bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personalization of mathematical models of human atrial action potential
Authors: Pikunov Andrey V. , Syunyaev Roman A. , Steckmeister Vanessa , Kutschka Ingo , Voigt Niels , Efimov Igor R. 
Published: June 2020

AbstractAtrial cardiomyocytes demonstrate a wide spectrum of patient-specific, tissue-specific, and pathology-specific action potential (AP) phenotypes due to differences in protein expression and posttranslational modifications. Accurate simulation of the AP excitation and propagation in healthy or diseased atria requires a mathematical model capable of reproducing all the differences by parameter rescaling. In the present study, we have benchmarked two widely used electrophysiological models of the human atrium: the Maleckar and the Grandi models. In particular, patch-clamp AP recordings from human atrial myocytes were fitted by the genetic algorithm (GA) to test the models' versatility. We have shown that the Maleckar model results in a more accurate fitting of heart rate dependence of action potential duration (APD) and resting potential (RP). On the other hand, both models demonstrate the poor fitting of the plateau phase and spike-and-dome morphologies. We propose that modifications to L-type calcium current-voltage relationships are required to improve atrial models' fidelity.
SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity
Authors: Petruk Ganna , Puthia Manoj , Petrlova Jitka , Strömdahl Ann-Charlotte , Kjellström Sven , Schmidtchen Artur 
Published: June 2020

ABSTRACTThere is a well-known and established link between high lipopolysaccharide (LPS) levels in blood and the metabolic syndrome (MS). MS is a risk factor for developing severe COVID-19 and acute respiratory distress syndrome (ARDS). Here we define an interaction between SARS-CoV-2 Spike (S) protein and LPS and its link to aggravated inflammation in vitro and in vivo. Electrophoresis under native conditions demonstrated that SARS-CoV-2 S protein binds toEscherichia coliLPS, forming high molecular weight aggregates. Microscale thermophoresis analysis further defined the interaction, having a KDof ~47 nM, similar to the observed affinity between LPS and the human receptor CD14. Moreover, S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) and cytokine responses in monocytic THP-1 cells and human blood, respectively. In an experimental model of localized inflammation, employing NF-κB reporter mice and in vivo bioimaging, S protein in conjunction with LPS significantly increased the inflammatory response when compared with S protein and LPS alone. Apart from providing information on LPS as a ligand for S protein, our results are of relevance for studies on comorbidities involving bacterial endotoxins, such as the MS, or co-existing acute and chronic infections in COVID-19 patients.
CoExp Web, a web tool for the exploitation of co-expression networks
Authors: García-Ruiz Sonia , Gil-Martínez Ana L. , Cisterna Alejandro , Jurado-Ruiz Federico , Reynolds Regina R. ,   NABEC (North America Brain Expression Consortium), Cookson Mark R. , Hardy John , Ryten Mina , Botía Juan A. 
Published: June 2020

AbstractSummaryThis paper presents the CoExp Web tool. CoExp is a software tool and a Web resource that fosters research on co-expression network models by providing a highly usable means to exploit and share multiple network models.Availability and Implementationthe Web resource is accessible athttps://snca.atica.um.es/coexp/. The software at the front and back-ends is accessible athttps://github.com/SoniaRuiz/CoExp_Web.Contactskgtsg0@ucl.ac.uk(Sonia García-Ruíz)
Unique Proteomes Implicate Functional Specialization across Heterocysts, Akinetes, and Vegetative Cells inAnabaena cylindrica
Authors: Qiu Yeyan , Gu Liping , Brözel Volker , Whitten Douglas , Hildreth Michael , Zhou Ruanbao 
Published: June 2020

ABSTRACTIn response to environmental changes, vegetative cells ofAnabaena cylindricacan differentiate into two other cell types: a heterocyst for oxic N2-fixation, and an enlarged spore called akinete for stress survival. Akinetes normally differentiate from vegetative cells adjacent to heterocysts. Heterocysts inhibit nearby cells from differentiating into heterocysts but can induce adjacent cells to become akinetes, a rare embryogenetic induction in prokaryotes. The mechanism for a patterned differentiation inA. cylindricahas been little studied. Here, we isolated three types of cells fromA. cylindricato identify their proteomes using LC-MS/MS.A total of 1395 proteins were identified, including 664 proteins from akinetes, 751 proteins from heterocysts, and 1236 proteins from vegetative cells. There were 45 proteins (33 novel proteins) found exclusive to akinetes, 57 heterocyst-specific proteins (33 novel proteins), includingnifgene products, and 485 proteins exclusively in vegetative cells. Our proteomic data suggest that akinetes, unlike the typical spores of bacteria, perform unique biochemical functions that collaborate with both heterocysts and vegetative cells. A HAVe model for collaboration among heterocysts, akinetes and vegetative cells is proposed to illustrate the metabolic network of cyanophycin and carbohydrates based on the distribution of their biosynthesis related proteins in three types of cells. Interestingly, cell division proteins, DNA replication proteins, some carboxysomal proteins including RuBisCO and proteins in photosystems I, II were found abundant in heterocysts, the non-dividing cells dedicated exclusively to oxic N2-fixation. The identification of the akinete and heterocyst proteomes enables the pursuit of genetic studies into the patterned differentiation of akinetes and heterocysts.
Bursting out: linking changes in nano-topography and biomechanical properties of biofilm-forming Escherichia coli to T4 lytic cycle
Authors: Abraham Shiju , Kaufman Yair , Perreault François , Young Ry , Bar-Zeev Edo 
Published: June 2020

ABSTRACTBacteriophage infection cycle has been extensively studied, yet little is known on the structural and mechanical changes that lead to bacterial lysis. Here, bio-atomic force microscopy was used to study in real-time andin-situthe impact of the canonical phage T4 on the nano-topography and biomechanics of irreversibly attached, biofilm-formingE. colicells. The results show that in contrast to the lytic cycle in planktonic cells, which ends explosively, anchored cells that are in the process of forming biofilms undergo gradual lysis, developing distinct sub-micron lesions (∼300 nm in diameter) within the cell envelope. Furthermore, it is shown that the envelope rigidity and cell elasticity decrease (>50% and >40%, respectively) following T4 infection. These new insights show that the well-established lytic pathway of planktonic cells may be significantly different from that of biofilm-forming cells. Elucidating the lysis paradigm of these cells may advance biofilm removal and phage therapeutic.There is no conflict of interest and all co-authors have seen and approved the current version for submission.
Cellular logics bringing the symmetry breaking in spiral nucleation revealed by trans-scale imaging
Authors: Kakizuka Taishi , Hara Yusuke , Ohta Yusaku , Mukai Asuka , Ichiraku Aya , Arai Yoshiyuki , Ichimura Taro , Nagai Takeharu , Horikawa Kazuki 
Published: June 2020

SummaryThe spiral wave is a commonly observed spatio-temporal order in diverse signal relaying systems. Although properties of generated spirals have been well studied, the mechanisms for their spontaneous generation in living systems remain elusive. By the newly developed imaging system for trans-scale observation of the intercellular communication among ∼130,000 cells of social amoeba, we investigated the onset dynamics of cAMP signaling and identified mechanisms for the self-organization of the spiral wave at three distinct scalings: At the population-level, the structured heterogeneity of excitability fragments traveling waves at its high/low boundary, that becomes the generic source of the spiral wave. At the cell-level, both the pacemaking leaders and pulse-amplifying followers regulate the heterogeneous growth of the excitability. At the intermediate-scale, the essence of the spontaneous wave fragmentation is the asymmetric positioning of the pacemakers in the high-excitability territories, whose critical controls are operated by a small number of cells, pulse counts, and pulse amounts.
Grad-seq shines light on unrecognized RNA and protein complexes in the model bacteriumEscherichia coli
Authors: Hör Jens , Di Giorgio Silvia , Gerovac Milan , Venturini Elisa , Förstner Konrad U. , Vogel Jörg 
Published: June 2020

ABSTRACTStable protein complexes, including those formed with RNA, are major building blocks of every living cell.Escherichia colihas been the leading bacterial organism with respect to global protein-protein networks. Yet, there has been no global census of RNA/protein complexes in this model species of microbiology. Here, we performed Grad-seq to establish an RNA/protein complexome, reconstructing sedimentation profiles in a glycerol gradient for ~85% of allE. colitranscripts and ~49% of the proteins. These include the majority of small noncoding RNAs (sRNAs) detectable in this bacterium as well as the general sRNA-binding proteins, CsrA, Hfq and ProQ. In presenting use cases for utilization of these RNA and protein maps, we show that a stable association of RyeG with 30S ribosomes gives this seemingly noncoding RNA of prophage origin away as an mRNA of a toxic small protein. Similarly, we show that the broadly conserved uncharacterized protein YggL is a 50S subunit factor in assembled 70S ribosomes. Overall, this study crucially extends our knowledge about the cellular interactome of the primary model bacteriumE. colithrough providing global RNA/protein complexome information and should facilitate functional discovery in this and related species.
Decoding herbal materials of representative TCM preparations with the multi-barcoding approach
Authors: Yao Qi , Zhu Xue , Han Maozhen , Chen Chaoyun , Li Wei , Bai Hong , Ning Kang 
Published: June 2020

AbstractWith the rapid development of high-throughput sequencing (HTS) technology, the techniques for the assessment of biological ingredients in Traditional Chinese Medicine (TCM) preparations have also advanced. By using HTS together with the multi-barcoding approach, all biological ingredients could be identified from TCM preparations in theory, as long as their DNA is present. The biological ingredients of a handful of classical TCM preparations were analyzed successfully based on this approach in previous studies. However, the universality, sensitivity and reliability of this approach used on TCM preparations remain unclear. Here, four representative TCM preparations, namely Bazhen Yimu Wan, Da Huoluo Wan, Niuhuang Jiangya Wan and You Gui Wan, were selected for concrete assessment of this approach. We have successfully detected from 77.8% to 100% prescribed herbal materials based on both ITS2 andtrnLbiomarkers. The results based on ITS2 have also shown a higher level of reliability than those oftrnLat species level, and the integration of both biomarkers could provide higher sensitivity and reliability. In the omics big-data era, this study has undoubtedly made one step forward for the multi-barcoding approach for prescribed herbal materials analysis of TCM preparation, towards better digitization and modernization of drug quality control.
Visuomotor temporal adaptation is tuned to gamma brain oscillatory coherence
Authors: Cámara Clara , de la Malla Cristina , Marco-Pallarés Josep , López-Moliner Joan 
Published: June 2020

ABSTRACTEvery time we use our smartphone, tablet, or other electronic devices we are exposed to temporal delays between our actions and the sensory feedback. We can compensate for such delays by adjusting our motor commands and doing so likely requires establishing new temporal mappings between motor areas and sensory predictions. However, little is known about the neural underpinnings that would support building new temporal correspondences between different brain areas. We here address the possibility that communication through coherence, which is thought to support neural interareal communication, lies behind the neural processes accounting for how humans cope with additional delays between motor and sensory areas. We recorded EEG activity while participants intercepted moving targets while seeing a cursor that followed their hand with a delay rather than their own hand. Participants adjusted their movements to the delayed visual feedback and intercepted the target with the cursor. The EEG data shows a significant increase in coherence of beta and gamma bands between visual and motor areas during the hand on-going movement towards interception. However, when looking at differences between participants depending on the level of adaptation, only the increase in gamma band correlated with the level of temporal adaptation. We are able to describe the time course of the coherence using coupled oscillators showing that the times at which high coherence is achieved are within useful ranges to solve the task. Altogether, these results evidence the functional relevance of brain coherence in a complex task where adapting to new delays is crucial.AUTHOR SUMMARYHumans are often exposed to delays between their actions and the incoming sensory feedback caused by actions. While there have been advances in the understanding of the conditions at which temporal adaptation can occur, little is known about the neural mechanisms enabling temporal adaptation. In the present study we measure brain activity (EEG) to investigate whether communication through coherence between motor and sensory areas might be responsible for one’s ability to cope with externally imposed delays in an interception task. We show evidence that neural coherence at gamma band between visual and motor areas is related to the degree of adaptation to temporal delays.
Domain Binding and Isotype Dictate the Activity of Anti-human OX40 Antibodies
Authors: Griffiths Jordana , Hussain Khiyam , Smith Hannah L , Sanders Theodore , Cox Kerry , Semmrich Monika , Martensson Linda , Kim Jinny , Inzhelevskaya Tatyana , Penfold Chris , Tutt Alison L , Mockridge Ian M , Chan Claude HT , English Vikki , French Ruth R , Teige Ingrid , Al-Shamkhani Aymen , Glennie Martin J , Frendeus Bjorn , Willoughby Jane E , Cragg Mark S 
Published: June 2020

AbstractPrevious data suggests that anti-OX40 mAb can elicit anti-tumour effects in mice through deletion of Tregs. However, OX40 also has powerful costimulatory effects on T cells which could evoke therapeutic responses. The contributions of these different effector mechanisms has not previously been systematically evaluated, particularly for mAb directed to human OX40. Therefore, we generated a novel human OX40 knock-in (KI) mouse to evaluate a panel of anti-hOX40 mAb and show that their activities relate directly to two key properties: 1) isotype – with mIgG1 mAb evoking receptor agonism and CD8+ T cell expansion and mIgG2a mAb evoking deletion of Treg and; 2) epitope - with membrane-proximal mAb delivering more powerful agonism. Intriguingly, both isotypes acted therapeutically in tumour models by engaging these different mechanisms. These findings highlight the significant impact of isotype and epitope on the modulation of anti-hOX40 mAb therapy, and indicate that CD8+ T cell expansion or Treg depletion might be preferable according to the composition of different tumours.SummaryHuman trials with anti-OX40 antibodies have been disappointing indicating that optimal reagents have not yet been developed. Here, using a new panel of antibodies, we show that isotype and epitope combine to determine agonistic and therapeutic activity.
Shear flow-driven actin re-organization induces ICAM-1 nanoclustering on endothelial cells that impact T-cell migration
Authors: Piechocka Izabela K. , Keary Sarah , Sosa-Costa Alberto , Lau Lukas , Mohan Nitin , Stanisavljevic Jelena , Borgman Kyra J. E. , Lakadamyali Melike , Manzo Carlo , Garcia-Parajo Maria F. 
Published: June 2020

ABSTRACTThe leukocyte specific β2-integrin LFA-1, and its ligand ICAM-1 expressed on endothelial cells (ECs), are involved in the arrest, adhesion and transendothelial migration of leukocytes. Although the role of mechanical forces on LFA-1 activation is well established, the impact of forces on its major ligand ICAM-1, has received less attention. Using a parallel-plate flow chamber combined with confocal and super-resolution microscopy, we show that prolonged shear-flow induces a global translocation of ICAM-1 on ECs upstream of flow direction. Interestingly, shear-forces promoted ICAM-1 nanoclustering prior to LFA-1 engagement. This spatial nanoscale organization was driven by actin cytoskeleton re-arrangements induced by shear-force. We further assessed the impact of prolonged shear-stress EC stimulation on T cell migration. T cells adhered to mechanically pre-stimulated ECs developed a more pro-migratory phenotype, migrated faster and exhibited shorter EC interactions than when adhered to non-mechanically stimulated ECs. Together, our results indicate that shear-forces increase the number of ICAM-1/LFA-1 bonds due to ICAM-1 nanoclustering, strengthening adhesion and thereby reducing actin retrograde flow of T-cells, leading to their increased migration speed. Our data also underscores the importance of mechanical forces regulating the spatial organization of cell membrane receptors and their contribution to adhesion regulation, regardless of integrin activation.Summary statementWe show that shear forces promote ICAM-1 spatial re-arrangement and actin-dependent nanoclustering on ECs prior to integrin engagement. This mechanism might be important for firm leukocyte adhesion and migration during the immune response.
Rethinking root-shoot growth dynamics
Authors: Robinson David 
Published: June 2020

AbstractUsing a simple plant growth model based on the logistic equation I re-evaluate how biomass allocation between roots and shoots articulates dynamically with the rate of whole-plant biomass production. Defined by parameters reflecting lumped physiological properties, the model constrains roots and shoots to grow sigmoidally over time. From those temporal patterns detailed trajectories of allocation and growth rate are reconstructed. Sigmoid growth trajectories of roots and shoots are incompatible with the dominant ‘functional equilibrium’ model of adaptive allocation and growth often used to explain plants’ responses to nutrient shortage and defoliation. Anything that changes the differential rates of growth between roots and shoots will automatically change allocation and, unavoidably, change whole-plant growth rate. Biomass allocation and whole-plant growth rate are not independent traits. Allocation and growth rate have no unique relationship to one another but can vary across a wide spectrum of possible relationships. When root-shoot allocation seems to respond to the environment it is likely to be a secondary illusory consequence of other primary responses such as localised root proliferation in soil or leaf expansion within canopy gaps. Changes in root-shoot allocation cannot themselves compensate directly for an impairment of growth rate caused by an external factor such as nutrient shortage or defoliation; therefore, such changes cannot be ‘adaptive’.‘The reasons are so simple they often escape notice.’ (James 2012, p. 6).
Grooming interventions in female rhesus macaques as social niche construction
Authors: Mielke Alexander , Bruchmann Carina , Schülke Oliver , Ostner Julia 
Published: June 2020

AbstractSocial animals invest time and resources into building and adapting their social environment, which emerges not only from their own but also from the decisions of other group members. Thus, individuals have to monitor interactions between others and potentially decide when and how to interfere to prevent damage to their own investment. These interventions can be subtle, as in the case of affiliative interactions such as grooming, but they can inform us about how animals structure their world and influence other group members. Here, we used interventions into grooming bouts in 29 female rhesus macaques (Macaca mulatta) to determine who intervened into which grooming bouts, why, and what determined intervention outcomes, based on kinship, dominance rank, and affiliative relationships between groomers and (potential) interveners. Using 1132 grooming bouts and 521 interventions, we show that high dominance rank of groomers reduced the risk of intervention. Bystanders, particularly when high-ranking, intervened in grooming of their kin, close affiliates, and close-ranked competitors. Interveners gained access to their close affiliates for subsequent grooming. Affiliative relationship and rank determined intervention outcomes, with reduced aggression risk facilitating grooming involving three individuals. Thus, interventions in this species involved the monitoring of grooming interactions, decision-making based on several individual and dyadic characteristics, and potentially allowed individuals to broaden their access to grooming partners, protect their own relationships, and influence their social niche.
BREC: An R package/Shiny app for automatically identifying heterochromatin boundaries and estimating local recombination rates along chromosomes
Authors: Mansour Yasmine , Chateau Annie , Fiston-Lavier Anna-Sophie 
Published: June 2020

AbstractMotivationMeiotic recombination is a vital biological process playing an essential role in genomes structural and functional dynamics. Genomes exhibit highly various recombination profiles along chromosomes associated with several chromatin states. However, eu-heterochromatin boundaries are not available nor easily provided for non-model organisms, especially for newly sequenced ones. Hence, we miss accurate local recombination rates, necessary to address evolutionary questions.ResultsHere, we propose an automated computational tool, based on the Marey maps method, allowing to identify heterochromatin boundaries along chromosomes and estimating local recombination rates. Our method, calledBREC(heterochromatinBoundaries andRECombination rate estimates) is non-genome-specific, running even on non-model genomes as long as genetic and physical maps are available. BREC is based on pure statistics and is data-driven, implying that good input data quality remains a strong requirement. Therefore, a data pre-processing module (data quality control and cleaning) is provided. Experiments show that BREC handles different markers density and distribution issues. BREC’s heterochromatin boundaries have been validated with cytological equivalents experimentally generated on the fruit flyDrosophila melanogastergenome, for which BREC returns congruent corresponding values. Also, BREC’s recombination rates have been compared with previously reported estimates. Based on the promising results, we believe our tool has the potential to help bring data science into the service of genome biology and evolution. We introduce BREC within an R-package and a Shiny web-based user-friendly application yielding a fast, easy-to-use, and broadly accessible resource.AvailabilityBREC R-package is available at the GitHub repositoryhttps://github.com/ymansour21/BREC.