlie , Brackbill Alex , Forsberg John , Miley Michael J. , Lopez Cesar A. , Lazear Helen M. , Tian Shaomin , de Silva Aravinda M. 
Published: June 2019

AbstractThe current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies. We hypothesized that Zika Envelope (E) protein subunit vaccines have performed poorly because the antigens tested have been recombinant E monomers that do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. To test this hypothesis, we engineered and produced stable recombinant E protein homodimers. Unlike the E monomer, the dimer was recognized by strongly neutralizing monoclonal antibodies isolated from Zika-immune individuals. In a mouse model of vaccination, the dimeric antigen stimulated strongly neutralizing antibodies that targeted epitopes that were similar to epitopes recognized by human antibodies following natural Zika virus infection. In contrast, the monomer antigen stimulated lower levels of neutralizing antibodies directed to simple epitopes on domain III of E protein. In a mouse model of ZIKV challenge, only E dimer antigen stimulated protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines. The flavivirus field has a long history of using E monomers as vaccine antigens with limited success. These results are applicable to developing second generation subunit vaccines against Zika as well as other medically important flaviviruses such as dengue and yellow fever viruses.