bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attentional enhancement of tracked stimuli in early visual cortex has limited capacity
Authors: Adamian Nika , Andersen Søren. K. 
Published: September 2022

AbstractKeeping track of the location of multiple simultaneously moving objects is one of the well documented functions of visual spatial attention. However, the mechanism of attentional selection that supports continuous tracking of several items is unclear. In particular, it has been proposed that target selection in early visual cortex occurs in parallel, with tracking errors arising due to attentional limitations at later processing stages. Here we examine whether, instead, total attentional capacity for enhancement of early visual processing of tracked targets is shared between all attended stimuli. If the magnitude of attentional facilitation of multiple tracked targets was a key limiting factor of tracking ability, then one should expect it to drop systematically with increasing set-size of tracked targets. Human observers (male and female) were instructed to track two, four, or six moving objects among a pool of identical distractors. Steady-state visual evoked potentials (SSVEPs) recorded during the tracking period revealed that the processing of tracked targets was consistently amplified compared to the processing of the distractors. The magnitude of this amplification decreased with increasing set size, and at lateral occipital electrodes it closely followed inverse proportionality to the number of tracked items, suggesting that limited attentional resources must be shared among the tracked stimuli. Accordingly, the magnitude of attentional facilitation predicted the behavioural outcome at the end of the trial. Together, these findings demonstrate that the limitations of multiple object tracking across set-sizes stem from the limitations of top-down selective attention already at the early stages of visual processing.Significance statementThe ability to selectively attend to relevant features or objects is the key to flexibility of perception and action in the continuously changing environment. This ability is demonstrated in the Multiple Object Tracking task where observers monitor multiple independently moving objects at different locations in the visual field. The role of early attentional enhancement in tracking was previously acknowledged in the literature, however, the limitations on tracking were thought to arise during later stages of processing. Here, we demonstrate that the strength of attentional facilitation depends on the number of tracked objects and predicts successful tracking performance. Thus, it is the limitations of attentional enhancement at the early stages of visual processing that determine behavioral performance limits.
RTK signalling promotes epithelial columnar cell shape and apical junction maintenance in human lung progenitor cells
Authors: Liu Shuyu , Sun Dawei , Butler Richard , Rawlins Emma L. 
Published: September 2022

ABSTRACTMultipotent epithelial progenitor cells can be expanded from human embryonic lungs as organoids. and maintained in a self-renewing state using a defined medium. The organoid cells are columnar, resembling the cell morphology of the developing lung tip epithelium in vivo. Cell shape dynamics and fate are tightly coordinated during development. We therefore used the organoid system to identify signalling pathways that maintain the columnar shape of human lung tip progenitors. We found that EGF, FGF7 and FGF10 have distinct functions in lung tip progenitors. FGF7 activates MAPK/ERK and PI3K/AKT signalling and is sufficient to promote columnar cell shape in primary tip progenitors. Inhibitor experiments show that MAPK/ERK and PI3K/AKT signalling are key downstream pathways, regulating cell proliferation, columnar cell shape and cell junctions. We identified integrin signalling as a key pathway downstream of MAPK/ERK in the tip progenitors; disrupting integrin alters polarity, cell adhesion and tight junction assembly. By contrast, stimulation with FGF10 or EGF alone is not sufficient to maintain organoid columnar cell shape. This study employs organoids to provide insight into the cellular mechanisms regulating human lung development.Summary statementRTK signalling activated MAPK/ERK and PI3K/AKT signalling regulates the shape and junctional structure of human lung epithelial progenitor cells during branching.
Multiscale assessment of oviposition habitat associations and implications for management in the spotted lanternfly (Lycorma delicatula), an emerging invasive pest
Authors: Ramirez Victoria A. , De Bona Sebastiano , Helmus Matthew R. , Behm Jocelyn E. 
Published: September 2022

AbstractControl of incipient invaders—established invasive species in the early stages of spreading— can be inhibited by incomplete knowledge of the species’ habitat use. By identifying consistent habitat associations for incipient invaders early, control efforts can be more effective. Yet, because habitat associations are the result of multiscale processes, approaches are needed for integrating data collected across scales to identify them.We employed a hierarchical, multiscale approach to identify oviposition habitat associations in the spotted lanternfly (Lycorma delicatula) an incipient invasive species of high concern in the United States. We targeted the oviposition habitat spatial scales most likely to be used by lanternflies and the spatial scales of explanatory environmental variables most easily used by managers to locate egg masses to control. We explored whether habitat associations exist for oviposition habitat use and how well habitat use is explained by the duration sites have been invaded. Finally, because habitat associations are likely driven by fitness, we determined if the use of any habitat types were associated with higher fitness as measured by the number of eggs per egg mass (i.e., fecundity).Spotted lanternflies exhibited oviposition habitat associations at the landscape, site, and tree scales. Overall, lanternflies oviposited more frequently at sites and on trees with low canopy cover in the surrounding landscape, on trees from the Acer genus, and in the crowns of larger trees beyond the reach of managers without special equipment. The duration a site had been invaded had opposing effects at the site and tree scales which indicates the need for scale-dependent management approaches.Despite the consistent habitat associations identified, no environmental variables explained variation in lanternfly fecundity, indicating more work is needed to identify environmental drivers of spotted lanternfly fitness.Synthesis and applications. Our results indicate a multiscale approach is needed for spotted lanternfly control with unique strategies for locating egg masses at sites and on trees that vary in invasion duration. Additionally, our results suggest that multiscale investigations of habitat associations would likely inform the control of other invasive species as well.
A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation
Authors: Bahar Mohammad W. , Nasta Veronica , Fox Helen , Sherry Lee , Grehan Keith , Porta Claudine , Macadam Andrew J. , Stonehouse Nicola J. , Rowlands David J. , Fry Elizabeth E. , Stuart David I. 
Published: September 2022

AbstractStrategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.
Ectodysplasin signaling via Xedar is required for mammary gland morphogenesis
Authors: Wark Abigail R. , Tomizawa Reiko , Aldea Daniel , Kokalari Blerina , Warder Bailey , Kamberov Yana G. 
Published: September 2022

ABSTRACTThe Ectodysplasin A2 receptor (XEDAR), is a member of the tumor necrosis factor receptor subfamily and is a mediator of the Ectodysplasin (EDA) signaling pathway. EDA signaling plays evolutionarily conserved roles in the development of the ectodermal appendage organ class that includes hair, eccrine sweat glands, and mammary glands. Loss of function mutations in Eda, which encodes the two major ligand isoforms, EDA-A1 and EDA-A2, result in X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by defects in two or more ectodermal appendage types. EDA-A1 and EDA-A2 signal through the receptors EDAR and XEDAR, respectively. While the contributions of the EDA-A1/EDAR signaling pathway to ectodermal appendage phenotypes have been extensively characterized, the significance of the EDA-A2/XEDAR branch of the pathway has remained obscure. Herein, we report the phenotypic consequences of disrupting the EDA-A2/XEDAR pathway on mammary gland differentiation and growth. Using a mouse Xedar knock-out model, we show that Xedar has a specific and temporally restricted role in promoting post-pubertal growth and branching of the mammary epithelium that can be influenced by genetic background. Our findings are the first to implicate Xedar in ectodermal appendage development and suggest that the EDA-A2/XEDAR signaling axis contributes to the etiology of EDA-dependent mammary phenotypes.
Extracellular Carbonic Anhydrase Supports Constitutive HCO3− Uptake in Fragilariopsis cylindrus Regardless of Temperature Changes
Authors: Li Meng , Young Jodi N. 
Published: September 2022

AbstractDiatoms, including Fragilariopsis cylindrus (Fcyl), are the major primary producers in productive polar oceans. Little is known about carbon concentrating mechanisms (CCMs) in polar diatoms and their sensitivity to ocean warming and acidification. Here we characterized the CCM response to temperature in Fcyl using Membrane Inlet Mass Spectrometry. Fcyl increases RuBisCO expression at lower temperatures to compensate slower catalytic rates but maintains a reliance on HCO3− uptake across different temperatures (−2 °C to 9 °C) despite higher CO2 solubility at colder temperatures. However, when external carbonic anhydrase (eCA) is inhibited, inorganic carbon usage switches from HCO3− uptake to a dependency on CO2 diffusion. Incorporating these measurements with modeling, we propose that relying on eCA supported HCO3− uptake is an adaptive strategy to the highly dynamic polar ocean environment which experience large fluctuations in [CO2] but where HCO3− is constantly available.
PlrA (MSMEG_5223) is an essential polar growth regulator in Mycobacterium smegmatis
Authors: Quintanilla Samantha Y. , Arejan Neda Habibi , Patel Parthvi B. , Boutte Cara C. 
Published: September 2022

AbstractMycobacteria expand their cell walls at the cell poles in a manner that is not well described at the molecular level. In this study, we identify a new factor, PlrA, involved in restricting peptidoglycan metabolism to the cell poles in Mycobacterium smegmatis. We show that PlrA localizes to the pole tips, and we identify its essential domain. We show that depletion of plrA pheno-copies depletion of polar growth factor Wag31, and that PlrA is involved in regulating polar peptidoglycan metabolism and the structure of the Wag31 polar foci.
Grasshopper genome reveals long-term conservation of the X chromosome and temporal variation in X chromosome evolution
Authors: Li Xinghua , Mank Judith E. , Ban Liping 
Published: September 2022

AbstractWe present the first chromosome-level genome assembly of the grasshopper, Locusta migratoria, one of the largest insect genomes. We use coverage differences between females (XX) and males (X0) to identify the X chromosome gene content, and find that the X chromosome shows both complete dosage compensation in somatic tissues and an underrepresentation of testes-expressed genes. Remarkably, X-linked gene content from L. migratoria is highly conserved across four insect orders, namely Orthoptera, Hemiptera, Coleoptera and Diptera, and the 800 Mb grasshopper X chromosome is homologous to the fly ancestral X chromosome despite 400 million years of divergence, suggesting either repeated origin of sex chromosomes with highly similar gene content, or long-term conservation of the X chromosome. We use this broad conservation of the X chromosome to test for temporal dynamics to Fast-X evolution, and find evidence of a recent burst evolution for new X-linked genes in contrast to slow evolution of X-conserved genes. Additionally, our results reveal the X chromosome represents a hotspot for adaptive protein evolution related migration and the locust swarming phenotype. Overall, our results reveal a remarkable case of conservation and adaptation on the X chromosome.
Fluorescence Lifetime: Beating the IRF and interpulse window
Authors: Fazel Mohamadreza , Vallmitjana Alexander , Scipioni Lorenzo , Gratton Enrico , Digman Michelle A. , Pressé Steve 
Published: September 2022

AbstractFluorescence lifetime imaging (FLIM) has been essential in capturing spatial distributions of chemical species across cellular environments employing pulsed illumination confocal setups. However, quantitative interpretation of lifetime data continues to face critical challenges. For instance, fluorescent species with knownin vitroexcited state lifetimes may split into multiple species with unique lifetimes when introduced into complex living environments. What is more, mixtures of species, that may be both endogenous and introduced into the sample, may exhibit; 1) very similar lifetimes; as well as 2) wide ranges of lifetimes including lifetimes shorter than the instrumental response function (IRF) or whose duration may be long enough to be comparable to the interpulse window. By contrast, existing methods of analysis are optimized for well-separated and intermediate lifetimes. Here we broaden the applicability of fluorescence lifetime analysis by simultaneously treating unknown mixtures of arbitrary lifetimes– outside the intermediate, goldilocks, zone–for data drawn from a single confocal spot leveraging the tools of Bayesian nonparametrics (BNP). We benchmark our algorithm, termed BNP-lifetime analysis of BNP-LA, using a range of synthetic and experimental data. Moreover, we show that the BNP-LA method can distinguish and deduce lifetimes using photon counts as small as 500.
Migrating mesoderm cells self-organize into a dynamic meshwork structure during chick gastrulation
Authors: Nakaya Yukiko , Tarama Mitsusuke , Tasaki Sohei , Isomura Ayako , Shibata Tatsuo 
Published: September 2022

AbstractMigration of cell populations is a fundamental process in morphogenesis and disease. The mechanisms of collective cell migration of epithelial cell populations have been well studied. It remains unclear, however, how the highly motile mesenchymal cells, which migrate extensively throughout the embryo, are connected with each other and coordinated as a collective. During gastrulation in chick embryos, the mesoderm cells, that are formed by an epithelial-to-mesenchymal transition (EMT), migrate in the 3D space between ectoderm and endoderm of the embryo. Using live imaging and quantitative analysis, such as topological data analysis (TDA), we found that the mesoderm cells undergo a novel form of collective migration, in which they form a meshwork structure while moving away from the primitive streak. This meshwork is supported by N-cadherin-mediated cell-cell adhesion, which undergoes rapid reorganization. Overexpressing a mutant form of N-cadherin decreases the speed of tissue progression and the directionality of the collective cell movement, whereas the speed of individual cells remains unchanged. To investigate how this meshwork arises and how it contributes to the cell movement, we utilized an agent-based theoretical model, showing that cell elongation, cell-cell adhesion, and cell density are the key parameters for the meshwork formation. These data provide novel insights into how a supracellular structure of migrating mesenchymal cells forms and how it facilitates efficient migration during early mesoderm formation.
Functional characterization of the Co2+transporter AitP inSinorhizobium meliloti: a new player in Fe2+homeostasis
Authors: Mihelj Paula , Abreu Isidro , Moreyra Tomás , González-Guerrero Manuel , Raimunda Daniel 
Published: September 2022

AbstractCo2+induces the increase of the labile-Fe pool (LIP) by Fe-S cluster damage, heme synthesis inhibition and “free” iron import, which affects cell viability. The N2-fixing bacteria,Sinorhizobium meliloti, is a suitable model to determine the roles of Co2+-transporting Cation diffusion facilitator exporters (Co-eCDF) in Fe2+homeostasis because it has a putative member of this sub-family, AitP, and two specific Fe2+-export systems. An insertional mutant of AitP showed Co2+sensitivity and accumulation, Fe accumulation and hydrogen peroxide sensitivity, but not Fe2+sensitivity, despite AitP being abona fidelow affinity Fe2+exporter as demonstrated by the kinetic analyses of Fe2+uptake into everted membrane vesicles. Suggesting concomitant Fe2+-dependent induced stress, Co2+sensitivity was increased in strains carrying mutations in AitP and Fe2+exporters which did not correlate with the Co2+accumulation. Growth in the presence of sub-lethal Fe2+and Co2+concentrations suggested that free Fe-import might contribute to Co2+toxicity. Supporting this, Co2+induced transcription of Fe-import system and genes associated with Fe homeostasis. Analyses of total protoporphyrin content indicates Fe-S cluster attack as the major source for LIP. AitP-mediated Fe2+-export is likely counterbalanced via a non-futile Fe2+-import pathway. Two lines of evidence support this: i) an increased hemin uptake in presence of Co2+was observed in WTvs. AitP mutant, and ii) hemin reversed the Co2+sensitivity in the AitP mutant. Thus, the simultaneous detoxification mediated by AitP aids cells to orchestrate an Fe-S cluster salvage response, avoiding the increase in the LIP caused by the disassembly of Fe-S clusters or free iron uptake.ImportanceCross-talk between iron and cobalt has been long recognized in biological systems. This is due to the capacity of cobalt to interfere with proper iron utilization. Cells can detoxify cobalt by exporting mechanisms involving membrane proteins known as exporters. Highlighting the cross-talk, the capacity of several cobalt exporters to also export iron is emerging. Although biologically less important than Fe2+, Co2+induces toxicity by promoting intracellular Fe release, which ultimately causes additional toxic effects. In this work, we describe how the N2-fixating rhizobial cells solve this perturbation by clearing Fe through a Co2+-exporter, in order to reestablish intracellular Fe-levels by importing non-free Fe, heme. This piggyback-ride type of transport may aid bacterial cells to survive in free-living conditions where high anthropogenic Co2+content may be encountered.
Effectiveness of BNT162b2 and CoronaVac against pediatric COVID-19-associated hospitalization and moderate-to-severe disease
Authors: Rosa Duque Jaime S. , Leung Daniel , Yip Ka Man , Lee Derek H.L. , So Hung-kwan , Wong Wilfred H.S. , Lau Yu Lung 
Published: September 2022

ABSTRACTBackgroundVaccine effectiveness (VE) of BNT162b2 and CoronaVac against COVID-19-associated hospitalization and moderate-to-severe disease due to SARS-CoV-2 Omicron BA.2 for pediatric populations that had low exposure to prior SARS-CoV-2 variants needs to be further clarified. This can be studied from the 1.36 million vaccine doses had been administered to 766,601 of 953,400 children and adolescents in Hong Kong (HK) since March 2021 to April 2022.MethodsUsing an ecological design leveraging the HK vaccination coverage statistics and public hospital records, this study investigated the VE for children aged 3-11 years and adolescents aged 12-18 years at the population level during the Omicron BA.2 wave from January to April 2022.FindingsVE against COVID-19-associated hospitalization for children was 65.3% for 1 dose of BNT162b2 and 13.0% and 86.1% for 1 and 2 doses of CoronaVac, respectively. For adolescents, VE against COVID-19-associated hospitalization was 60.2% and 82.4% after 1 and 2 doses of BNT162b2 and 30.8% and 90.7% after 1 and 2 doses of CoronaVac, respectively. Protection against moderate-to-severe disease for aged 3-18 was high, with VE of 93.1% and 95.8% after 2 doses of BNT162b2 and CoronaVac, respectively. No COVID-19-associated hospitalization or moderate-to-severe disease occurred for 68,565 children and adolescents who received their third dose. Estimated hospitalizations of children and adolescents averted by vaccination were 68 and 999, respectively, and were 45 and 147 for moderate-to-severe cases.ConclusionsBNT162b2 or CoronaVac provide substantial protection from COVID-19-associated hospitalization and moderate-to-severe disease due to a SARS-CoV-2 variant of concern.FundingThe Providence Foundation.