bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection and transmission of ancestral SARS-CoV-2 and its alpha variant in pregnant white-tailed deer
Authors: Cool Konner , Gaudreault Natasha N. , Morozov Igor , Trujillo Jessie D. , Meekins David A. , McDowell Chester , Carossino Mariano , Bold Dashzeveg , Kwon Taeyong , Balaraman Velmurugan , Madden Daniel W. , Artiaga Bianca Libanori , Pogranichniy Roman M. , Sosa Gleyder Roman , Henningson Jamie , Wilson William C. , Balasuriya Udeni B. R. , García-Sastre Adolfo , Richt Juergen A. 
Published: August 2021

AbstractSARS-CoV-2, a novelBetacoronavirus, was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks (SARS-CoV and MERS-CoV) have demonstrated the significant role of intermediate and reservoir hosts in viral maintenance and transmission cycles. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, andin silicoandin vitrostudies have indicated that deer are susceptible to SARS-CoV-2 infection. White-tailed deer (Odocoileus virginianus) are amongst the most abundant, densely populated, and geographically widespread wild ruminant species in the United States. Human interaction with white-tailed deer has resulted in the occurrence of disease in human populations in the past. Recently, white-tailed deer fawns were shown to be susceptible to SARS-CoV-2. In the present study, we investigated the susceptibility and transmission of SARS-CoV-2 in adult white-tailed deer. In addition, we examined the competition of two SARS-CoV-2 isolates, representatives of the ancestral lineage A (SARS-CoV-2/human/USA/WA1/2020) and the alpha variant of concern (VOC) B.1.1.7 (SARS-CoV-2/human/USA/CA_CDC_5574/2020), through co-infection of white-tailed deer. Next-generation sequencing was used to determine the presence and transmission of each strain in the co-infected and contact sentinel animals. Our results demonstrate that adult white-tailed deer are highly susceptible to SARS-CoV-2 infection and can transmit the virus through direct contact as well as vertically from doe to fetus. Additionally, we determined that the alpha VOC B.1.1.7 isolate of SARS-CoV-2 outcompetes the ancestral lineage A isolate in white-tailed deer, as demonstrated by the genome of the virus shed from nasal and oral cavities from principal infected and contact animals, and from virus present in tissues of principal infected deer, fetuses and contact animals.
Immune competence and spleen size scale with colony status in the naked mole-rat
Authors: Bégay Valérie , Cirovic Branko , Barker Alison J. , Klopfleisch Robert , Hart Daniel W. , Bennett Nigel C. , Lewin Gary R. 
Published: August 2021

AbstractNaked mole-rats (NM-R;Heterocephalus glaber) live in multi-generational colonies with a social hierarchy, show low cancer incidence and long life-spans. Here we asked if such extreme physiology might have an immune component. The spleen is the largest lymphoid organ and plays an essential role in response to immunological insults and may participate in combating cancer and slowing ageing. We investigated the anatomy, molecular composition and function of the NM-R spleen using RNA-sequencing and histological analysis in healthy animals. We found that spleen size in healthy NM-Rs varies considerably. We therefore classified NM-Rs according to spleen size as NM-Rs with small spleens or enlarged spleens. Animals with enlarged spleens showed potentially better anti-microbial profiles and were much more likely to have a high rank within the colony. Splenomegaly was associated with infection in sick NM-Rs, but not in NM-Rs with enlarged spleens. In all healthy NM-Rs splenic erythropoiesis, megakaryopoiesis and myelopoiesis were increased, but B lymphopoiesis was reduced and splenic marginal zone showed markedly altered morphology when compared to other rodents. However, in NM-Rs lymphocytes were found in secondary sites such as lymph nodes, gut lymphoid nodules and thymus. Thus, the NM-R spleen is a major site of adult hematopoiesis under normal physiological conditions. Overall, the NM-R immune system seems to rely mainly on innate immune responses with a more restricted adaptive immune response. We propose that the anatomical plasticity of the spleen might be regulated by social interaction and gives immunological advantage to increase the life-span of higher ranked animals.
Musicians and non-musicians’ consonant/dissonant perception investigated by EEG and fMRI
Authors: Jo HanShin , Hsieh Tsung-Hao , Chien Wei-Che , Shaw Fu-Zen , Liang Sheng-Fu , Kung Chun-Chia 
Published: August 2021

AbstractThe perception of two (or more) simultaneous musical notes, depending on their pitch interval(s), could be broadly categorized as consonant or dissonant. Previous studies have suggested that musicians and non-musicians adopt different strategies when discerning music intervals: the frequency ratio (perfect fifth or tritone) for the former, and frequency differences (e.g., roughness vs. non-roughness) for the latter. To extend and replicate this previous finding, in this follow-up study we reran the ElectroEncephaloGraphy (EEG) experiment, and separately collected functional magnetic resonance imaging (fMRI) data of the same protocol. The behavioral results replicated our previous findings that musicians used pitch intervals and nonmusicians roughness for consonant judgments. And the ERP amplitude differences between groups in both frequency ratio and frequency differences were primarily around N1 and P2 periods along the midline channels. The fMRI results, with the joint analyses by univariate, multivariate, and connectivity approaches, further reinforce the involvement of midline and related-brain regions in consonant/dissonance judgments. Additional representational similarity analysis (or RSA), and the final spatio-temporal searchlight RSA (or ss-RSA), jointly combined the fMRI-EEG into the same representational space, providing final support on the neural substrates of neurophysiological signatures. Together, these analyses not just exemplify the importance of replication, that musicians rely more on top-down knowledge for consonance/dissonance perception; but also demonstrate the advantages of multiple analyses in constraining the findings from both EEG and fMRI.Significance StatementIn this study, the neural correlates of consonant and dissonant perception has been revisited with both EEG and fMRI. Behavioral results of the current study well replicated the pattern of our earlier work (Kung et al., 2014), and the ERP results, though showing that both musicians and nonmusicians processed rough vs. non-rough notes similarly, still supported the top-down modulation in musicians likely through long-term practice. The fMRI results, combining univariate (GLM contrast and functional connectivity) and multivariate (MVPA searchlight and RSA on voxel-, connectivity-, and spatio-temporal RSA searchlight-level) analyses, commonly speak to lateralized and midline regions, at different time windows, as the core brain networks that underpin both musicians’ and nonmusicians’ consonant/dissonant perceptions.
Rapid fluctuations in functional connectivity of cortical networks encode spontaneous
Authors: Benisty Hadas , Barson Daniel , Moberly Andrew H. , Lohani Sweyta , Coifman Ronald R. , Mishne Gal , Crair Michael C. , Cardin Jessica A. , Higley Michael J. 
Published: August 2021

AbstractExperimental work across a variety of species has demonstrated that spontaneously generated behaviors are robustly coupled to variation in neural activity within the cerebral cortex. Indeed, functional magnetic resonance imaging (fMRI) data suggest that functional connectivity in cortical networks varies across distinct behavioral states, providing for the dynamic reorganization of patterned activity. However, these studies generally lack the temporal resolution to establish links between cortical signals and the continuously varying fluctuations in spontaneous behavior typically observed in awake animals. Here, we took advantage of recent developments in wide-field, mesoscopic calcium imaging to monitor neural activity across the neocortex of awake mice. We develop a novel “graph of graphs” approach to quantify rapidly time-varying functional connectivity and show that spontaneous behaviors are represented by fast changes in both the activity and correlational structure of cortical network activity. Combining mesoscopic imaging with simultaneous cellular resolution 2-photon microscopy also demonstrated that the correlations among neighboring neurons and between local and large-scale networks also encodes behavior. Finally, the dynamic functional connectivity of mesoscale signals revealed subnetworks that are not predicted by traditional anatomical atlas-based parcellation of the cortex. These results provide new insight into how behavioral information is represented across the mammalian neocortex and demonstrate an analytical framework for investigating time-varying functional connectivity in neural networks.
DefectiveSlc7a7transport reduces erythropoietin compromising erythropoiesis and iron homeostasis
Authors: Giroud-Gerbetant Judith , Sotillo Fernando , Hernández Gonzalo , Lynch Cian J , Ruano Irene , Siri Barbara , Sebastian David , Zorzano Antonio , Artuch Rafael , Ormazabal Aida , Sánchez Mayka , Weiss Günter , Prats Neus , Dionisi-Vici Carlo , Serrano Manuel , Palacín Manuel , Bodoy Susanna 
Published: August 2021

AbstractLysinuric Protein Intolerance (LPI) is an inborn error of metabolism resulting fromSLC7A7deficiency that causes diminished plasma concentration of cationic amino acids. The clinical picture is highly heterogeneous among patients, who commonly present intolerance to protein intake and more severe complications such as hematological abnormalities and kidney failure. Although current treatments aim to address the metabolic defects of LPI, they have been unsatisfactory when treating the most severe symptoms. Here we show that the absence ofSlc7a7in mice causes iron overload as a result of erythropoiesis failure. Regarding iron metabolism, we demonstrate that reduced plasma erythropoietin triggers a strong iron overload, as erythropoietin administration restores normal iron levels and mitigate hematological alterations. Interestingly, we found that human LPI is associated with hyperferritinemia but not iron overload, a trait that might be influenced by the citrulline treatment. Furthermore, we show that erythropoietin is a key factor in the hematological abnormalities in LPI. Our study reveals a mechanism leading to LPI-induced hematological complications and identifies erythropoietin supplementation as a promising therapeutic strategy for human LPI.Significance StatementThe systemic metabolic environment derived fromSlc7a7-ablation in epithelial cells from kidney and intestine causes erythropoiesis failure prompting therefore iron overload. Here, we identify erythropoietin as the main driver of erythropoiesis failure as exogenous erythropoietin administration restores normal erythroblast population. In addition, we have also analyzed human data and found that patients with LPI have abnormal ferritin levels. Finally, as human LPI, citrulline treatment in mice restores normal iron homeostasis, highlighting the relevance of the systemic environment in LPI. Erythropoietin supplementation emerges as a promising therapeutic strategy for human LPI without the inflammatory effect associated with citrulline supplementation.
Local overfishing patterns have regional effects on health of coral, and economic transitions can promote its recovery
Authors: Milne Russell , Bauch Chris , Anand Madhur 
Published: August 2021

AbstractOverfishing has the potential to severely disrupt coral reef ecosystems worldwide, while harvesting at more sustainable levels instead can boost fish yield without damaging reefs. The dispersal abilities of reef species mean that coral reefs form highly connected environments, and the viability of reef fish populations depends on spatially explicit processes such as the spillover effect and unauthorized harvesting inside marine protected areas. However, much of the literature on coral conservation and management has only examined overfishing on a local scale, without considering how different spatial patterns of fishing levels can affect reef health both locally and regionally. Here, we simulate a coupled human-environment model to determine how coral and herbivorous reef fish respond to overfishing across multiple spatial scales. We find that coral and reef fish react in opposite ways to habitat fragmentation driven by overfishing, and that a potential spillover effect from marine protected areas into overfished patches helps coral populations far less than it does reef fish. We also show that ongoing economic transitions from fishing to tourism have the potential to revive fish and coral populations over a relatively short timescale, and that large-scale reef recovery is possible even if these transitions only occur locally. Our results show the importance of considering spatial dynamics in marine conservation efforts, and demonstrate the ability of economic factors to cause regime shifts in human-environment systems.
Polymer microparticles prolong delivery of the 15-PGDH inhibitor SW033291
Authors: Dogan Alan B. , Rohner Nathan A. , Smith Julianne N.P. , Kilgore Jessica A. , Williams Noelle S. , Markowitz Sanford D. , von Recum Horst A. , Desai Amar B. 
Published: August 2021

AbstractAs the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. While bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles – specifically β-CD microparticles (β-CD MPs) – to extend the delivery of 15-PGDH inhibitor, (+)SW033291, to over one week.Graphical Abstract
Prediction of coronavirus 3C-like protease cleavage sites using machine-learning algorithms
Authors: Chen Huiting , Zhu Zhaozhong , Qiu Ye , Ge Xingyi , Zheng Heping , Peng Yousong 
Published: August 2021

AbstractThe coronavirus 3C-like (3CL) protease is a Cysteine protease. It plays an important role in viral infection and immune escape by not only cleaving the viral polyprotein ORF1ab at 11 sites, but also cleaving the host proteins. However, there is still a lack of effective tools for determining the cleavage sites of the 3CL protease. This study systematically investigated the diversity of the cleavage sites of the coronavirus 3CL protease on the viral polyprotein, and found that the cleavage motif were highly conserved for viruses in the genera of Alphacoronavirus, Betacoronavirus and Gammacoronavirus. Strong residue preferences were observed at the neighboring positions of the cleavage sites. A random forest (RF) model was built to predict the cleavage sites of the coronavirus 3CL protease based on the representation of residues at cleavage site and neighboring positions by amino acid indexes, and the model achieved an AUC of 0.96 in cross-validations. The RF model was further tested on an independent test dataset composed of cleavage sites on host proteins, and achieved an AUC of 0.88 and a prediction precision of 0.80 when considering the accessibility of the cleavage site. Then, 1,079 human proteins were predicted to be cleaved by the 3CL protease by the RF model. These proteins were enriched in pathways related to neurodegenerative diseases and pathogen infection. Finally, a user-friendly online server named 3CLP was built to predict the cleavage sites of the coronavirus 3CL protease based on the RF model. Overall, the study not only provides an effective tool for identifying the cleavage sites of the 3CL protease, but also provides insights into the molecular mechanism underlying the pathogenicity of coronaviruses.
Variation in the strength of selection but no trait divergence between elevational extremes in a tropical rainforestDrosophila
Authors: O’Brien Eleanor K. , Higgie Megan , Saxon Andrew D. , Hoffmann Ary A. , Bridle Jon 
Published: August 2021

AbstractEvolutionary responses to environmental change require heritable variation in traits under selection. Both heritability and selection vary with the environment, and may also covary, so environmental variation can affect evolutionary rates. However, simultaneous estimates of heritability and selection across environmental gradients in the field are rare. We estimated environmental variation in selection on three traits (cold tolerance, heat tolerance, and wing size) of the rainforest fruitflyDrosophila birchii. We transplanted flies in cages along two elevational gradients in north-east Queensland, Australia, and calculated the genetic covariance of trait values with fitness (productivity in cages) at each site. For wing size, we estimated heritability at each site from the correlation between field-reared offspring and their laboratory-reared relatives. We used estimates of selection and heritability to predict selection responses along the elevation gradients, and compared these with trait variation observed in flies sourced from populations at elevational extremes. We found evidence for divergent selection on cold tolerance across elevation at one gradient. Heritability of wing size was highest at gradient ends, and the size of the predicted response to selection on this trait increased with elevation. However, the direction of selection varied, even among adjacent sites, making such selection unlikely to cause divergence of this trait with elevation. None of the traits differed between populations from elevational extremes at either gradient. Variation in the strength and direction of selection over small spatial scales, as well as in time, may explain why predicted responses to selection are often not seen in natural populations.
Magnetic Nanoprobes for Spatio-Mechanical Manipulation in Single Cells
Authors: Novoselova Iuliia P. , Neusch Andreas , Brand Julia-Sarita , Otten Marius , Safari Mohammad Reza , Bartels Nina , Karg Matthias , Farle Michael , Wiedwald Ulf , Monzel Cornelia 
Published: August 2021

AbstractMagnetic nanoparticles (MNPs) are widely known as valuable agents for biomedical applications. Yet, for their successful application within cells they need to fulfill a variety of demands such as monodispersity, biocompatibility or sufficient magnetic response. Given these prerequisites, MNPs may be used for remote, non-invasive manipulation, where their spatial redistribution or force response in a magnetic field provides a fine-tunable stimulus to a cell. Here, we investigate the properties of two different MNPs and their suitability for spatio-mechanical manipulations: semisynthetic magnetoferritin nanoparticles and fully synthetic ‘nanoflower’-shaped iron-oxide nanoparticles. Next to characterizing their structure, surface potential and magnetic response, we monitor the MNP performance in a living cell environment using fluorescence microscopy and confirm their biocompatibility. We then demonstrate their capability to spatially redistribute and to respond to magnetic force gradients inside a cell. Our remote manipulation assays present these tailored magnetic materials as suitable agents for applications in magnetogenetics, biomedicine or nanomaterial research.
Real-Time Search Assisted Acquisition on a Tribrid Mass Spectrometer Improves Coverage in Multiplexed Single-Cell Proteomics
Authors: Furtwängler Benjamin , Üresin Nil , Motamedchaboki Khatereh , Huguet Romain , Lopez-Ferrer Daniel , Zabrouskov Vlad , Porse Bo T. , Schoof Erwin M. 
Published: August 2021

ABSTRACTIn the young field of single-cell proteomics (scMS), there is a great need for improved global proteome characterization, both in terms of proteins quantified per cell and quantitative performance thereof. The recently introduced real-time search (RTS) on the Orbitrap Eclipse Tribrid mass spectrometer in combination with SPS-MS3 acquisition has been shown to be beneficial for the measurement of samples that are multiplexed using isobaric tags. Multiplexed single-cell proteomics requires high ion injection times and high-resolution spectra to quantify the single-cell signal, however the carrier channel facilitates peptide identification and thus offers the opportunity for fast on-the-fly precursor filtering before committing to the time intensive quantification scan. Here, we compared classical MS2 acquisition against RTS-SPS-MS3, both using the Orbitrap Eclipse Tribrid MS with the FAIMS Pro ion mobility interface and present a new acquisition strategy termed RETICLE (RTS Enhanced Quant of Single Cell Spectra) that makes use of fast real-time searched linear ion trap scans to preselect MS1 peptide precursors for quantitative MS2 Orbitrap acquisition. We show that classical MS2 acquisition is outperformed by both RTS-SPS-MS3 through increased quantitative accuracy at similar proteome coverage, and RETICLE through higher proteome coverage, with the latter enabling the quantification of over 1000 proteins per cell at a MS2 injection time of 750ms using a 2h gradient.
Drought exerts a greater influence than growth temperature on the temperature response of leaf day respiration in wheat (Triticum aestivum)
Authors: Fang Liang , Yin Xinyou , van der Putten Peter E. L. , Martre Pierre , Struik Paul C. 
Published: August 2021

AbstractWe assessed how the temperature response of leaf day respiration (Rd) in wheat responded to contrasting water regimes and growth temperatures. In Experiment 1, well-watered and drought-stressed conditions were imposed on two genotypes; in Experiment 2, the two water regimes combined with high (HT), medium (MT) and low (LT) growth temperatures were imposed on one of the genotypes. Rd was estimated from simultaneous gas exchange and chlorophyll fluorescence measurements at six leaf temperatures (Tleaf) for each treatment, using the Yin method for non-photorespiratory conditions and the non-rectangular hyperbolic fitting method for photorespiratory conditions. The two genotypes responded similarly to growth and measurement conditions. Estimates of Rd for non-photorespiratory conditions were generally higher than those for photorespiratory conditions but their responses to Tleaf were similar. Under well-watered conditions, Rd and its sensitivity to Tleaf slightly acclimated to LT but did not acclimate to HT. Temperature sensitivities of Rd were considerably suppressed by drought, and the suppression varied among growth temperatures. Thus, it is necessary to quantify interactions between drought and growth temperature for reliably modelling Rd under climate change. Our study also demonstrated that the Kok method, a currently popular method for estimating Rd, underestimated Rd significantly and should be abandoned.HighlightLeaf day respiration (Rd) acclimated little to growth temperature, but significantly to drought by reducing its thermal sensitivity. The Kok method underestimates Rd and should no longer be used.