bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using 3D geometric morphometrics to aid taxonomic and ecological understanding of a recent speciation event within a small Australian marsupial (genusAntechinus)
Authors: Viacava Pietro , Baker Andrew M. , Blomberg Simone P. , Phillips Matthew J. , Weisbecker Vera 
Published: April 2021

AbstractTaxonomic distinction of species forms the foundation of biodiversity assessments and conservation priorities. However, traditional morphological and/or genetics-based taxonomic assessments frequently miss the opportunity of elaborating on the ecological and functional context of species diversification. Here, we used 3D geometric morphometrics of the cranium to improve taxonomic differentiation and add eco-morphological characterisation of a young cryptic divergence within the marsupial carnivorous genusAntechinus. Specifically, we used 168 museum specimens to characterise the recently proposed cladesA. stuartii“south”,A. stuartii“north” andA. subtropicus. Beyond slight differences attributable to overall size (and therefore not necessarily diagnostic), we also found clear allometry-independent shape variation. This allowed us to define new, easily measured diagnostic traits in the palate, which differentiate the three clades. Contrary to previous suggestions, we found no support for a latitudinal gradient as causing the differentiation between the clades. However, skull shape co-varied with temperature and precipitation seasonality, suggesting that the clades may be adapted to environmental variables that are likely to be impacted by climate change. Our study demonstrates the use of 3D geometric morphometrics to improve taxonomic diagnosis of cryptic mammalian species, while providing perspectives on the adaptive origins and potential future threats of mammalian diversity.
Generation of specialized blood vessels through transdifferentiation of lymphatic endothelial cells
Authors: Das Rudra N. , Bassi Ivan , Han Yanchao , Lambiase Giuseppina , Tevet Yaara , Moshe Noga , Safriel Stav , Nicenboim Julian , Brückner Matthias , Hirsch Dana , Eilam-Altstadter Raya , Herzog Wiebke , Poss Kenneth D. , Yaniv Karina 
Published: April 2021

AbstractThe lineage and developmental trajectory of a cell are key determinants of cellular identity. Yet, the functional relevance of deriving a specific cell type from ontologically distinct progenitors, remains an open question. In the case of the vascular system, blood and lymphatic vessels are composed of endothelial cells (ECs) that differentiate and diversify to cater the different physiological demands of each organ. While lymphatic vessels have been shown to originate from multiple cell sources, lymphatic ECs (LECs) themselves seem to have a unipotent cell fate. In this work we uncover a novel mechanism of blood vessel formation through transdifferentiation of LECs. Using advanced long-term reiterative imaging and lineage-tracing of ECs in zebrafish, from embryonic development through adulthood, we reveal a hitherto unknown process of LEC-to-BEC transdifferentiation, underlying vascularization of the anal fin (AF). Moreover, we demonstrate distinct functional implications for deriving AF vessels from either LECs or BECs, uncovering for the first time a clear link between cell ontogeny and functionality. Molecularly, we identify Sox17 as a negative regulator of lymphatic fate specification, whose specific expression in AF LECs suppresses its lymphatic cell fate. Finally, we show that akin to the developmental process, during adult AF regeneration the vasculature is re-derived from lymphatics, demonstrating that LECs in the mature fish retain both potency and plasticity for generating specialized blood vessels. Overall, our work highlights a novel mechanism of blood vessel formation through LEC trans-differentiation, and provides the firstin vivoevidence for a link between cell ontogeny and functionality in ECs.
Distinct functions of cardiac β-adrenergic receptors in the T-tubulevs.outer surface membrane
Authors: Barthé Marion , Lefebvre Flora , Langlois Emilie , Lefebvre Florence , Lechêne Patrick , Iturrioz Xavier , Llorens-Cortes Catherine , Ha-Duong Tâp , Moine Laurence , Tsapis Nicolas , Fischmeister Rodolphe 
Published: April 2021

Abstractβ-adrenoceptors (β-ARs) regulate cardiac function during sympathetic nerve stimulation. β-ARs are present in both cardiac T-tubule (TTM) and outer surface membrane (OSM), but how their location impacts on their function is unknown. Here, we developed a technology based on size exclusion to explore the function of β-ARs located in the OSM. We synthetized a PEG-Iso molecule by covalent linking isoprenaline (Iso) to a 5000 Da PolyEthylene-Glycol (PEG) chain to increase the size of the β-AR agonist and prevent it from accessing the TT network. The affinity of PEG-Iso and Iso on β1- and β2-ARs was measured using radioligand binding. Molecular dynamics simulation was used to assess PEG-Iso conformation and visualise the accessibility of the Iso moiety to water. Using confocal microscopy, we show that PEGylation constrains molecules outside the T-tubule network due to the presence of the extracellular matrix. β-AR activation in OSM with PEG-Iso produced a lower stimulation of [cAMP]ithan Iso but a larger stimulation of cytosolic PKA at equivalent levels of [cAMP]Iand similar effects on excitation-contraction coupling parameters. However, PEG-Iso produced a much lower stimulation of nuclear PKA than Iso. Thus, OSM β-ARs control mainly cytosolic cAMP/PKA pathway and contractility, while TTM β-ARs control mainly nuclear PKA and nuclear protein phosphorylation. Size exclusion strategy using ligand PEGylation provides a unique approach to evaluate the respective contribution of T-tubulevs.outer surface membrane proteins in cardiac cells.Significance Statementβ-adrenoceptors (β-ARs) regulate cardiac function during sympathetic nerve stimulation. They are present in both cardiac T-tubule and outer surface membranes, but how their location impacts on their function is unknown. By linking the β-AR agonist isoprenaline (Iso) to a PolyEthylene-Glycol (PEG) chain, we increased the size of the agonist to prevent it from entering the T-tubules. Thus, PEG-Iso is only able to activate β-ARs in the outer surface membrane. With this size exclusion strategy, we show that β-ARs located in the outer surface membrane control mainly cytosolic cAMP/PKA pathway and contractility, while those located in the T-tubule membrane control mainly nuclear PKA and nuclear protein phosphorylation.
Nanoscale ligand density modulates gap junction intercellular communication of cell condensates during chondrogenesis
Authors: Casanellas Ignasi , Lagunas Anna , Vida Yolanda , Pérez-Inestrosa Ezequiel , Rodríguez-Pereira Cristina , Magalhaes Joana , Andrades José A. , Becerra José , Samitier Josep 
Published: April 2021

AbstractTo unveil the influence of cell-matrix adhesions in the establishment of gap junction intercellular communication (GJIC) during cell condensation in chondrogenesis.Materials & MethodsPreviously developed nanopatterns of the cell adhesive ligand arginine-glycine-aspartic acid (RGD) were used as cell culture substrates to control cell adhesion at the nanoscale. We conductedin vitrochondrogenesis of mesenchymal stem cells on the nanopatterns. We evaluated cohesion and GJIC in cell condensates.ResultsMechanical stability and GJIC are enhanced by a nanopattern configuration in which 90% of the surface area presents adhesion sites separated less than 70 nm, thus providing an onset for cell signaling.ConclusionCell-matrix adhesions regulate GJIC of mesenchymal cell condensates duringin vitrochondrogenesis from a threshold configuration at the nanoscale.
Recovery from form-deprivation myopia in chicks is dependent upon the fullness and correlated colour temperature of the light spectrum
Authors: Muralidharan Arumugam R. , Yu Shermaine Low Wan , Chong Lee Yong , Barathi Veluchamy A. , Saw Seang-Mei , Milea Dan , Najjar Raymond P. 
Published: April 2021

AbstractBackgroundTo evaluate the impact of full-spectrum light-emitting diodes (LEDs) mimicking sunlight on ocular axial elongation and refractive error development in a chicken model of myopia.MethodsA total of 39 chicks (Lohmann brown), 1 day-old, were randomly distributed into 3 groups. Animals were housed for 28 days in a temperature-controlled enclosure, under a 12/12h light/dark cycle of isoluminant (∼285 Lux) fluorescent [n = 18, (4000K, FL-4000)] or Sunlike-LED [n=12, (4000K, SL-4000); n = 9, (6500K, SL-6500)] white lights. Myopia was induced monocularly in all chicks by random occlusion of one eye with a frosted diffuser, from day 1 post-hatching (D1) until D14. On D14, diffusers were removed, and recovery from myopia was monitored under the same experimental light condition. Axial length (AL), refractive status, choroidal thickness and anterior chamber depth were recorded on days 1, 7, 14, 22 and 28.Ex vivoscleral collagen fibre thicknesses were measured from scanning electron microscopy images. Differences in outcome measures between eyes and groups were compared using 2-way repeated-measures ANOVA.ResultsThere was no significant difference between groups in the AL and refraction of form-deprived (FD) eyes during form-deprivation (D1 to D14). FD eyes of animals raised under SL-4000 and SL-6500 recovered more rapidly from excessive axial elongation than those of animals raised under FL-4000, by D22 and D28. Correspondingly, the refractive status of FD eyes exposed to SL-4000 and SL-6500 was close to that of control eyes by D28. The choroid became thicker during recovery in FD eyes compared to control eyes, in all groups. Choroidal thickness was significantly greater in FD eyes of chickens raised under SL-6500 than in animals raised under FL-4000 (P< 0.01). The diameter of scleral collagen fibrils was significantly greater in recovering FD eyes of chickens raised under SL-6500, than in those raised under FL-4000 (P= 0.04) and SL-4000 (P= 0.002).ConclusionsCompared to fluorescent light, moderate intensities of full-spectrum Sunlike-LEDs can accelerate recovery from form-deprivation myopia in chickens, potentially through choroid-mediated pathways increasing the diameter of scleral collagen fibrils. This study highlights an important implication of the spectral content of white light on ocular growth and emmetropization.
Experience-dependent plasticity modulates ongoing activity in the antennal lobe and enhances odor representations
Authors: Franco Luis M. , Yaksi Emre 
Published: April 2021

ABSTRACTOngoing neural activity has been observed across several brain regions and thought to reflect the internal state of the brain. Yet, it is not fully understood how ongoing brain activity interacts with sensory experience and shape sensory representations. Here, we show that projection neurons of the fruit fly antennal lobe exhibit spatiotemporally organized ongoing activity in the absence of odor stimulation. Upon repeated exposure to odors, we observe a gradual and long-lasting decrease in the amplitude and frequency of spontaneous calcium events, as well as a reorganization of correlations between olfactory glomeruli during ongoing activity. Accompanying these plastic changes, we find that repeated odor experience reduces trial-to-trial variability and enhances the specificity of odor representations. Our results reveal a previously undescribed experience-dependent plasticity of ongoing and sensory driven activity at peripheral levels of the fruit fly olfactory system.
Effect of anthropogenic vibratory noise on plant development and herbivory
Authors: Velilla Estefania , Bellato Laura , Collinson Eleanor , Halfwerk Wouter 
Published: April 2021

AbstractA growth in anthropogenic activities and infrastructure has led to increasing subterranean vibratory noise levels. Inland wind energy turbines, which are mostly located in agricultural fields, are a fast growing source of vibrational noise. Plants, which are rooted in the soil are constantly exposed to windmill-induced vibrations propagating through the ground. We have little understanding on how anthropogenic seismic vibrations affect plant development and how that in turn can affect plant-insect interactions. In this study we investigated the effect of windmill-like underground vibrational noise on plant development and on a plant-herbivore interaction. We experimentally exposedPisum sativumplants from seed stage to seed production stage to high and low vibrational noise levels and monitored them daily. We recorded germination, flowering and fruiting time, as well as daily shoot-length growth. Moreover, we tested the direct and indirect effects of vibrational noise on herbivory intensity by the generalist caterpillarSpodoptera exigua. We found that plants exposed to high vibrational noise grew significantly faster and taller than plants exposed to low vibrational noise. Additionally, plants treated with high noise germinated, flowered and produced fruits quicker than those treated with low noise. However, the differences in germination time, flowering time and fruiting time between the treatments were not statistically significant. Furthermore, we did not find an effect of vibrational noise on herbivory intensity. Vibrational noise could have consequences for both natural plant communities and agricultural crops by altering interspecific competition and by shifting growth-defence activation trade-offs.
Ability of known colorectal cancer susceptibility SNPs to predict colorectal cancer risk: A cohort study within the UK Biobank
Authors: Gafni Aviv , Dite Gillian S. , Tuff Erika Spaeth , Allman Richard , Hopper John L. 
Published: April 2021

AbstractColorectal cancer risk stratification is crucial to improve screening and risk-reducing recommendations, and consequently do better than a one-size-fits-all screening regimen. Current screening guidelines in the UK, USA and Australia focus solely on family history and age for risk prediction, even though the vast majority of the population do not have any family history. We investigated adding a polygenic risk score based on 45 single-nucleotide polymorphisms to a family history model (combined model) to quantify how it improves the stratification and discriminatory performance of 10-year risk and full lifetime risk using a prospective population-based cohort within the UK Biobank. For both 10-year and full lifetime risk, the combined model had a wider risk distribution compared with family history alone, resulting in improved risk stratification of nearly 2-fold between the top and bottom risk quintiles of the full lifetime risk model. Importantly, the combined model can identify people (n=72,019) who do not have family history of colorectal cancer but have a predicted risk that is equivalent to having at least one affected first-degree relative (n=44,950). We also confirmed previous findings by showing that the combined full lifetime risk model significantly improves discriminatory accuracy compared with a simple family history model 0.673 (95% CI 0.664–0.682 versus 0.666 (95% CI 0.657–0.675), p=0.0065. Therefore, a combined polygenic risk score and first-degree family history model could be used to improve risk stratified population screening programs.
Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture in humans
Authors: Domínguez Conde C , Xu C , Jarvis LB , Gomes T , Howlett SK , Rainbow DB , Suchanek O , King HW , Mamanova L , Polanski K , Huang N , Fasouli ES , Mahbubani KT , Prete M , Tuck L , Richoz N , Tuong ZK , Campos L , Mousa HS , Needham EJ , Pritchard S , Li T , Elmentaite R , Park J , Menon DK , Bayraktar OA , James LK , Meyer KB , Clatworthy MR , Saeb-Parsy K , Jones JL , Teichmann SA 
Published: April 2021

AbstractDespite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing.One Sentence SummaryWe provide an immune cell atlas, including antigen receptor repertoire profiling, across lymphoid and non-lymphoid human tissues.
A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells
Authors: Carmen Joshua M. , Shrivastava Shikha , Lu Zhongyan , Anderson Alexander , Morrison Elaine B. , Sankhala Rajeshwer S. , Chen Wei-Hung , Chang William C. , Bolton Jessica S. , Matyas Gary R. , Michael Nelson L. , Joyce M. Gordon , Modjarrad Kayvon , Currier Jeffrey R. , Bergmann-Leitner Elke , Malloy Allison M.W. , Rao Mangala 
Published: April 2021

AbstractPotent cellular responses to viral infections are pivotal for long -lived protection. Evidence is growing that these responses are critical in SARS -CoV-2 immunity. Assessment of a SARS -CoV-2 spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel® (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment of highly activated classical and non -classical antigen presenting cells (APCs) to the vaccine-draining lymph nodes of mice. The multifaceted APC response of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike -specific T cells with a bias towards TH1 responses and more robust SARS-CoV-2 spike-specific recall response. In addition, SpFN+ALFQ induced Kbspike(539-546)-specific memory CD8+T cells with effective cytolytic function and distribution to the lungs. This epitope is also present in SARS-CoV, thus suggesting that generation of cross-reactive T cells may provide protection against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant, generates effective SARS-CoV-2 specific innate and adaptive immune T cell responses that are key components to inducing long-lived immunity.One Sentence SummarySpFN vaccine generates multifactorial cellular immune responses.
In search for the most optimal EEG method: A practical evaluation of a water-based electrode EEG system
Authors: Topor Marta , Opitz Bertram , Dean Philip J. A. 
Published: April 2021

AbstractThe study assessed a mobile electroencephalography (EEG) system with water-based electrodes for its applicability in cognitive and behavioural neuroscience. It was compared to a standard gel-based wired system. EEG was recorded on two occasions (first with gel-based, then water-based system) as participants completed the flanker task. Technical and practical considerations for the application of the water-based system are reported based on participant and experimenter experiences. Empirical comparisons focused on EEG data noise levels, frequency power across four bands (theta, alpha, low beta and high beta) and event-related components (P300 and ERN). The water-based system registered more noise compared to the gel-based system which resulted in increased loss of data during artefact rejection. Signal to noise ratio was significantly lower for the water-based system in the parietal channels which impacted the observed parietal beta power. It also led to a shift in topography of the maximal P300 activity from parietal to frontal regions. It is also evident, that the water-based system may be prone to slow drift noise which may affect the reliability and consistency of low frequency band analyses. Practical considerations for the use of water-based electrode EEG systems are provided.
Evaluation of the virucidal efficacy of Klaran UVC LEDs against surface dried norovirus
Authors: Mariita Richard M. , Wilson Miller Amy C. , Randive Rajul V. 
Published: April 2021

AbstractHuman norovirus (HuNoV) is a highly contagious pathogenic virus that is transmitted through contaminated food, water, high-touch surfaces and aerosols. Globally, there are an estimated 685 million infections annually due to norovirus, among them 200 million children under the age of 5, causing approximately 50,000 child deaths per year and costing an estimated $60 billion annually in healthcare. In the USA, HuNoV is responsible for 19-21 million illnesses, with an average of 570-800 deaths per year. HuNoV is especially pernicious because it requires less than 100 viral particles to cause an infection, and there are few effective disinfectants. It is believed that Ultraviolet Subtype C (UVC) irradiation might prove to be an effective disinfectant. This study seeks to determine the inactivation profile of UVC against norovirus using a Klaran UVC Light-emitting diode (LED) array product number KL265-50V-SM-WD, emitting radiation at 269 nm peak wavelength and a measured fluence of 1.25 mW/cm2at a 7 cm source-surface distance. Since the HuNoV cannot currently be propagated in cell cultures, the study utilized feline calicivirus (FCV), a recommended surrogate as challenge organism. The test followed Modified ASTM E2197. Assessment of virus inactivation was performed using plaque assay method, with Crystal Violet as a staining agent to enhance plaque visualization. Within 18 seconds of exposure time at a UVC irradiance of 1.25mW/cm2and a dose of 22.5 mJ/cm2, the study obtained 99.9 % virus reduction (3 log reduction value). These results demonstrate that Klaran UVC-LED array (KL265-50V-SM-WD) can provide effective inactivation of HuNoV.
Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions
Authors: Glorieux Laura , Sapala Aleksandra , Willnow David , Moulis Manon , Edri Shlomit , Darrigrand Jean-Francois , Schonblum Anat , Sakhneny Lina , Schaumann Laura , Gómez Harold F. , Lang Christine , Conrad Lisa , Guillemot Fabien , Levenberg Shulamit , Landsman Limor , Iber Dagmar , Pierreux Christophe , Spagnoli Francesca M. 
Published: April 2021

AbstractGenerating comprehensive image maps, while preserving spatial 3D context, is essential to quantitatively assess and locate specific cellular features and cell-cell interactions during organ development. Despite the recent advances in 3D imaging approaches, our current knowledge of the spatial organization of distinct cell types in the embryonic pancreatic tissue is still largely based on 2D histological sections. Here, we present a light-sheet fluorescence microscopy approach to image the pancreas in 3D and map tissue interactions at key development time points in the mouse embryo. We used transgenic mouse models and antibodies to visualize the three main cellular components within the developing pancreas, including epithelial, mesenchymal and endothelial cell populations. We demonstrated the utility of the approach by providing volumetric data, 3D distribution of distinct progenitor populations and quantification of relative cellular abundance within the tissue. Lastly, our image data were combined in an open source online repository (referred to as Pancreas Embryonic Cell Atlas). This image dataset will serve the scientific community by enabling further investigation on pancreas organogenesis but also for devising strategies for thein vitrogeneration of transplantable pancreatic tissue for regenerative therapies.