bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin
Authors: Mycroft-West Courtney J. , Su Dunhao , Pagani Isabel , Rudd Timothy R. , Elli Stefano , Gandhi Neha S. , Guimond Scott E. , Miller Gavin J. , Meneghetti Maria C. Z. , Nader Helena B. , Li Yong , Nunes Quentin M. , Procter Patricia , Mancini Nicasio , Clementi Massimo , Bisio Antonella , Forsyth Nicholas R. , Ferro Vito , Turnbull Jeremy E. , Guerrini Marco , Fernig David G. , Vicenzi Elisa , Yates Edwin A. , Lima Marcelo A. , Skidmore Mark A. 
Published: December 2020

AbstractThe dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-O or 6-O sulfate groups than on N-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.
Additional Heart Sounds–Part 2 (Clicks, Opening Snap and More)
Authors: Nemani Lalita , Pechetty Ramya 
Published: December 2020

Abstract
Systolic clicks are high-pitched sharp sounds. They are classified as ejection and nonejection clicks. Ejections clicks commonly occur at the aortic and pulmonary valve, while nonejection clicks occur at the mitral and tricuspid valve.
Opening snap is an additional sound heard in the diastole. It is described as an early diastolic, high-pitched sound, which is associated with opening of the mitral and/or tricuspid valve.
Pericardial knock is a high-pitched early diastolic sound, which is characteristic of constrictive pericarditis.
The opening and closing of prosthetic valves produce sounds which may vary in intensity and timing according to the type and design of the valve, patient’s rhythm, and hemodynamic status.
Downregulation of autophagy by Met30-mediated Atg9 ubiquitination
Authors: Feng Yuchen , Ariosa Aileen R. , Yang Ying , Hu Zehan , Dengjel Jörn , Klionsky Daniel J. 
Published: December 2020

Significance
Macroautophagy/autophagy removes surplus and/or dysfunctional cellular components for recycling in the lysosome/vacuole. During times of stress, autophagy is upregulated to ensure survival. A set of autophagy-related (Atg) proteins act in concert in a highly regulated manner to ensure proper levels of autophagy; aberrant induction of this process is correlated with numerous diseases. In this work, we show a nuanced mechanism by which autophagy is kept at a basal level via the ubiquitin−proteasome system-dependent reduction of Atg9, a transmembrane protein essential to autophagy.
Concerns for others increase the likelihood of vaccination against influenza and COVID-19 more in sparsely rather than densely populated areas
Authors: Jung Haesung , Albarracín Dolores 
Published: December 2020

SignificanceVaccination yields the prosocial benefits of preventing the spread of infectious diseases and protecting communities from major disease outbreaks. This research examines how focusing on prosocial concerns motivates vaccination across environments with varying levels of social density. Contrary to the common intuition that prosocial concern should motivate vaccination more in denser areas with more social contacts and disease transmission risk, our results show that prosocial concern yields higher vaccination rates in sparser areas where people believe that their behavior will have more impact. This research identifies emphasizing prosocial aspects of vaccination as one means by which public health interventions can reduce the rural−urban disparity in vaccination.
Knockout of the HMG domain of the porcine SRY gene causes sex reversal in gene-edited pigs
Authors: Kurtz Stefanie , Lucas-Hahn Andrea , Schlegelberger Brigitte , Göhring Gudrun , Niemann Heiner , Mettenleiter Thomas C. , Petersen Björn 
Published: December 2020

Significance
The present work characterizes the porcine sex-determining region on the Y chromosome (SRY) gene and demonstrates its pivotal role in sex determination. We provide evidence that genetically male pigs with a knockout of the SRY gene undergo sex reversal of the external and internal genitalia. This discovery of SRY as the main switch for sex determination in pigs may provide an alternative for surgical castration in pig production, preventing boar taint. As the pig shares many genetic, physiological, and anatomical similarities with humans, it also provides a suitable large animal model for human sex reversal syndromes, allowing for the development of new interventions for human sex disorders.
DNA polymerase ι compensates for Fanconi anemia pathway deficiency by countering DNA replication stress
Authors: Wang Rui , Lenoir Walter F. , Wang Chao , Su Dan , McLaughlin Megan , Hu Qianghua , Shen Xi , Tian Yanyan , Klages-Mundt Naeh , Lynn Erica , Wood Richard D. , Chen Junjie , Hart Traver , Li Lei 
Published: December 2020

Significance
Pol ι is a highly conserved Y-family DNA polymerase. Disruptions of the Pol ι gene in cellular and mouse models, however, have so far failed to produce any detectable phenotype. Using unbiased whole genome fitness screens, we find that Pol ι is essential for the genome stability and survival of Fanconi anemia mutant cells. This finding reveals the physiological role for Pol ι as a compensatory factor of Fanconi anemia deficiency. It implies a novel genetic connection between lesion bypass and replication stress response. Furthermore, the identified synthetic lethality between Pol ι and the Fanconi anemia mechanism suggests an enzymatic and therapeutic target for eliminating tumor cells arising from the Fanconi anemia pathway defect.
Post-transcriptional tuning of FGF signaling mediates neural crest induction
Authors: Copeland Jacqueline , Simoes-Costa Marcos 
Published: December 2020

SignificanceThe neural crest is a stem cell population that plays a crucial role in the establishment of the vertebrate body plan. Neural crest induction requires a delicate balance of multiple signaling systems, including FGFs. Moderate FGF activity is necessary for neural crest formation, but overactivation of the pathway drives progenitor cells into adopting a neuronal fate. Yet, it remains unclear how levels of FGF are fine tuned to promote neural crest identity. Here, we demonstrate how miRNA-mediated gene silencing modulates the intracellular response to FGF signaling to ensure proper neural crest cell specification. Understanding the function of these miRNAs may broaden our understanding of the neural crest genetic program and shed light on the etiology of neural crest-linked congenital disabilities.
Prioritized experience replays on a hippocampal predictive map for learning
Authors: Igata Hideyoshi , Ikegaya Yuji , Sasaki Takuya 
Published: December 2020

Significance
The hippocampus is crucial for spatial learning but their neuronal mechanisms remain unknown. Here, we found that hippocampal cell ensembles preferentially replayed salient reward-related locations as rats learned a new behavioral trajectory for reward. The contents of these hippocampal replays progressively varied with learning. Especially during learning, hippocampal neurons even replayed an optimized path that had never been exploited by the animals. The learning-related hippocampal activity was necessary for the stabilization of spatial behavior. These results suggest prioritized replays of significant experiences on a predictive map by hippocampal neurons.
Microrheology reveals microscale viscosity gradients in planktonic systems
Authors: Guadayol Òscar , Mendonca Tania , Segura-Noguera Mariona , Wright Amanda J. , Tassieri Manlio , Humphries Stuart 
Published: December 2020

SignificanceAt the microscopic scales at which the life of marine microbes unfolds, the physics is dominated by viscosity. Increasing viscosity slows down both the passive transport of solutes and particles and the swimming of motile microorganisms, and thus directly or indirectly affects all aspects of microbial life. Viscosity depends not only on the physical properties of water, but it also varies as a consequence of biological activity, allowing microorganisms some control over their physical landscape. Our use of microrheology allows us to explore how viscosity is structured around phytoplankton cells and marine aggregates and unveils a level of spatial heterogeneity that has implications for the functioning of the microbial food web and hence of marine biogeochemical cycles.
Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment
Authors: Constantin Stephanie , Reynolds Daniel , Oh Andrew , Pizano Katherine , Wray Susan 
Published: December 2020

SignificanceHypothalamic neural networks control hormone secretion to maintain body function. For gonadotropin-releasing hormone (GnRH) neurons, critical to fertility, release must be pulsatile. While it is clear that kisspeptin neurons trigger GnRH activity and pulses, how GnRH neurons return to baseline activity before the next stimulation is unknown. Here, we show 1) that the long-lasting response of GnRH neurons to kisspeptin depends on the degradation of phosphatidylinositol 4,5-bisphosphate (PIP2) and its slow resynthesis keeping canonical transient receptor potential channels opened and 2) a mechanism whereby nitric oxide facilitates PIP2resynthesis and GnRH neuron recovery from kisspeptin activation. Defining the overlap in kisspeptin and nitric oxide signaling pathways may provide an avenue for fertility treatment.
Endoplasmic reticulum membrane receptors of the GET pathway are conserved throughout eukaryotes
Authors: Asseck Lisa Yasmin , Mehlhorn Dietmar Gerald , Monroy Jhon Rivera , Ricardi Martiniano Maria , Breuninger Holger , Wallmeroth Niklas , Berendzen Kenneth Wayne , Nowrousian Minou , Xing Shuping , Schwappach Blanche , Bayer Martin , Grefen Christopher 
Published: December 2020

SignificanceThe GET pathway is required for the insertion of tail-anchored (TA) membrane proteins in the endoplasmic reticulum (ER) of yeast and mammals. Some orthologous genes had also been identified in higher plants with the exception of one of the two ER membrane receptors required for membrane insertion. Get2/CAML is required for the pathway’s cytosolic chaperone to dock and release its TA protein cargo. Here we report the identification of the elusive plant GET pathway receptor through an interaction screen inArabidopsis. The candidate allows detection of further Get2/CAML orthologs in higher plants, revealing conservation and function of structural features across kingdoms. Additionally, our results demonstrate that these features, rather than sequence conservation, determine functionality of the candidate within the pathway.
Evaluating sustainable development policies in rural coastal economies
Authors: Lindsay Amanda R. , Sanchirico James N. , Gilliland Ted E. , Ambo-Rappe Rohani , Taylor J. Edward , Krueck Nils C. , Mumby Peter J. 
Published: December 2020

Significance
Support for marine-based “blue growth” policies derives from their potential to simultaneously address United Nations Sustainable Development (SD) Goals on poverty alleviation and marine conservation. Modeling the linkages between a rural coastal economy and local fish resources, this work provides a rigorous ex ante assessment of common strategies to achieve SD objectives. We find that most of the considered policies increase target household incomes, negatively impact some nontarget households, and further deplete nearshore fish stocks. The results underscore the importance of considering characteristics of local economies and household linkages to marine and land resources when designing SD policies to avoid unintended consequences.
Social isolation uncovers a circuit underlying context-dependent territory-covering micturition
Authors: Hyun Minsuk , Taranda Julian , Radeljic Gianna , Miner Lauren , Wang Wengang , Ochandarena Nicole , Huang Kee Wui , Osten Pavel , Sabatini Bernardo L. 
Published: December 2020

Significance
Vertebrates control the release of urine to mediate physiological functions as well as for social communication. The release of urine, or micturition, is controlled by the brain and is influenced by many internal and external factors. In mice, these include social standing, sensory context, and past experience as well as the state of the bladder. We study the brain circuits that control micturition in mice and uncover pathways by which the patterns of urine release are altered in response to changes in social experience and olfactory stimuli.
Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus
Authors: Wang Ye , Fu Wing-Yu , Cheung Kit , Hung Kwok-Wang , Chen Congping , Geng Hongyan , Yung Wing-Ho , Qu Jianan Y. , Fu Amy K. Y. , Ip Nancy Y. 
Published: December 2020

Significance
Synaptic plasticity in the hippocampus is important for learning and memory formation. In particular, homeostatic synaptic plasticity enables neurons to restore their activity levels in response to chronic neuronal activity changes. While astrocytes modulate synaptic functions via the secretion of factors, the underlying molecular mechanisms remain unclear. Here, we show that suppression of hippocampal neuronal activity increases cytokine IL-33 release from astrocytes in the CA1 region. Activation of IL-33 and its neuronal ST2 receptor complex promotes functional excitatory synapse formation. Moreover, IL-33/ST2 signaling is important for the neuronal activity blockade-induced increase of CA1 excitatory synapses in vivo and spatial memory formation. This study suggests that astrocyte-secreted IL-33 acts as a negative feedback control signal to regulate hippocampal homeostatic synaptic plasticity.
Adipose tissue is a critical regulator of osteoarthritis
Authors: Collins Kelsey H. , Lenz Kristin L. , Pollitt Eleanor N. , Ferguson Daniel , Hutson Irina , Springer Luke E. , Oestreich Arin K. , Tang Ruhang , Choi Yun-Rak , Meyer Gretchen A. , Teitelbaum Steven L. , Pham Christine T. N. , Harris Charles A. , Guilak Farshid 
Published: December 2020

Significance
Obesity is a primary risk factor for osteoarthritis, involving complex interactions among the metabolic, biomechanical, and inflammatory factors caused by increased adiposity. Using a mouse model of lipodystrophy, we demonstrate that fat-free mice on either a chow or high-fat diet are protected from cartilage damage, despite demonstrating many factors previously associated with osteoarthritis. Furthermore, implantation of a small fat pad reverses cartilage protection in lipodystrophic mice, indicating a direct relationship between adipose tissue and cartilage damage, independent of body weight. This study provides evidence of adipose–cartilage signaling, indicating that tissues outside the joint can influence cartilage health. These findings support the notion that osteoarthritis involves a systemic component, providing insight into the development of new therapeutic targets for osteoarthritis.
Discovering multiscale and self-similar structure with data-driven wavelets
Authors: Floryan Daniel , Graham Michael D. 
Published: December 2020

Significance
Multiscale structure is all around us: in biological tissues, active matter, oceans, networks, and images. Identifying the multiscale features of these systems is crucial to our understanding and control of them. We introduce a method that rationally extracts localized multiscale features from data, which may be thought of as the building blocks of the underlying phenomena.
A phosphorylation-dependent switch in the disordered p53 transactivation domain regulates DNA binding
Authors: Sun Xun , Dyson H. Jane , Wright Peter E. 
Published: December 2020

Significance
The transcription factor p53 is a master tumor suppressor that controls the cellular response to genotoxic stress. Following DNA damage, p53 is activated by phosphorylation at multiple sites in the intrinsically disordered N-terminal transactivation domain. In particular, the phosphorylation status of Thr55 controls both activation and termination of p53-mediated transcriptional programs during different stages of the cellular DNA damage response. Here we show that Thr55 functions as a phosphorylation-dependent regulatory switch that modulates synergistic intramolecular interactions between the disordered transactivation domain and the structured DNA-binding domain. The strength of these interactions is fine-tuned by the intervening proline-rich domain and is enhanced by Thr55 phosphorylation, resulting in autoinhibition of p53 binding to promoters that regulate cell cycle arrest and apoptosis.
Quantum stability of generalized Proca theories
Authors: Heisenberg Lavinia , Zosso Jann 
Published: December 2020

Abstract
We establish radiative stability of generalized Proca effective field theories. While standard power-counting arguments would conclude otherwise, we find non-trivial cancellations of leading order corrections by explicit computation of divergent one-loop diagrams up to four-point. These results are crosschecked against an effective action based generalized Schwinger–DeWitt method. Further, the cancellations are understood as coming from the specific structure of the theory through a decoupling limit analysis which at the same time allows for an extension of the results to higher orders.
Real-time HCl gas detection at parts-per-billion level concentrations utilising a diode laser and a bismuth-doped fibre amplifier
Authors: Panu Hildén , Timo Rajamäki , Thomas Fordell , Makkonen Jarkko , Alyshev Sergei , Kharakhordin Alexandr , Firstov Sergei 
Published: December 2020

Abstract
HCl measurements in a cleanroom environment are carried out using a cavity ring-down analyser in order to get an estimate of the HCl concentrations that can be expected to be present in semiconductor manufacturing. HCl is a reactive gas and the materials used for gas sampling and transportation have a significant effect on the measurement response time; hence, data on HCl adsorption to different materials is also provided. Finally, a light source operating at 1742 nm that can be used for HCl detection in a multi-gas analyser based on multipass photo-acoustic spectroscopy is presented. Preliminary results indicate that sub-ppb detection levels are achievable using this approach even for HCl.
Engineering SnO2 nanorods/ethylenediamine-modified graphene heterojunctions with selective adsorption and electronic structure modulation for ultrasensitive room-temperature NO2 detection
Authors: Zheng Shengliang , Sun Jianyong , Hao Juanyuan , Sun Quan , Wan Peng , Li Yue , Zhou Xin , Yuan Ye , Zhang Xu , Wang You 
Published: December 2020

Abstract
Ever-increasing concerns over air quality and the newly emerged internet of things (IoT) for future environmental monitoring are stimulating the development of ultrasensitive room-temperature gas sensors, especially for nitrogen dioxide (NO2), one of the most harmful air pollution species released round-the-clock from power plants and vehicle exhausts. Herein, tin dioxide nanorods/ethylenediamine-modified reduced graphene oxide (SnO2/EDA-rGO) heterojunctions with selective adsorption and electronic structure modulation were engineered for highly sensitive and selective detection of NO2 at room temperature. The modified EDA groups not only enable selective adsorption to significantly enrich NO2 molecules around the interface but also realize a favorable modulation of SnO2/EDA-rGO electronic structure by increasing the Fermi level of rGO, through which the sensing performance of NO2 is synergistically enhanced. The response of the SnO2/EDA-rGO sensor toward 1 ppm NO2 reaches 282%, which exceeds the corresponding SnO2/rGO sensor by a factor of 2.8. It also exhibits a low detection limit down to 100 ppb, enhanced selectivity, and rapid response/recovery kinetics. This approach to designing a novel heterojunction with significantly enhanced chemical and electric effects may shed light on the future engineering of gas-sensing materials.
Deep learning-augmented radiotherapy visualization with a cylindrical radioluminescence system
Authors: Jia Mengyu , Li Xiaomeng , Wu Yan , Yang Yong , Kasimbeg Priya , Skinner Lawrie , Wang Lei , Xing Lei 
Published: December 2020

Abstract
This study aims to demonstrate a low-cost camera-based radioluminescence imaging system (CRIS) for high-quality beam visualization that encourages accurate pre-treatment verifications on radiation delivery in external beam radiotherapy. To ameliorate the optical image that suffers from mirror glare and edge blurring caused by photon scattering, a deep learning model is proposed and trained to learn from an on-board electronic portal imaging device (EPID). Beyond the typical purposes of an on-board EPID, the developed system maintains independent measurement with co-planar detection ability by involving a cylindrical receptor. Three task-aware modules are integrated into the network design to enhance its robustness against the artifacts that exist in an EPID running at the cine mode for efficient image acquisition. The training data consists of various designed beam fields that were modulated via the multi-leaf collimator (MLC). Validation experiments are performed for five regular fields ranging from 2 × 2 cm2 to 10 × 10 cm2 and three clinical IMRT cases. The captured CRIS images are compared to the high-quality images collected from an EPID running at the integration-mode, in terms of gamma index and other typical similarity metrics. The mean 2%/2 mm gamma pass rate is 99.14% (range between 98.6% and 100%) and 97.1% (ranging between 96.3% and 97.9%), for the regular fields and IMRT cases, respectively. The CRIS is further applied as a tool for MLC leaf-end position verification. A rectangular field with introduced leaf displacement is designed, and the measurements using CRIS and EPID agree within 0.100 mm ± 0.072 mm with maximum of 0.292 mm. Coupled with its simple system design and low-cost nature, the technique promises to provide viable choice for routine quality assurance in radiation oncology practice.