bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution, associations and role in the biological carbon pump of Pyrosoma atlanticum (Tunicata, Thaliacea) off Cabo Verde, NE Atlantic
Authors: Stenvers Vanessa I. , Hauss Helena , Osborn Karen J. , Neitzel Philipp , Merten Véronique , Scheer Stella , Robison Bruce H. , Freitas Rui , Hoving Henk Jan T. 
Published: April 2021

AbstractGelatinous zooplankton are increasingly acknowledged to contribute significantly to the carbon cycle worldwide, yet many taxa within this diverse group remain poorly studied. Here, we investigate the pelagic tunicatePyrosoma atlanticumin the waters surrounding the Cabo Verde Archipelago. By using a combination of pelagic and benthic in situ observations, sampling, and molecular genetic analyses (barcoding, eDNA), we reveal that:P. atlanticumabundance is most likely driven by local island-induced productivity, that it substantially contributes to the organic carbon export flux and is part of a diverse range of biological interactions. Downward migrating pyrosomes actively transported an estimated 13% of their fecal pellets below the mixed layer, equaling a carbon flux of 1.96–64.55 mg C m−2 day−1. We show that analysis of eDNA can detect pyrosome material beyond their migration range, suggesting that pyrosomes have ecological impacts below the upper water column. MoribundP. atlanticumcolonies contributed an average of 15.09 ± 17.89 (s.d.) mg C m−2to the carbon flux reaching the island benthic slopes. Our pelagic in situ observations further show thatP. atlanticumformed an abundant substrate in the water column (reaching up to 0.28 m2substrate area per m2), with animals using pyrosomes for settlement, as a shelter and/or a food source. In total, twelve taxa from four phyla were observed to interact with pyrosomes in the midwater and on the benthos.
TRPM2 ion channels steer neutrophils towards a source of hydrogen peroxide
Authors: Morad Hassan , Luqman Suaib , Tan Chun-Hsiang , Swann Victoria , McNaughton Peter A. 
Published: April 2021

AbstractNeutrophils must navigate accurately towards pathogens in order to destroy invaders and thus defend our bodies against infection. Here we show that hydrogen peroxide, a potent neutrophil chemoattractant, guides chemotaxis by activating calcium-permeable TRPM2 ion channels and generating an intracellular leading-edge calcium “pulse”. The thermal sensitivity of TRPM2 activation means that chemotaxis towards hydrogen peroxide is strongly promoted by small temperature elevations, suggesting that an important function of fever may be to enhance neutrophil chemotaxis by facilitating calcium influx through TRPM2. Chemotaxis towards conventional chemoattractants such as LPS, CXCL2 and C5a does not depend on TRPM2 but is driven in a similar way by leading-edge calcium pulses. Other proposed initiators of neutrophil movement, such as PI3K, Rac and lyn, influence chemotaxis by modulating the amplitude of calcium pulses. We propose that intracellular leading-edge calcium pulses are universal drivers of the motile machinery involved in neutrophil chemotaxis.
Machine learning outperforms thermodynamics in measuring how well a many-body system learns a drive
Authors: Zhong Weishun , Gold Jacob M. , Marzen Sarah , England Jeremy L. , Yunger Halpern Nicole 
Published: April 2021

AbstractDiverse many-body systems, from soap bubbles to suspensions to polymers, learn and remember patterns in the drives that push them far from equilibrium. This learning may be leveraged for computation, memory, and engineering. Until now, many-body learning has been detected with thermodynamic properties, such as work absorption and strain. We progress beyond these macroscopic properties first defined for equilibrium contexts: We quantify statistical mechanical learning using representation learning, a machine-learning model in which information squeezes through a bottleneck. By calculating properties of the bottleneck, we measure four facets of many-body systems’ learning: classification ability, memory capacity, discrimination ability, and novelty detection. Numerical simulations of a classical spin glass illustrate our technique. This toolkit exposes self-organization that eludes detection by thermodynamic measures: Our toolkit more reliably and more precisely detects and quantifies learning by matter while providing a unifying framework for many-body learning.
Long-read-sequenced reference genomes of the seven major lineages of enterotoxigenic Escherichia coli (ETEC) circulating in modern time
Authors: von Mentzer Astrid , Blackwell Grace A. , Pickard Derek , Boinett Christine J. , Joffré Enrique , Page Andrew J. , Svennerholm Ann-Mari , Dougan Gordon , Sjöling Åsa 
Published: April 2021

AbstractEnterotoxigenic Escherichia coli (ETEC) is an enteric pathogen responsible for the majority of diarrheal cases worldwide. ETEC infections are estimated to cause 80,000 deaths annually, with the highest rates of burden, ca 75 million cases per year, amongst children under 5 years of age in resource-poor countries. It is also the leading cause of diarrhoea in travellers. Previous large-scale sequencing studies have found seven major ETEC lineages currently in circulation worldwide. We used PacBio long-read sequencing combined with Illumina sequencing to create high-quality complete reference genomes for each of the major lineages with manually curated chromosomes and plasmids. We confirm that the major ETEC lineages all harbour conserved plasmids that have been associated with their respective background genomes for decades, suggesting that the plasmids and chromosomes of ETEC are both crucial for ETEC virulence and success as pathogens. The in-depth analysis of gene content, synteny and correct annotations of plasmids will elucidate other plasmids with and without virulence factors in related bacterial species. These reference genomes allow for fast and accurate comparison between different ETEC strains, and these data will form the foundation of ETEC genomics research for years to come.
Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
Authors: Bertels Sarah , Jaggy Mona , Richter Benjamin , Keppler Stephan , Weber Kerstin , Genthner Elisa , Fischer Andrea C. , Thiel Michael , Wegener Martin , Greiner Alexandra M. , Autenrieth Tatjana J. , Bastmeyer Martin 
Published: April 2021

AbstractMechanotransduction via yes-associated protein (YAP) is a central mechanism for decision-making in mouse embryonic stem cells (mESCs). Nuclear localization of YAP is tightly connected to pluripotency and increases the cell division rate (CDR). How the geometry of the extracellular environment influences mechanotransduction, thereby YAP localization, and decision-making of single isolated mESCs is largely unknown. To investigate this relation, we produced well-defined 2D and 2.5D microenvironments and monitored CDR and subcellular YAP localization in single mESCs hence excluding cell–cell interactions. By systematically varying size and shape of the 2D and 2.5D substrates we observed that the geometry of the growth environment affects the CDR. Whereas CDR increases with increasing adhesive area in 2D, CDR is highest in small 2.5D micro-wells. Here, mESCs attach to all four walls and exhibit a cross-shaped cell and nuclear morphology. This observation indicates that changes in cell shape are linked to a high CDR. Inhibition of actomyosin activity abrogate these effects. Correspondingly, nuclear YAP localization decreases in inhibitor treated cells, suggesting a relation between cell shape, intracellular forces, and cell division rate. The simplicity of our system guarantees high standardization and reproducibility for monitoring stem cell reactions and allows addressing a variety of fundamental biological questions on a single cell level.
Multi-seasonal systematic camera-trapping reveals fluctuating densities and high turnover rates of Carpathian lynx on the western edge of its native range
Authors: Duľa Martin , Bojda Michal , Chabanne Delphine B. H. , Drengubiak Peter , Hrdý Ľuboslav , Krojerová-Prokešová Jarmila , Kubala Jakub , Labuda Jiří , Marčáková Leona , Oliveira Teresa , Smolko Peter , Váňa Martin , Kutal Miroslav 
Published: April 2021

AbstractCamera-trapping and capture-recapture models are the most widely used tools for estimating densities of wild felids that have unique coat patterns, such as Eurasian lynx. However, studies dealing with this species are predominantly on a short-term basis and our knowledge of temporal trends and population persistence is still scarce. By using systematic camera-trapping and spatial capture-recapture models, we estimated lynx densities and evaluated density fluctuations, apparent survival, transition rate and individual's turnover during five consecutive seasons at three different sites situated in the Czech–Slovak–Polish borderland at the periphery of the Western Carpathians. Our density estimates vary between 0.26 and 1.85 lynx/100 km2 suitable habitat and represent the lowest and the highest lynx densities reported from the Carpathians. We recorded 1.5–4.1-fold changes in asynchronous fluctuated densities among all study sites and seasons. Furthermore, we detected high individual’s turnover (on average 46.3 ± 8.06% in all independent lynx and 37.6 ± 4.22% in adults) as well as low persistence of adults (only 3 out of 29 individuals detected in all seasons). The overall apparent survival rate was 0.63 ± 0.055 and overall transition rate between sites was 0.03 ± 0.019. Transition rate of males was significantly higher than in females, suggesting male-biased dispersal and female philopatry. Fluctuating densities and high turnover rates, in combination with documented lynx mortality, indicate that the population in our region faces several human-induced mortalities, such as poaching or lynx-vehicle collisions. These factors might restrict population growth and limit the dispersion of lynx to other subsequent areas, thus undermining the favourable conservation status of the Carpathian population. Moreover, our study demonstrates that long-term camera-trapping surveys are needed for evaluation of population trends and for reliable estimates of demographic parameters of wild territorial felids, and can be further used for establishing successful management and conservation measures.
Orexinergic descending inhibitory pathway mediates linalool odor-induced analgesia in mice
Authors: Higa Yurina , Kashiwadani Hideki , Sugimura Mitsutaka , Kuwaki Tomoyuki 
Published: April 2021

AbstractLinalool odor exposure induces an analgesic effect in mice. This effect disappeared in the anosmic model mice, indicating that olfactory input evoked by linalool odor triggered this effect. Furthermore, hypothalamic orexinergic neurons play a pivotal role in this effect. However, the neuronal circuit mechanisms underlying this effect have not been fully addressed. In this study, we focused on the descending orexinergic projection to the spinal cord and examined whether this pathway contributes to the effect. We assessed the effect of intrathecal administration of orexin receptor antagonists on linalool odor-induced analgesia in the tail capsaicin test. We found that the selective orexin type 1 receptor antagonist, but not the selective orexin type 2 receptor antagonist, prevented the odor-induced analgesic effect. Furthermore, immunohistochemical analyses of c-Fos expression induced by the capsaicin test revealed that neuronal activity of spinal cord neurons was suppressed by linalool odor exposure, which was prevented by intrathecal administration of the orexin 1 receptor antagonist. These results indicate that linalool odor exposure drives the orexinergic descending pathway and suppresses nociceptive information flow at the spinal level.
Urinary neopterin of wild chimpanzees indicates that cell-mediated immune activity varies by age, sex, and female reproductive status
Authors: Negrey Jacob D. , Behringer Verena , Langergraber Kevin E. , Deschner Tobias 
Published: April 2021

AbstractThe study of free-living animal populations is necessary to understand life history trade-offs associated with immune investment. To investigate the role of life history strategies in shaping proinflammatory cell-mediated immune function, we analyzed age, sex, and reproductive status as predictors of urinary neopterin in 70 sexually mature chimpanzees (Pan troglodytes) at Ngogo, Kibale National Park, Uganda. In the absence of clinical signs of acute infectious disease, neopterin levels significantly increased with age in both male and female chimpanzees, as observed in humans and several other vertebrate species. Furthermore, males exhibited higher neopterin levels than females across adulthood. Finally, females with full sexual swellings, pregnant females, and post-reproductive females, the oldest individuals in our sample, exhibited higher neopterin levels than lactating females and cycling females without full swellings. Variation in females’ neopterin levels by reproductive status is consistent with post-ovulatory and pregnancy-related immune patterns documented in humans. Together, our results provide evidence of ample variation in chimpanzee immune activity corresponding to biodemographic and physiological variation. Future studies comparing immune activity across ecological conditions and social systems are essential for understanding the life histories of primates and other mammals.
Blue light blind-spot stimulation upregulates b-wave and pattern ERG activity in myopes
Authors: Amorim-de-Sousa Ana , Schilling Tim , Fernandes Paulo , Seshadri Yeshwanth , Bahmani Hamed , González-Méijome José Manuel 
Published: April 2021

AbstractUpregulation of retinal dopaminergic activity may be a target treatment for myopia progression. This study aimed to explore the viability of inducing changes in retinal electrical activity with short-wavelength light targeting melanopsin-expressing retinal ganglion cells (ipRGCs) passing through the optic nerve head. Fifteen healthy non-myopic or myopic young adults were recruited and underwent stimulation with blue light using a virtual reality headset device. Amplitudes and implicit times from photopic 3.0 b-wave and pattern electroretinogram (PERG) were measured at baseline and 10 and 20 min after stimulation. Relative changes were compared between non-myopes and myopes. The ERG b-wave amplitude was significantly larger 20 min after blind-spot stimulation compared to baseline (p < 0.001) and 10 min (p < 0.001) post-stimulation. PERG amplitude P50-N95 also showed a significant main effect for ‘Time after stimulation’ (p < 0.050). Implicit times showed no differences following blind-spot stimulation. PERG and b-wave changes after blind-spot stimulation were stronger in myopes than non-myopes. It is possible to induce significant changes in retinal electrical activity by stimulating ipRGCs axons at the optic nerve head with blue light. The results suggest that the changes in retinal electrical activity are located at the inner plexiform layer and are likely to involve the dopaminergic system.
OxCOVID19 Database, a multimodal data repository for better understanding the global impact of COVID-19
Authors: Mahdi Adam , Błaszczyk Piotr , Dłotko Paweł , Salvi Dario , Chan Tak-Shing , Harvey John , Gurnari Davide , Wu Yue , Farhat Ahmad , Hellmer Niklas , Zarebski Alexander , Hogan Bernie , Tarassenko Lionel 
Published: April 2021

AbstractOxford COVID-19 Database (OxCOVID19 Database) is a comprehensive source of information related to the COVID-19 pandemic. This relational database contains time-series data on epidemiology, government responses, mobility, weather and more across time and space for all countries at the national level, and for more than 50 countries at the regional level. It is curated from a variety of (wherever available) official sources. Its purpose is to facilitate the analysis of the spread of SARS-CoV-2 virus and to assess the effects of non-pharmaceutical interventions to reduce the impact of the pandemic. Our database is a freely available, daily updated tool that provides unified and granular information across geographical regions.

Design type
Data integration objective

Measurement(s)
Coronavirus infectious disease, viral epidemiology

Technology type(s)
Digital curation

Factor types(s)

Sample characteristic(s)
Homo sapiens
Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
Authors: Kaur Sukhneeraj P. , Verma Arti , Lee Hee. K. , Barnett Lillie M. , Somanath Payaningal R. , Cummings Brian S. 
Published: April 2021

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.
Surface modification of PMMA polymer and its composites with PC61BM fullerene derivative using an atmospheric pressure microwave argon plasma sheet
Authors: Sikora Andrzej , Czylkowski Dariusz , Hrycak Bartosz , Moczała-Dusanowska Magdalena , Łapiński Marcin , Dors Mirosław , Jasiński Mariusz 
Published: April 2021

AbstractThis paper presents the results of experimental investigations of the plasma surface modification of a poly(methyl methacrylate) (PMMA) polymer and PMMA composites with a [6,6]-phenyl-C61-butyric acid methyl ester fullerene derivative (PC61BM). An atmospheric pressure microwave (2.45 GHz) argon plasma sheet was used. The experimental parameters were: an argon (Ar) flow rate (up to 20 NL/min), microwave power (up to 530 W), number of plasma scans (up to 3) and, the kind of treated material. In order to assess the plasma effect, the possible changes in the wettability, roughness, chemical composition, and mechanical properties of the plasma-treated samples’ surfaces were evaluated by water contact angle goniometry (WCA), atomic force microscopy (AFM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The best result concerning the water contact angle reduction was from 83° to 29.7° for the PMMA material. The ageing studies of the PMMA plasma-modified surface showed long term (100 h) improved wettability. As a result of plasma treating, changes in the samples surface roughness parameters were observed, however their dependence on the number of plasma scans is irregular. The ATR-FTIR spectra of the PMMA plasma-treated surfaces showed only slight changes in comparison with the spectra of an untreated sample. The more significant differences were demonstrated by XPS measurements indicating the surface chemical composition changes after plasma treatment and revealing the oxygen to carbon ratio increase from 0.1 to 0.4.
Engineered adeno-associated virus 3 vector with reduced reactivity to serum antibodies
Authors: Ito Mika , Takino Naomi , Nomura Takamasa , Kan Akihiko , Muramatsu Shin-ichi 
Published: April 2021

AbstractThe natural serotypes of adeno-associated virus (AAV) or their variants, such as AAV8 and AAV5, are commonly used as vectors in the clinical programs for liver-targeted gene therapy. While AAV8 vectors are not highly efficient at targeting primary human hepatocytes, AAV3 vectors have recently demonstrated remarkable efficiency at targeting both human and non-human primate hepatocytes. However, the presence of high levels of neutralizing antibodies (NAbs) impedes transduction into hepatocytes, representing a major obstacle to the clinical application of AAV3 vectors. Herein, we engineered the viral capsid to reduce its reactivity with pre-existing NAbs, thereby enhancing the transduction efficiency. By introducing three substitutions (S472A, S587A, and N706A) on the surface loop of AAV3B capsid protein, we generated a triple mutant AAV3 (AAV.GT5) vector with less reactivity to anti-AAV capsid NAbs. While the transduction efficiency of AAV.GT5 into human hepatocellular cell lines was similar to those of parental AAV3B, it was 50-fold higher for hepatocytes derived from humanized mice compared to AAV8 vectors. Moreover, the AAV.GT5 vector yield was similar to those of the AAV2 and AAV3B vectors. Thus, high resistance to pre-existing NAbs makes AAV.GT5 a promising candidate for future liver-targeted gene therapy clinical trials.
Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment
Authors: Walo-Delgado Paulette Esperanza , Sainz de la Maza Susana , Villarrubia Noelia , Monreal Enric , Medina Silvia , Espiño Mercedes , Fernández-Velasco José Ignacio , Rodríguez-Martín Eulalia , Roldán Ernesto , Lourido Daniel , Muriel Alfonso , Masjuan-Vallejo Jaime , Costa-Frossard Lucienne , Villar Luisa María 
Published: April 2021

AbstractSerum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing–remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82–15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.