bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of non-invasive brain stimulation on visual perspective taking: A meta-analytic study
Authors: Yao Yuan-Wei , Chopurian Vivien , Zhang Lei , Lamm Claus , Heekeren Hauke R. 
Published: April 2021

AbstractVisual perspective taking (VPT) is a critical ability required by complex social interaction. Non-invasive brain stimulation (NIBS) has been increasingly used to examine the causal relationship between brain activity and VPT, yet with heterogeneous results. In the current study, we conducted two meta-analyses to examine the effects of NIBS of the right temporoparietal junction (rTPJ) or dorsomedial prefrontal cortex (dmPFC) on VPT, respectively. We performed a comprehensive literature search to identify qualified studies, and computed the standardized effect size (ES) for each combination of VPT level (Level-1: visibility judgment; Level-2: mental rotation) and perspective (self and other). Thirteen studies (rTPJ: 12 studies, 23 ESs; dmPFC: 4 studies, 14 ESs) were included in the meta-analyses. Random-effects models were used to generate the overall effects. Subgroup analyses for distinct VPT conditions were also performed. We found that rTPJ stimulation significantly improved participants’ visibility judgment from the allocentric perspective, whereas its effects on other VPT conditions are negligible. Stimulation of dmPFC appeared to influence Level-1 performance from the egocentric perspective, although it was only based on a small number of studies. Notably, contrary to some theoretical models, we did not find strong evidence that these regions are involved in Level-2 VPT with a higher requirement of mental rotation. These findings not only advanced our understanding of the causal roles of the rTPJ and dmPFC in VPT, but also revealed the efficacy of NIBS on VPT is relatively small. Researchers should also be cautious about the potential publication bias and selective reporting.
A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques
Authors: Harris Paul E. , Brasel Trevor , Massey Christopher , Herst C. V. , Burkholz Scott , Lloyd Peter , Blankenberg Tikoes , Bey Thomas M. , Carback Richard , Hodge Thomas , Ciotlos Serban , Wang Lu , Comer Jason E. , Rubsamen Reid 
Published: April 2021

AbstractBackgroundPersistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.MethodsUsing a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108TCID50units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.ResultsVaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.ConclusionsWe demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.Graphical Abstract
Mountain radiations are not only rapid and recent: Ancient diversification of South American frog and lizard families related to Paleogene Andean orogeny and Cenozoic climate variations
Authors: Boschman Lydian M. , Condamine Fabien L. 
Published: April 2021

AbstractMountainous areas host a disproportionately large fraction of Earth’s biodiversity, suggesting a causal relationship between mountain building and biological diversification. Mountain clade radiations are generally associated with changes in environment, climate, and the increase in heterogeneity therein during mountain building. However, examining the causal relationship between mountain building and diversification is a complex challenge, because isolating the effects of surface uplift from other abiotic (climate) or biotic variables is not straightforward. In this study, we investigate the relative contributions of abiotic climate-driven (temperature) and geology-driven (elevation) drivers on evolutionary rates of ancient groups of organisms in the South American Andes. We present regional curves of Andean elevation based on a recent compilation of paleo-elevational data back to the Late Cretaceous, and analyse the diversification history of six Andean frog and lizard families that originated equally far back in time. For two clades (Aromobatidae and Leptodactylidae), we find that they diversified most rapidly during the early phase of mountain building (Late Cretaceous - Paleogene), when the first high-elevation habitats emerged in South America. The diversification of one clade (Centrolenidae) is correlated with Cenozoic temperature variations, with higher speciation rates during warm periods. The last three clades (Dendrobatidae, Hemiphractidae and Liolaemidae) are best explained by environment-independent diversification, although for Liolaemidae, an almost equally strong positive correlation was found between speciation and Andean elevation since the late Eocene. Our findings imply that throughout the long-lived history of surface uplift in the Andes, mountain building drove the diversification of different clades at different times, while not directly affecting other clades. Our study illustrates the importance of paleogeographic reconstructions that capture the complexity and heterogeneity of mountain building in our understanding of the effects that a changing environment plays in shaping biodiversity patterns observed today.HighlightsWe provide novel regional paleoelevation curves for the Andes back to the Late CretaceousThe diversification history of six Andean-centered clades is studiedWe find clade-specific responses to environmental changesThe impact of Andean uplift could reach further back in time than previously thought
Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis
Authors: Li Xiaodong , Gordon Patrick J. , Gaynes John A. , Fuller Alexandra W. , Ringuette Randy , Santiago Clayton P. , Wallace Valerie A. , Blackshaw Seth , Li Pulin , Levine Edward M. 
Published: April 2021

AbstractAn important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcriptional regulation of signaling components or accessory factors. We previously showed that during optic vesicle patterning, the Lim-homeodomain transcription factor Lhx2 has a contextual role by linking the Sonic Hedgehog (Shh) pathway to downstream targets without regulating the pathway itself. Here, we show that during early retinal neurogenesis, Lhx2 is a multilevel regulator of Shh signaling. Specifically, Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of signaling in retinal progenitor cells. The Shh co-receptors Cdon and Gas1 are candidate direct targets of Lhx2 that mediate pathway activation, whereas Lhx2 directly or indirectly promotes the expression of other pathway components important for activation and sustained signaling. We also provide genetic evidence suggesting that Lhx2 has a contextual role by linking the Shh pathway to downstream targets. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and the context for the pathway to promote early retinal neurogenesis. The temporally distinct interactions between Lhx2 and the Shh pathway in retinal development illustrate how transcription factors and signaling pathways adapt to meet stage-dependent requirements of tissue formation.
Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from human induced pluripotent stem cells
Authors: Tamaoki Naritaka , Siebert Stefan , Maeda Takuya , Ha Ngoc-Han , Good Meghan L. , Huang Yin , Vodnala Suman Kumar , Haro-Mora Juan J. , Uchida Naoya , Tisdale John F. , Sweeney Colin L. , Choi Uimook , Brault Julie , Koontz Sherry , Malech Harry L. , Yamazaki Yasuhiro , Isonaka Risa , Goldstein David S. , Kimura Masaki , Takebe Takanori , Zou Jizhong , Stroncek David F. , Robey Pamela G. , Kruhlak Michael J. , Restifo Nicholas P. , Vizcardo Raul 
Published: April 2021

SUMMARYThe human definitive yolk sac is an important organ supporting the early developing embryo through nutrient supply and by facilitating the establishment of the embryonic circulatory system. However, the molecular and cellular biology of the human yolk sac remains largely obscure due to the lack of suitable in vitro models. Here, we show that human induced pluripotent stem cells (hiPSCs) co-cultured with various types of stromal cells as spheroids self-organize into yolk sac-like organoids without the addition of exogenous factors. Yolk sac-like organoids recapitulated a yolk sac specific cellular complement and structures as well as the functional ability to generate definitive hematopoietic progenitor cells (HPCs). Furthermore, sequential hemato-vascular ontogenesis could be observed during organoid formation. Notably, our organoid system can be performed in a scalable, autologous, and xeno-free condition, thereby providing an important model of human definitive yolk sac development and allows for efficient bulk generation of hiPSC-derived HPCs.
A closed-loop stimulation approach with real-time estimation of the instantaneous phase of neural oscillations by a Kalman filter
Authors: Onojima Takayuki , Kitajo Keiichi 
Published: April 2021

AbstractWe propose a novel method to estimate the instantaneous oscillatory phase to implement a real-time system for closed-loop sensory stimulation in electroencephalography (EEG) experiments. The method uses Kalman filter-based prediction to estimate current and future EEG signals. We tested the performance of our method in a real-time situation. We demonstrate that the performance of our method shows higher accuracy in predicting the EEG phase than the conventional autoregressive model-based method. A Kalman filter allows us to easily estimate the instantaneous phase of EEG oscillations based on the automatically estimated autoregressive model implemented in a real-time signal processing machine. The proposed method has a potential for versatile applications targeting the modulation of EEG phase dynamics and the plasticity of brain networks in relation to perceptual or cognitive functions.
Bacterial chaperone protein Hfq facilitates the annealing of sponge RNAs to small regulatory RNAs
Authors: Małecka Ewelina M. , Sobańska Daria , Olejniczak Mikołaj 
Published: April 2021

ABSTRACTBacterial small RNAs (sRNAs) in association with the chaperone protein Hfq regulate the expression of many target mRNAs. Since sRNAs’ action is crucial to engender a response to changing environmental conditions, their activity needs to be regulated. One such mechanism occurs at posttranscriptional level and involves sponge RNAs (or anti-sRNAs) which sequester sRNAs affecting their regulatory output. Both types of RNAs were identified on Hfq, but it is not known how Hfq interacts with RNA sponges and stimulates their base-pairing with sRNAs. Here, we used biochemical methods to demonstrate that anti-sRNAs resemble sRNAs by their structure and their modes of Hfq binding. Hfq facilitates sponge RNA annealing to sRNA, and each surface of the protein plays a particular role in the process. Moreover, we found that the efficiency of sponge RNA interactions with sRNAs can be improved, therefore, we propose that natural RNA sponges might not sequester sRNAs optimally.
Accuracy and Precision of Social Relationship Indices
Authors: Mielke Alexander , Samuni Liran 
Published: April 2021

AbstractCombining interaction rates of different social behaviours into social relationship indices to represent the structure of dyadic relationships on one underlying dimension is common practice in animal sociality studies. However, the properties of these relationship indices are not well explored – mainly because, for real-world social systems, the ‘true’ value of relationships is unobservable. Here, we use simulation studies to estimate the accuracy and precision of three relationship indices: the Dyadic Composite Sociality Index, the Composite Relationship Index, and the Dynamic Dyadic Sociality Index. We simulated one year of social interactions for multiple groups of 25 individuals and 4 interaction types with different properties, and tested the impact of different focal follow regimes, data densities and sampling conditions on the representation of social relationships. Accuracy and precision of social relationship indices were strongly driven by sample size, similar to simple interaction rates. Under the assumption that there was a clear, one-dimensional relationship underlying interactions, and that different interaction types constituting an index were highly correlated, indices indeed increased accuracy over single interaction rates for small sample sizes. Including uninformative constituting behaviours (i.e., those not highly correlated with the underlying relationship dimension) reduced the accuracy of all indices. The precision of each index (i.e., whether multiple simulated focal follow regimes achieve the same dyadic values for the same data) was generally poor and was driven by the precision of the least precise constituting behaviour, making them less precise than some single interaction rates. Our results showed that social relationship indices do not remove the need to have sufficient data for each individual constituting interaction type. Index quality was defined by the least accurate and precise constituting interaction type. Indices might only be useful if all constituting interaction rates are highly correlated and if there are clear indications that one dimension is sufficient to represent social relationships in a group.
Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals
Authors: Vanicek T , Reed MB , Unterholzner J , Klöbl M , Godbersen GM , Handschuh PA , Spurny B , Ritter V , Gryglewski G , Kraus C , Winkler D , Lanzenberger R , Seiger R 
Published: April 2021

AbstractBackgroundNeuroplastic processes are influenced by selective serotonergic reuptake inhibitors, while learning in conjunction with the administration of serotonergic agents alters white matter microstructure in humans. The goal of this double-blind, placebo-controlled imaging study was to investigate the influence of escitalopram on white matter plasticity during (re)learning.MethodsSeventy-one healthy individuals (age = 25.6±5.0, 43 females) underwent 3 diffusion magnetic resonance imaging sessions: at baseline, after 3-weeks of associative learning (emotional/non-emotional content) and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, subjects received daily escitalopram 10 mg or placebo orally. Statistical analysis was performed with statistical parametric mapping (SPM) and using sandwich estimator.ResultsA three-way and two-way rmANOVA was conducted to analyze the effects of escitalopram on AD, FA, MD and RD during the learning and relearning period. We found no significant three-way or two-way interactions for each DTI metrics (pFDR> 0.05), thus neither after 3 nor after 6 weeks we found significant changes in white matter microstructure.ConclusionWe examined neither an effect of escitalopram nor learning (or relearning) interventions on different DTI metrics. The duration and intensity of study interventions (i.e. administration of escitalopram and learning as the relearning task) might have been chosen insufficiently to induce detectable alterations. Previous studies examining the effects of SSRIs on white matter tracts in humans are underrepresented, but do mainly yield towards non-significant findings. The results implicate that escitalopram does not impact white matter microstructures in healthy subjects.
Plant demographic knowledge is biased towards short-term studies of temperate-region herbaceous perennials
Authors: Römer Gesa , Dahlgren Johan P. , Salguero-Gómez Roberto , Stott Iain M. , Jones Owen R. 
Published: April 2021

SummaryPlant population dynamics research has a long history, and data collection rates have increased through time. The inclusion of this information in databases enables researchers to investigate the drivers of demographic patterns globally and study life history evolution.Studies aiming to generalise demographic patterns rely on data being derived from a representative sample of populations. However, the data are likely to be biased, both in terms of the species and ecoregions investigated and in how the original studies were conducted.Matrix population models (MPMs) are a widely-used tool in plant demography, so an assessment of publications that have used MPMs is a convenient way to assess the distribution of plant demographic knowledge. We assessed bias in this knowledge using data from the COMPADRE Plant Matrix Database, which contains MPMs for almost 800 plant species.We show that tree species and tropical ecoregions are under-represented, while herbaceous perennials and temperate ecoregions are over-represented. In addition, there is a positive association between the number of studies per country and the wealth of the country. Furthermore, we found a strong tendency towards low spatiotemporal replication: More than 50% of the studies were conducted over fewer than 4 years, and only 17% of the studies have replication across >3 sites. This limited spatiotemporal coverage means that the data may not be representative of the environmental conditions experienced by the species.Synthesis: The biases and knowledge gaps we identify are a challenge for the progress of theory and limit the usefulness of current data for determining patterns that would be useful for conservation decisions, such as determining general responses to climate change. We urge researchers to close these knowledge gaps with novel data collection.
Kinetics and Mechanism of Fentanyl Dissociation from theµ-Opioid Receptor
Authors: Mahinthichaichan Paween , Vo Quynh N. , Ellis Christopher R. , Shen Jana 
Published: April 2021

AbstractDriven by illicit fentanyl, opioid related deaths have reached the highest level in 2020. Currently, an opioid over-dose is resuscitated by the use of naloxone, which competitively binds and antagonizes theµ-opioid receptor (mOR). Thus, knowledge of the residence times of opioids at mOR and the unbinding mechanisms is valuable for assessing the effectiveness of naloxone. In the present study we calculate the fentanyl-mOR dissociation time and elucidate the mechanism by applying an enhanced sampling molecular dynamics (MD) technique. Two sets of metadynamics simulations with different initial structures were performed while accounting for the protonation state of the conserved H2976.52, which has been suggested to modulate the ligand-mOR affinity and binding mode. Surprisingly, with the Nδ-protonated H2976.52, fentanyl can descend as much as 10 Å below the level of the conserved D1473.32before escaping the receptor, and has a calculated residence timeτof 38 s. In contrast, with the N - and doubly protonated H2976.52, the calculatedτare 2.6 s and 0.9 s, respectively. Analysis suggests that formation of the piperidine–Hid297 hydrogen bond strengthens the hydrophobic contacts with the transmembrane helix (TM) 6, allowing fentanyl to explore a deep pocket. Considering the experimentalτof ∼4 min for fentanyl and the role of TM6 in mOR activation, we suggest that the deep insertion mechanism may be biologically relevant. The work paves the way for large-scale computational predictions of opioid dissociation rates to inform the regulatory decision. The profound role of the histidine protonation state found here may shift the paradigm in computational studies of ligand-receptor kinetics.
The oldest peracarid crustacean reveals a Late Devonian freshwater colonisation by isopod relatives
Authors: Robin N. , Gueriau P. , Luque J. , Jarvis D. , Daley A.C. , Vonk R. 
Published: April 2021

AbstractPeracarida (e.g., woodlice & side-swimmers) are, together with their sister-group Eucarida (e.g. krill & decapods), the most speciose group of modern crustaceans, suggested to have appeared as early as the Ordovician. While eucarids incursion onto land consists of mainly freshwater and littoral grounds, some peracarids have evolved fully terrestrial ground-crawling ecologies, inhabiting even our gardens in temperate regions (e.g. pillbugs and sowbugs). Their fossil record extends back to the Carboniferous and consists mainly of marine occurrences. Here, we provide a complete re-analysis of a fossil arthropod –Oxyuropoda– reported in 1908 from the Late Devonian floodplains of Ireland, and left with unresolved systematic affinities despite a century of attempts at identification. Known from a single specimen preserved in two-dimensions, we analysed its anatomy using digital microscopy and multispectral macro-imaging to enhance contrast of morphological structures. The new anatomical characters and completeness ofOxyuropoda, together with a phylogenetic analysis with representatives of all major Eumalacostraca groups, indicate thatOxyuropodais a crown-peracarid, part of a clade including amphipods and isopods. As such,Oxyuropodais the oldest known Peracarida, and provides evidence that derived peracarids had an incursion into freshwater and terrestrial environments as early as the Famennian, more than 360 million years ago.
The F-box protein AFF1 regulates ARF protein accumulation to regulate auxin response
Authors: Jing Hongwei , Korasick David A. , Emenecker Ryan J. , Morffy Nicholas , Wilkinson Edward G. , Powers Samantha K. , Strader Lucia C. 
Published: April 2021

ABSTRACTAuxin critically regulates nearly every aspect of plant growth and development. Auxin-driven transcriptional responses are mediated through the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. Although ARF protein stability is regulated via the 26S proteasome, molecular mechanisms underlying ARF stability and turnover are unknown. Here, we report the identification and functional characterization of an F-box E3 ubiquitin ligase, which we have named AUXIN RESPONSE FACTOR F-BOX1 (AFF1). AFF1 directly interacts with ARF19 and regulates its accumulation. Mutants defective inAFF1display ARF19 protein hyperaccumulation, attenuated auxin responsiveness, and developmental defects. Together, our data suggest a new mechanism, namely control of ARF protein stability, in regulating auxin response.