bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tardigrades exhibit robust inter-limb coordination across walking speeds
Authors: Nirody Jasmine A , Duran Lisset A. , Johnston Deborah , Cohen Daniel J. 
Published: March 2021

AbstractTardigrades must negotiate heterogeneous, fluctuating environments, and accordingly utilize locomotive strategies capable of dealing with variable terrain. We analyze the kinematics and inter-leg coordination of freely walking tardigrades (species:Hypsibius dujardini). We find that tardigrade walking replicates several key features of walking in insects despite disparities in size, skeleton, and habitat. To test the effect of environmental changes on tardigrade locomotor control circuits, we measure kinematics and inter-leg coordination during walking on two substrates of different stiffnesses. We find that the phase offset between contralateral leg pairs is flexible, while ipsilateral coordination is preserved across environmental conditions. This mirrors similar results in insects and crustaceans. We propose that these functional similarities in walking co-ordination between tardigrades and arthropods is either due to a generalized locomotor control circuit common to panarthropods, or to independent convergence onto an optimal strategy for robust multi-legged control in small animals with simple circuitry. Our results highlight the value of tardigrades as a comparative system towards understanding the mechanisms – neural and/or mechanical – underlying coordination in panarthropod locomotion.
Membrane-MEDYAN: Simulating Deformable Vesicles Containing Complex Cytoskeletal Networks
Authors: Ni Haoran , Papoian Garegin A. 
Published: March 2021

AbstractThe plasma membrane defines the shape of the cell and plays an indispensable role in bridging intra- and extra-cellular environments. Mechanochemical interactions between plasma membrane and cytoskeleton are vital for cell biomechanics and mechanosensing. A computational model that comprehensively captures the complex, cell-scale cytoskeleton-membrane dynamics is still lacking. In this work, we introduce a triangulated membrane model that accounts for membrane’s elastic properties, as well as for membrane-filament steric interactions. The corresponding force-field was incorporated into the active biological matter simulation platform, MEDYAN (“Mechanochemical Dynamics of Active Networks”). Simulations using the new model shed light on how actin filament bundling affects generation of tubular membrane protrusions. In particular, we used membrane-MEDYAN simulations to investigate protrusion initiation and dynamics while varying geometries of filament bundles, membrane rigidities and local G-Actin concentrations. We found that bundles’ protrusion propensities sensitively depend on the synergy between bundle thickness and inclination angle at which the bundle approaches the membrane. The new model paves the way for simulations of biological systems involving intricate membrane-cytoskeleton interactions, such as occurring at the leading edge and the cortex, eventually helping to uncover the fundamental principles underlying the active matter organization in the vicinity of the membrane.
Critical interactions for SARS-CoV-2 spike protein binding to ACE2 identified by machine learning
Authors: Pavlova Anna , Zhang Zijian , Acharya Atanu , Lynch Diane L. , Pang Yui Tik , Mou Zhongyu , Parks Jerry M. , Chipot Chris , Gumbart James C. 
Published: March 2021

ABSTRACTBoth SARS-CoV and SARS-CoV-2 bind to the human ACE2 receptor. Based on high-resolution structures, the two viruses bind in practically identical conformations, although several residues of the receptor-binding domain (RBD) differ between them. Here we have used molecular dynamics (MD) simulations, machine learning (ML), and free energy perturbation (FEP) calculations to elucidate the differences in RBD binding by the two viruses. Although only subtle differences were observed from the initial MD simulations of the two RBD-ACE2 complexes, ML identified the individual residues with the most distinctive ACE2 interactions, many of which have been highlighted in previous experimental studies. FEP calculations quantified the corresponding differences in binding free energies to ACE2, and examination of MD trajectories provided structural explanations for these differences. Lastly, the energetics of emerging SARS-CoV-2 mutations were studied, showing that the affinity of the RBD for ACE2 is increased by N501Y and E484K mutations but is slightly decreased by K417N.
Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information
Authors: Rando Halie M. , Bennett Tellen D. , Byrd James Brian , Bramante Carolyn , Callahan Tiffany J. , Chute Christopher G. , Davis Hannah E. , Deer Rachel , Gagnier Joel , Koraishy Farrukh M , Liu Feifan , McMurry Julie A. , Moffitt Richard A. , Pfaff Emily R. , Reese Justin T. , Relevo Rose , Robinson Peter N. , Saltz Joel H. , Solomonides Anthony , Sule Anupam , Topaloglu Umit , Haendel Melissa A. 
Published: March 2021

AbstractSince late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely “Long COVID”, but also “COVID-19 syndrome (PACS)” or, “post-acute sequelae of SARS-CoV-2 infection (PASC)”. In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.
Water yield modelling, sensitivity analysis and validation: a study for Portugal
Authors: Almeida Bruna , Cabral Pedro 
Published: March 2021

AbstractThe spatially explicit assessment of freshwater is key to introduce the ecosystem service (ES) concept into decision-making processes. Many tools are being developed to model water balance and to analyse the effects of meteorological conditions on water ES behaviours at multiple spatial scales. Nevertheless, there is a lack of studies that analyse the sensitivity of these models and estimate the model’s accuracy. The current research uses the InVEST Water Yield Model (WYM) to assess freshwater ES between 1990 and 2018 at River Basin District (RBD) level in mainland Portugal. The methodology included sensitivity analysis simulations to test different parameters of the model over two different sources of meteorological data. We validated the model with the European Environment Agency (EEA) database on the quantity of Europe’s freshwater resources. To evaluate the models’ sensitivity, Pearson’s correlation coefficients and statistical methods were calculated for each simulation. The model which obtained the best performance in the sensitivity tests was retained for further analysis and calibration and its accuracy was assessed by comparing the mean estimated water yield (WY) with mean observed values for 2018. Results at the national level show a correlation coefficient of 0.803 with statistical significance for 0.01 one-tail. The WY in the RBDs of the North of the country was underestimated by 56.5 mm/ha/year and for the RBDs in the South of Portugal, the WY was overestimated by 58.1 mm/ha/year. This difference was explained through the spatial-temporal assessment of the main climatic variables used as input. This study contributes to a methodology to assess the level of confidence in WYM outputs and can be used to support the trustworthiness of water availability studies at sub-watershed, watershed, or RBD, using open access data and software.
Internal microbial zonation assists in the massive growth of marimo, a lake ball ofAegagropila linnaeiin Lake Akan
Authors: Nakai Ryosuke , Wakana Isamu , Niki Hironori 
Published: March 2021

AbstractMarimo (lake ball) is an uncommon ball-like aggregation of the green alga,Aegagropila linnaei.AlthoughA. linnaeiis broadly distributed in fresh and brackish waters in the northern hemisphere, marimo colonies are found only in particular habitats. The colonies have been gradually shrinking in recent years. Nevertheless, it is not clear how and whyA. linnaeiforms such massive spherical aggregations. Here, we report the bacterial microbiomes inside various sizes and aggregating structures of natural marimo collected from Lake Akan, Japan. We observed multi-layers composed of sediment particles only in the sizeable radial-type marimo with a >20 cm diameter, not in the tangled-type marimo. The deeper layers were enriched byNitrospira, potential novel sulphur-oxidizing bacteria, and sulphate-reducingDesulfobacteraceaebacteria. The sulphur cycle-related bacteria are unique to Lake Akan due to sulphur deposits from the nearby volcanic mountains. Some of them were also recovered from lake sediments. Microorganisms of the multi-layers would form biofilms incorporating nearby sediment, which would function as microbial “seals” within large radial-type marimo. We propose that the layer structure provides habitats for diverse bacterial communities, promotes airtightness of the marimo, and finally contributes to the massive growth of the aggregation. These findings provide a clue to deciphering the massive growth of endangered marimo aggregates.
The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells
Authors: Zhuang Xiaodong , Tsukuda Senko , Wrensch Florian , Wing Peter AC , Schilling Mirjam , Harris James M , Borrmann Helene , Morgan Sophie B , Cane Jennifer L , Mailly Laurent , Thakur Nazia , Conceicao Carina , Sanghani Harshmeena , Heydmann Laura , Bach Charlotte , Ashton Anna , Walsh Steven , Tan Tiong Kit , Schimanski Lisa , Huang Kuan-Ying A , Schuster Catherine , Watashi Koichi , Hinks Timothy SC , Jagannath Aarti , Vausdevan Sridhar R , Bailey Dalan , Baumert Thomas F , McKeating Jane A 
Published: March 2021

SUMMARYThe COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via Spike glycoprotein binding angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organism’s response to its environment and can regulate host susceptibility to virus infection. We demonstrate a circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with a synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Transcriptome analysis revealed that Bmal1 silencing induced a wide spectrum of interferon stimulated genes in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to dampen SARS-CoV-2 infection. Our study suggests new approaches to understand and improve therapeutic targeting of SARS-CoV-2.
A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories
Authors: Sias Ana C. , Morse Ashleigh K. , Wang Sherry , Greenfield Venuz Y. , Goodpaster Caitlin M. , Wrenn Tyler M. , Wikenheiser Andrew M. , Holley Sandra M. , Cepeda Carlos , Levine Michael S. , Wassum Kate M. 
Published: March 2021

ABSTRACTAdaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFC→BLA and BLA→lOFC pathways form a functional circuit regulating the encoding (lOFC→BLA) and subsequent use (BLA→lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.
Interferon Resistance of Emerging SARS-CoV-2 Variants
Authors: Guo Kejun , Barrett Bradley S. , Mickens Kaylee L. , Vladar Ezster K. , Morrison James H. , Hasenkrug Kim J. , Poeschla Eric M. , Santiago Mario L. 
Published: March 2021

AbstractThe emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and four major variants of concern. Our data reveal increased interferon resistance in emerging SARS-CoV-2 variants, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.Author SummaryIn less than 2 years since its spillover into humans, SARS-CoV-2 has infected over 220 million people, causing over 4.5 million COVID-19 deaths. High infection rates provided substantial opportunities for the virus to evolve, as variants with enhanced transmissibility, pathogenesis, and resistance to vaccine-elicited neutralizing antibodies have emerged. While much focus has centered on the Spike protein which the virus uses to infect target cells, mutations were also found in other viral proteins that might inhibit innate immune responses. Specifically, viruses encounter a potent innate immune response mediated by the interferons, two of which, IFNα2 and IFNβ, are being repurposed for COVID-19 treatment. Here, we compared the potency of human interferons against ancestral and emerging variants of SARS-CoV-2. Our data revealed increased interferon resistance in emerging SARS-CoV-2 strains that included the alpha, beta, gamma and delta variants of concern, suggesting a significant, but underappreciated role for innate immunity in driving the next phase of the COVID-19 pandemic.
Structural and energetic profiling of SARS-CoV-2 antibody recognition and the impact of circulating variants
Authors: Yin Rui , Guest Johnathan D. , Taherzadeh Ghazaleh , Gowthaman Ragul , Mittra Ipsa , Quackenbush Jane , Pierce Brian G. 
Published: March 2021

ABSTRACTThe SARS-CoV-2 pandemic highlights the need for a detailed molecular understanding of protective antibody responses. This is underscored by the emergence and spread of SARS-CoV-2 variants, including B.1.1.7, P1, and B.1.351, some of which appear to be less effectively targeted by current monoclonal antibodies and vaccines. Here we report a high resolution and comprehensive map of antibody recognition of the SARS-CoV-2 spike receptor binding domain (RBD), which is the target of most neutralizing antibodies, using computational structural analysis. With a dataset of nonredundant experimentally determined antibody-RBD structures, we classified antibodies by RBD residue binding determinants using unsupervised clustering. We also identified the energetic and conservation features of epitope residues and assessed the capacity of viral variant mutations to disrupt antibody recognition, revealing sets of antibodies predicted to effectively target recently described viral variants. This detailed structure-based reference of antibody RBD recognition signatures can inform therapeutic and vaccine design strategies.
Participation after childhood stroke: Is there a relationship with lesion size, motor function and manual ability?
Authors: Simon-Martinez Cristina , Kamal Sandeep , Frickmann Fabienne , Steiner Leonie , Slavova Nedelina , Everts Regula , Steinlin Maja , Grunt Sebastian 
Published: March 2021

AbstractBackgroundChildhood arterial ischemic stroke (AIS) is associated with significant morbidity with up to 50% of affected children developing hemiparesis. Hemiparesis is assumed to influence participation within the peer group, but it is unclear to what extent its severity affects participation in different areas of social life.MethodsThirteen children (mean age 9y6m) with AIS (6 without hemiparesis, 7 with hemiparesis) and 21 controls (mean age 9y8m) participated. We scored hemiparesis severity with hand strength asymmetry (pinch and grip strength), measured with a dynamometer. We assessed manual ability (ABILHAND-Kids), socioeconomic status (Family Affluence Scale) and participation (Participation and Environment Measure – Children and Youth). From structural MRI, we measured lesion size. We investigated differences in participation and its relationship with hemiparesis severity using non-parametric partial correlations (controlling for lesion size, manual ability, and socioeconomic status), interpreted as absent (r<0.25), weak (r=0.25-0.50), moderate (r=0.50-0.75) or strong (r>0.75). Analyses were performed in jamovi 1.6.3.ResultsChildren with AIS (with or without hemiparesis) showed reduced participation frequency at school (p<0.001), whilst participation at home and in the community resembled that of their peers. Severity of hemiparesis was moderately related to frequency and involvement at home and to involvement and desire for change in the community, although unrelated to school participation.ConclusionReduced participation in school life requires close attention in the follow-up of children with AIS - regardless of the severity of hemiparesis. Participation at home and in the community is related to hemiparesis severity and may be improved with participation-focused motor intervention strategies.HighlightsChildren with stroke participate less frequently at school but are equally involved.Decreased participation at school is not related to hemiparesis severity.Participation at home and in the community are related to hemiparesis severity.
Multiplex Antibody Analysis of IgM, IgA and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts
Authors: Dobaño Carlota , Alonso Selena , Vidal Marta , Jiménez Alfons , Rubio Rocío , Santano Rebeca , Barrios Diana , Tomas Gemma Pons , Melé Casas María , Hernández García María , Girona-Alarcón Mònica , Puyol Laura , Melero Natalia Rodrigo , Carolis Carlo , Garcia-Miquel Aleix , Bonet-Carne Elisenda , Claverol Joana , Cubells Marta , Fortuny Claudia , Fumadó Victoria , Codina Anna , Bassat Quique , Muñoz-Almagro Carmen , Fernández de Sevilla Mariona , Gratacós Eduard , Izquierdo Luis , García-García Juan José , Aguilar Ruth , Jordan Iolanda , Moncunill Gemma 
Published: March 2021

ABSTRACTCOVID-19 affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions.We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA and IgG antibodies against five SARS-CoV-2 spike (S) and nucleocapsid (N) antigens in the context of a contacts and infectivity longitudinal study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain.Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary.In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection. Saliva antibody detection could allow determining COVID-19 prevalence in pediatric populations, alternative to bleeding or nasal swab, and serological diagnosis following vaccination.