bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male and female bees show large differences in floral preference
Authors: Roswell Michael , Dushoff Jonathan , Winfree Rachael 
Published: October 2018

AbstractIntraspecific variation in foraging niche can drive food web dynamics and ecosystem processes. Field studies and theoretical analysis of plant-pollinator interaction networks typically focus on the partitioning of the floral community between pollinator species, with little attention paid to intraspecific variation among plants or foraging bees. In other systems, male and female animals exhibit different, cascading, impacts on interaction partners. Although the foraging ecology of male bees is little known, we expect foraging preferences to differ between male and female bees, which could strongly impact plant-pollinator interaction outcomes.We designed an observational study to evaluate the strength and prevalence of sexually dimorphic foraging preferences in bees.We observed bees visiting flowers in semi-natural meadows in New Jersey, USA. To detect differences in flower use against a shared background resource availability, we maximized the number of interactions observed within narrow spatio-temporal windows. To distinguish observed differences in bee use of flower species, which can reflect abundance patterns and sampling effects, from underlying differences in bee preferences, we analyzed our data with both a permutation-based null model and random effects models.We found that the diets of male and female bees of the same species were often as dissimilar as the diets of bees of different species. Furthermore, we demonstrate differences in preference between male and female bees, and identify plant species that are particularly attractive to each sex. We show that intraspecific differences in preference can be robustly identified within interactions between hundreds of species, without precisely quantifying resource availability, and despite high phenological turnover.Given the large differences in flower use and preference between male and female bees, ecological sex differences should be integrated into studies of bee demography, plant pollination, and coevolutionary relationships between flowers and insects.
High-level correction of the sickle mutation amplified in vivo during erythroid differentiation
Authors: Magis Wendy , DeWitt Mark A. , Wyman Stacia K. , Vu Jonathan T. , Heo Seok-Jin , Shao Shirley J , Hennig Fiona , Romero Zulema G. , Campo-Fernandez Beatriz , McNeill Matthew , Rettig Garrett R. , Sun Yongming , Lau Patrick J. , Wang Yu , Behlke Mark A. , Kohn Donald B. , Boffelli Dario , Walters Mark C. , Corn Jacob E. , Martin David I.K. 
Published: October 2018

ABSTRACTSickle Cell Disease (SCD), one of the world’s most common genetic disorders, causes anemia and progressive multiorgan damage that typically shortens lifespan by decades; currently there is no broadly applicable curative therapy. Here we show that Cas9 RNP-mediated gene editing with an ssDNA oligonucleotide donor yields markerless correction of the sickle mutation in more than 30% of long-term engrafting human hematopoietic stem cells (HSCs), using a selection-free protocol that is directly applicable to a clinical setting. We further find that in vivo erythroid differentiation markedly enriches for corrected ß-globin alleles. Adoption of a high-fidelity Cas9 variant demonstrates that this approach can yield efficient editing with almost no off-target events. These findings indicate that the sickle mutation can be corrected in human HSCs at curative levels with a streamlined protocol that is ready to be translated into a therapy.ONE SENTENCE SUMMARYCas9-mediated correction of the sickle mutation in human hematopoietic stem cells can be accomplished at curative levels.
The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair
Authors: Guard Steven E. , Poss Zachary C. , Ebmeier Christopher C. , Pagratis Maria , Taatjes Dylan J. , Old William M. 
Published: October 2018

AbstractLoss of function mutations in the protein kinase DYRK1A lead to a syndromic form of autism spectrum disorder and intellectual disability. Conversely, increased DYRK1A dosage is implicated in atypical brain development and neurocognitive deficits in trisomy 21. DYRK1A regulates a diverse array of cellular processes through kinase dependent and independent interactions with substrates and binding partners. Recent evidence implicates DYRK1A in direct regulation of the transcriptional machinery, but many of the molecular details are not yet known. Furthermore, the landscape of DYRK1A interactions in the nucleus is incomplete, impeding progress toward understanding its function in transcription. Here, we used immunoaffinity purification and mass spectrometry to identify nuclear interaction partners of endogenous DYRK1A. These were enriched in DNA damage repair factors, transcriptional elongation factors and E3 ubiquitin ligases. We validated an interaction with RNF169, a factor that promotes homology directed repair upon DNA damage. We further show that knockout of DYRK1A or treatment with DYRK1A inhibitors in HeLa cells impaired efficient recruitment of 53BP1 to DNA double strand breaks induced by ionizing radiation. This nuclear interactome thus reveals a new role for DYRK1A in DNA damage repair and provides a resource for exploring new functions of DYRK1A in the nucleus.
Herbarium records reveal early flowering in response to warming in the southern hemisphere
Authors: Daru Barnabas H. , Kling Matthew M. , Meineke Emily K. , van Wyk Abraham E. 
Published: October 2018

AbstractPremise of the StudyHerbarium specimens are increasingly used as records of plant flowering phenology, which has advanced for many species in response to climate change. However, most herbarium-based studies on plant phenology focus on taxa from temperate parts of the northern hemisphere. Here, we explore flowering phenologic responses to climate in a temperate/subtropical plant genus Protea (Proteaceae), an iconic group of woody plants with year-round flowering phenology and endemic to sub-Saharan Africa. Protea is widely used in horticulture and is a flagship genus for the flora of the hyperdiverse Cape Floristic Region.MethodsWe used a database of 2154 herbarium records of 25 Protea species to explore patterns in flowering spanning the past 100 years. We used a circular sliding window analysis to characterize phenological patterns in these aseasonal species, plus a novel linear mixed effects model formulation to test how both site-to-site and year-to-year variation in temperature and precipitation affect flowering date across species.ResultsBoth warmer sites and warmer years were associated with earlier flowering of 3–5 days/°C. In general, the timing of peak flowering was influenced more strongly by temperature than precipitation. Although species vary widely in when they flower during the year, their phenological responses to temperature are phylogenetically conserved, with closely related species tending to shift flowering time similarly with increasing temperature.DiscussionTogether, our results point to climate-responsive phenology for this important plant genus. Our results indicate that the subtropical, aseasonally-flowering genus Protea has temperature-driven flowering phenologic responses that are remarkably similar in magnitude to those of better-studied northern temperate plant species, suggesting a generality across biomes that has not been described elsewhere.
USP15 participates in HCV propagation through the regulation of viral RNA translation and lipid droplet formation
Authors: Kusakabe Shinji , Suzuki Tatsuya , Sugiyama Yukari , Haga Saori , Horike Kanako , Tokunaga Makoto , Hirano Junki , He Zhang , Chen David Virya , Ishiga Hanako , Komoda Yasumasa , Ono Chikako , Fukuhara Takasuke , Yamamoto Masahiro , Ikawa Masahito , Satoh Takashi , Akira Shizuo , Tanaka Tomohisa , Moriishi Kohji , Fukai Moto , Taketomi Akinobu , Yoshio Sachiyo , Kanto Tatsuya , Suzuki Tetsuro , Okamoto Toru , Matsuura Yoshiharu 
Published: October 2018

AbstractHepatitis C virus (HCV) utilizes cellular factors for an efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of de-ubiquitinating enzymes (DUBs) or overexpression of non-specific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up an RNAi screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR122 cells) but not in a non-hepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responsesin vitroandin vivo. We also found that USP15-deficient Huh7 cells showed reductions in the sizes and numbers of lipid droplets (LDs), and addition of palmitic acids restored the production of infectious HCV particles. Taken together, these data suggest that USP15 participates in HCV propagation by regulating the translation of HCV RNA and formation of LDs.
Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus
Authors: Luo Xiao , Guet-McCreight Alexandre , Villette Vincent , Francavilla Ruggiero , Marino Beatrice , Chamberland Simon , Skinner Frances K , Topolnik Lisa 
Published: October 2018

SUMMARYIn the hippocampus, a highly specialized population of vasoactive intestinal peptide (VIP)-expressing interneuron-specific (IS) inhibitory cells provides local circuit disinhibition via preferential innervation of different types of GABAergic interneurons. While disinhibition can be critical in modulating network activity and different forms of hippocampal learning, the synaptic and integrative properties of IS cells and their recruitment during network oscillations remain unknown. Using a combination of patch-clamp recordings, photostimulation, computational modelling as well as recordings of network oscillations simultaneously with two-photon Ca2+-imaging in awake mice in vivo, we identified synaptic mechanisms that can control the firing of IS cells, and explored their impact on the cell recruitment during theta oscillations and sharp-wave-associated ripples. We found that IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, integrating their intrinsic and synaptic properties into computational models predicted recruitment of these cells during the rising to peak phases of theta oscillations and during ripples depending on inhibitory contributions. In vivo Ca2+-imaging in awake mice confirmed in part the theoretical predictions, revealing a significant speed modulation of IS cells and their preferential albeit delayed recruitment during theta-run epochs, with firing at the rising phase to peak of the theta cycle. However, it also uncovered that IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.
GWAS-driven Pathway Analyses and Functional Validation Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse
Authors: Yu Mengyao , Georges Adrien , Tucker Nathan R. , Kyryachenko Sergiy , Toomer Katelyn , Schott Jean-Jacques , Delling Francesca N. , Ellinor Patrick T. , Levine Robert A. , Slaugenhaupt Susan A. , Hagège Albert A. , Dina Christian , Jeunemaitre Xavier , Milan David J. , Norris Russell A. , Bouatia-Naji Nabila 
Published: October 2018

AbstractNonsyndromic Mitral valve prolapse (MVP) is a common degenerative valvular heart disease with severe health consequences, including arrhythmia, heart failure and sudden death. MVP is characterized by excess extracellular matrix secretion and cellular disorganization which leads to bulky valves that are unable to co-apt properly during ventricular systole. However, the triggering mechanisms of this process are mostly unknown. Using pathway enrichment tools applied to GWAS we show that genes at risk loci are involved in biological functions relevant to cell adhesion and migration during cardiac development and in response to shear stress. Through genetic, in silico and in vivo experiments we demonstrates the presence of several genes involved in gene regulation, including GLIS1, a transcription factor that regulates Hedgehog signaling. Our findings define genetic, molecular and cellular mechanisms underlying non-syndromic MVP and implicate disrupted endothelial to mesenchymal transition and cell migration as a potential common cause to this disease.
A post-decisional neural marker of confidence predicts information-seeking in decision-making
Authors: Desender Kobe , Murphy Peter , Boldt Annika , Verguts Tom , Yeung Nick 
Published: October 2018

AbstractTheoretical work predicts that decisions made with low confidence should lead to increased information-seeking. This is an adaptive strategy because it can increase the quality of a decision, and previous behavioral work has shown that decision-makers engage in such confidence-driven information seeking. The present study aimed to characterize the neural markers that mediate the relationship between confidence and information-seeking. A paradigm was used in which human participants made an initial perceptual decision, and then decided whether or not they wanted to sample more evidence before committing to a final decision and confidence judgment. Pre-decisional and post-decisional ERP components were similarly modulated by the level of confidence and by information-seeking choices. Time-resolved multivariate decoding of scalp EEG signals first revealed that information-seeking choices could be decoded from the time of the initial decision to the time of the subsequent information-seeking choice (within-condition decoding). No above-chance decoding was visible in the pre-response time window. Crucially, a classifier trained to decode high versus low confidence predicted information-seeking choices after the initial perceptual decision (across-condition decoding). This time window corresponds to that of a post-decisional neural marker of confidence. Collectively, our findings demonstrate for the first time that neural indices of confidence are functionally involved in information-seeking decisions.
Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis
Authors: Barahona-Corrêa J. Bernardo , Cotovio Gonçalo , Costa Rui M. , Ribeiro Ricardo , Velosa Ana , Silva Vera Cruz e , Sperber Christoph , Karnath Hans-Otto , Senova Suhan , Oliveira-Maia Albino J. 
Published: October 2018

ABSTRACTBackgroundDespite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated.AimsTo test whether focal brain lesions in lesional mania are more often right-than left-sided, and if lesions converge on areas relevant to mood regulation.MethodsWe performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflected diagnoses and structures of interest, and lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, to select reports of adult-onset hypomania, mania or mixed state following a focal brain lesion. When available, eligible lesion images were manually traced onto the corresponding slices of MNI space, and lesion topography analyzed using standard brain atlases. Pooled-analyses of individual patient data were performed.ResultsData from 207 lesional mania patients was extracted from 110 reports. Among patients with focal lesions (N=197) more patients had lesions involving the right (84.3%) than the left (34.5%) hemisphere. Among 54 lesion images that were available, right-sided predominance of lesions was confirmed, and found to be was conserved across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, in addition to several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions.ConclusionsPooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.
Identifying novel subtypes of irritability using a developmental genetic approach
Authors: Riglin Lucy , Eyre Olga , Thapar Ajay K , Stringaris Argyris , Leibenluft Ellen , Pine Daniel , Tilling Kate , Smith George Davey , O’Donovan Michael C , Thapar Anita 
Published: October 2018

AbstractObjectiveIrritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study used a developmental approach to test the hypothesis that there are several forms of irritability, including a ‘neurodevelopmental/ADHD-like’ subtype with onset in childhood and a ‘depression/mood’ subtype with onset in adolescence.MethodData were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatric diagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk was indexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) derived using large genome-wide association study results.ResultsFive irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45–204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09–1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent MDD (OR=5.14 (2.47–10.73), p<0.001) and MDD PRS (OR=1.20, (1.05–1.38), p=0.009). Both trajectory classes were associated with MDD diagnosis and ADHD genetic risk.ConclusionsThe developmental context of irritability may be important in its conceptualization: early-onset persistent irritability maybe more ‘neurodevelopmental/ADHD-like’ and later-onset irritability more ‘depression/mood-like’. This has implications for treatment as well as nosology.
RNA polymerase I transcription fidelity, speed and processivity depend on the interplay of its lobe binding subunits
Authors: Merkl Philipp E. , Pilsl Michael , Fremter Tobias , Längst Gernot , Milkereit Philipp , Griesenbeck Joachim , Tschochner Herbert 
Published: October 2018

AbstractEukaryotic RNA polymerases I and III (Pol I and III) consist of core subunits, which are conserved in RNA polymerase II (Pol II). Additionally, Pol I and III have specific subunits, associating with the so-called ‘lobe’ structure first described within Pol II. In Pol I of the yeastS. cerevisiae, these are Rpa34.5, and the N-terminal domains of Rpa49 and Rpa12.2, here referred to as the lobe-binding module (lb-module). We analyzed functions of the lb-module in a definedin vitrotranscription system. Cooperation between lb-module components influenced transcription fidelity, elongation speed, and release of stalled Pol I complexes to continue elongation. Interestingly, lb-module containing Pol I and III, but not Pol II, were able to transcribe nucleosomal templates. Our data suggest, how the Pol I specific subunits may contribute to accurate and processive transcription of ribosomal RNA genes.
Mathematical modelling of serine integrase - mediated gene assembly
Authors: Pokhilko Alexandra , Kane Steven , Stark W. Marshall , Colloms Sean D. 
Published: October 2018

AbstractSite-specific recombination promoted by serine integrases can be used for ordered assembly of DNA fragments into larger arrays. When a plasmid vector is included in the assembly, the circular product DNA molecules can transformE. colicells. A convenient “one-pot” method using a single integrase involves recombination between pairs of matched orthogonal attachment sites, allowing assembly of up to six DNA fragments. However, the efficiency of assembly decreases as the number of fragments increases, due to accumulation of incorrect products in which recombination has occurred between mismatched sites. Here we use mathematical modelling to analyse published experimental data for the assembly reactions and suggest potential ways to improve assembly efficiency. We assume that unproductive synaptic complexes between pairs of mismatched sites become predominant as the number and diversity of sites increase. Our modelling predicts that the proportion of correct products can be improved by raising fragment DNA concentrations and lowering plasmid vector concentration. The assembly kinetics is affected by the inactivation of integrasein vitro. The model also predicts that the precision might be improved by redesigning the location of attachment sites on fragments to reduce the formation of the wrong circular products. Our preliminary experimental explorations of assembly with ϕC31 integrase confirmed that assembly efficiency might be improved. However, optimization of efficiency would require more experimental work on the mechanisms of wrong product formation. The use of a more efficient integrase (such as Bxb1) might be a more promising approach to assembly optimization. The model might be easily extended for different integrases or/and different assembly strategies, such as those using multiple integrases or multiple substrate structures.
Discrete stepping and nonlinear ramping dynamics underlie spiking responses of LIP neurons during decision-making
Authors: Zoltowski David M. , Latimer Kenneth W. , Yates Jacob L. , Huk Alexander C. , Pillow Jonathan W. 
Published: October 2018

AbstractNeurons in macaque area LIP exhibit gradual ramping in their trial-averaged spike responses during sensory decision-making. However, recent work has sparked debate over whether single-trial LIP spike trains are better described by discrete “stepping” or continuous drift-diffusion (“ramping”) dynamics. Here we address this controversy using powerful model-based analyses of LIP spike responses. We extended latent dynamical models of LIP spike trains to incorporate non-Poisson spiking, baseline firing rates, and various nonlinear relationships between the latent variable and firing rate. Moreover, we used advanced model-comparison methods, including cross-validation and a fully Bayesian information criterion, to evaluate and compare models. These analyses revealed that when non-Poisson spiking was incorporated into existing stepping and ramping models, a majority of neurons remained better described by stepping dynamics, even when conditioning on evidence level or choice. However, an extended ramping model with a non-zero baseline and a compressive output nonlinearity accounted for roughly as many neurons as the stepping model. The latent dynamics inferred under this model exhibited high diffusion variance for many neurons, making them qualitatively different than slowly-evolving continuous dynamics. These findings generalized to alternative tasks, suggesting that a robust fraction of LIP neurons are better described by each model class.