bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Physiological Synchrony through Windowed Cross-Correlation Analysis: Statistical and Theoretical Considerations
Authors: Behrens F. , Moulder R. G. , Boker S. M. , Kret M. E. 
Published: August 2020

AbstractInterpersonal synchrony is a widely studied phenomenon. A great challenge is to statistically capture the dynamics of social interactions with fluctuating levels of synchrony and varying delays between responses of individuals. Windowed Cross-Correlation analysis accounts for both characteristics by segmenting the time series into smaller windows and shifting the segments of two interacting individuals away from each other up to a maximum lag. Despite evidence showing that these parameters affect the estimated synchrony level, there is a lack of guidelines on which parameter configurations to use. The current study aimed to close this knowledge gap by comparing the effect of different parameter configurations on two outcome criteria: (1) the ability to distinguish synchrony from pseudosynchrony by means of surrogate data analyses, and (2) the sensitivity to detect change in synchrony as measured by the difference between two within-subject conditions. Focusing on physiological synchrony, we performed these analyses on heartrate, skin conductance level, pupil size, and facial expressions data. Results revealed that a range of parameters was able to discriminate synchrony from pseudosynchrony. Window size was more influential than the maximum lag with smaller window sizes showing better discrimination. No clear patterns emerged for the second criterion. Integrating the statistical findings and theoretical considerations regarding the physiological characteristics and biological boundaries of the signals, we provide recommendations for optimizing the parameter settings to the signal of interest.
Investigation of anti-IgLON5-induced neurodegenerative changes in human neurons
Authors: Ryding Matias , Gamre Mattias , Nissen Mette S , Nilsson Anna Christine , Okarmus Justyna , Poulsen Anne Amalie E , Meyer Morten , Blaabjerg Morten 
Published: August 2020

AbstractAnti-IgLON5 disease is a progressive neurological disorder, associated with autoantibodies against a neuronal cell adhesion molecule, IgLON5. In human post-mortem brain tissue neurodegeneration and accumulation of phosphorylated-Tau is found. Whether IgLON5 antibodies induce neurodegeneration or neurodegeneration provokes an immune response remains to be elucidated. To clarify this, we exposed human stem cell derived neurons to patient anti-IgLON5 antibodies.Human neural stem cells were differentiated for 14-48 days, and exposed from day 9-14, or day 13-48 to either 1) IgG from a patient with confirmed anti-IgLON5 antibodies; 2) IgG from a healthy person or left untreated. Electrical neuronal activity was quantified using a multi electrode array. Cultures were immunostained for β-tubulin III, phosphorylated-Tau and counterstained with DAPI. Other cultures were immunostained for synaptic proteins PSD95 and synaptophysin. Lactate dehydrogenase release and nuclei morphology analyses were performed to assess cell viability.Spike rates and quantity of synaptic clusters were significantly reduced in anti-IgLON5 exposed cultures, and the proportion of cells with degenerative appearance was significantly higher for the anti-IgLON5 IgG group. Furthermore, the content of cells displaying accumulation of phosphorylated-Tau was higher for anti-IgLON5 exposed cultures. After five weeks, cultures exposed to anti-IgLON5 IgG contained significantly more dying cells.In conclusion, exposure of human neurons to pathological anti-IgLON5 antibodies cause functional impairment, synaptic and neurodegenerative changes, ultimately leading to cell death. This supports autoantibodies as a causative factor responsible for the neurodegenerative changes seen in patients with anti-IgLON5 disease and mimics pathological observations.
Distinct evolutionary trajectories in asexual populations through an interplay of their size, resource availability and mutation rates
Authors: Kumawat Bhaskar , Bhat Ramray 
Published: August 2020

AbstractAsexually reproducing populations of single cells evolve through mutation, natural selection, and genetic drift to enhance their reproductive fitness. The environment provides the contexts that allow and regulate their fitness dynamics. In this work, we used Avida - a digital evolution framework - to uncover the effect of mutation rates, maximum size of the population, and the relative abundance of resources, on evolutionary outcomes in asexually reproducing populations of digital organisms. We observed that over extended simulations, the population evolved predominantly to one of several discrete fitness classes, each with distinct sequence motifs and/or phenotypes. For a low mutation rate, the organisms acquired either of four fitness values through an enhancement in the rate of genomic replication. Evolution at a relatively higher mutation rate presented a more complex picture. While the highest fitness values at a high mutation rate were achieved through enhanced genome replication rates, a suboptimal one was achieved through organisms sharing information relevant to metabolic tasks with each other. The information sharing capacity was vital to fitness acquisition and frequency of the genotype associated with it increased with greater resource levels and maximum population size. In addition, populations optimizing their fitness through such means exhibited a greater degree of genotypic heterogeneity and metabolic activity than those that improved replication rates. Our results reveal a minimal set of conditions for the emergence of interdependence within evolving populations with significant implications for biological systems in appropriate environmental contexts.
Control of dynamic cell behaviors during angiogenesis and anastomosis by Rasip 1
Authors: Lee Minkyoung , Betz Charles , Paatero Ilkka , Schellinx Niels , Yin Jianmin , Wilson Christopher William , Ye Weilan , Affolter Markus , Belting Heinz-Georg 
Published: August 2020

AbstractOrgan morphogenesis is driven by a wealth of tightly orchestrated cellular behaviors, which ensure proper organ assembly and function. Many of these cell activities involve cell-cell interactions and remodeling of the F-actin cytoskeleton. Here, we analyze the requirement for Rasip1 (Ras-interacting protein 1), an endothelial-specific regulator of junctional dynamics, during blood vessel formation. Phenotype analysis ofrasip1mutants in zebrafish embryos reveal distinct requirements for Rasip1 during sprouting angiogenesis, vascular anastomosis and lumen formation. During angiogenic sprouting, Rasip1 is required for efficient cell pairing, which is essential for multicellular tube formation. High-resolution time-lapse analyses show that these cell pairing defects are caused by a destabilization of tricellular junctions suggesting that tri-cellular junctions may serve as a counterfort to tether sprouting endothelial cells during morphogenetic cell rearrangements. During anastomosis, Rasip1 is required to establish a stable apical membrane compartment;rasip1mutants display ectopic, reticulated junctions and the apical compartment is frequently collapsed. Loss of Ccm1 and Heg1 function leads to junctional defects similar to those seen inrasip1mutants. Analysis ofradil-bsingle andrasip1/radil-bdouble mutants reveal distinct and overlapping functions of both proteins. While Rasip1 and Radil-b have similar functions during angiogenic sprouting, the junction formation during anastomosis may primarily depend on Rasip1.
FAIR sharing of molecular visualization experiences: from pictures in the cloud to collaborative virtual reality exploration in immersive 3D environments
Authors: Martinez Xavier , Baaden Marc 
Published: August 2020

AbstractMotivated by the current Covid-19 pandemic that has spurred a substantial flow of structural data we describe how molecular visualization experiences can be used to make these datasets accessible to a broad audience. Using a variety of technology vectors related to the cloud, 3D- and virtual reality gear, we examine how to share curated visualizations of structural biology, modeling and/or bioinformatics datasets for interactive and collaborative exploration. We discuss F.A.I.R. as overarching principle for sharing such visualizations. We provide four initial example scenes related to recent Covid-19 structural data together with a ready-to-use (and share) implementation in the UnityMol software.SynopsisVisualization renders structural molecular data accessible to a broad audience. We describe an approach to share molecular visualization experiences based on FAIR principles. Our workflow is exemplified with recent Covid-19 related data.
Network Medicine Framework Shows Proximity of Polyphenol Targets and Disease Proteins is Predictive of the Therapeutic Effects of Polyphenols
Authors: do Valle Italo F. , Roweth Harvey G. , Malloy Michael W. , Moco Sofia , Barron Denis , Battinelli Elisabeth , Loscalzo Joseph , Barabási Albert-László 
Published: August 2020

AbstractPolyphenols, natural products present in plant-based foods, play a protective role against several complex diseases through their antioxidant activity and by diverse molecular mechanisms. Here we developed a network medicine framework to uncover the mechanistic roles of polyphenols on health by considering the molecular interactions between polyphenol protein targets and proteins associated with diseases. We find that the protein targets of polyphenols cluster in specific neighborhoods of the human interactome, whose network proximity to disease proteins is predictive of the molecule’s known therapeutic effects. The methodology recovers known associations, such as the effect of epigallocatechin 3-O-gallate on type 2 diabetes, and predicts that rosmarinic acid (RA) has a direct impact on platelet function, representing a novel mechanism through which it could affect cardiovascular health. We experimentally confirm that RA inhibits platelet aggregation and alpha granule secretion through inhibition of protein tyrosine phosphorylation, offering direct support for the predicted molecular mechanism. Our framework represents a starting point for mechanistic interpretation of the health effects underlying food-related compounds, allowing us to integrate into a predictive framework knowledge on food metabolism, bioavailability, and drug interaction.
Analysis of Inositol Phosphate Metabolism by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry (CE-ESI-MS)
Authors: Qiu Danye , Wilson Miranda S. , Eisenbeis Verena B. , Harmel Robert K. , Riemer Esther , Haas Thomas M. , Wittwer Christopher , Jork Nikolaus , Gu Chunfang , Shears Stephen B. , Schaaf Gabriel , Kammerer Bernd , Fiedler Dorothea , Saiardi Adolfo , Jessen Henning J. 
Published: August 2020

AbstractThe analysis ofmyo-inositol phosphates (InsPs) andmyo-inositol pyrophosphates (PP-InsPs) is a daunting challenge due to the large number of possible isomers, the absence of a chromophore, the high charge density, the low abundance, and the instability of the esters and anhydrides. Given their importance in biology, an analytical approach to follow and understand this complex signaling hub is highly desirable. Here, capillary electrophoresis (CE) coupled to electrospray ionization mass spectrometry (ESI-MS) is implemented to analyze complex mixtures of InsPs and PP-InsPs with high sensitivity. Stable isotope labeled (SIL) internal standards allow for matrix-independent quantitative assignment. The method is validated in wild-type and knockout mammalian cell lines and in model organisms. SIL-CE-ESI-MS enables for the first time the accurate monitoring of InsPs and PP-InsPs arising from compartmentalized cellular synthesis pathways, by feeding cells with either [13C6]-myo-inositol or [13C6]-D-glucose. In doing so, we uncover that there must be unknown inositol synthesis pathways in mammals, highlighting the unique potential of this method to dissect inositol phosphate metabolism and signalling.
Ericoid mycorrhizal diversity increases with soil age and progressive phosphorus limitation across a 4.1 million-year chronosequence
Authors: Leopold Devin R. , Peay Kabir G. , Vitousek Peter M. , Fukami Tadashi 
Published: August 2020

AbstractEricaceous plants rely on ericoid mycorrhizal fungi for nutrient acquisition. However, the factors that affect the composition and structure of these fungal communities remain largely unknown. Here, we use a 4.1-myr soil chronosequence in Hawaii to test the hypothesis that changes in nutrient availability with soil age determine the diversity and species composition of fungi associated with ericoid roots. We sampled roots of a native Hawaiian plant,Vaccinium calycinum, and used DNA metabarcoding to quantify changes in fungal diversity and species composition. We also used a fertilization experiment at the youngest and oldest sites to assess the importance of nutrient limitation. We found an increase in diversity and a clear pattern of species turnover across the chronosequence, driven largely by putative ericoid mycorrhizal fungi. Fertilization with nitrogen at the youngest site and phosphorus at the oldest site reduced total fungal diversity, suggesting a direct role of nutrient limitation. Our results also reveal the presence of novel fungal species associated with Hawaiian Ericaceae and suggest a greater importance of phosphorus availability for communities of ericoid mycorrhizal fungi than is generally assumed.
Three-dimensional residual channel attention networks denoise and sharpen fluorescence microscopy image volumes
Authors: Chen Jiji , Sasaki Hideki , Lai Hoyin , Su Yijun , Liu Jiamin , Wu Yicong , Zhovmer Alexander , Combs Christian A. , Rey-Suarez Ivan , Chang Hungyu , Huang Chi Chou , Li Xuesong , Guo Min , Nizambad Srineil , Upadhyaya Arpita , Lee Shih-Jong J. , Lucas Luciano A.G. , Shroff Hari 
Published: August 2020

AbstractWe demonstrate residual channel attention networks (RCAN) for restoring and enhancing volumetric time-lapse (4D) fluorescence microscopy data. First, we modify RCAN to handle image volumes, showing that our network enables denoising competitive with three other state-of-the-art neural networks. We use RCAN to restore noisy 4D super-resolution data, enabling image capture over tens of thousands of images (thousands of volumes) without apparent photobleaching. Second, using simulations we show that RCAN enables class-leading resolution enhancement, superior to other networks. Third, we exploit RCAN for denoising and resolution improvement in confocal microscopy, enabling ∼2.5-fold lateral resolution enhancement using stimulated emission depletion (STED) microscopy ground truth. Fourth, we develop methods to improve spatial resolution in structured illumination microscopy using expansion microscopy ground truth, achieving improvements of ∼1.4-fold laterally and ∼3.4-fold axially. Finally, we characterize the limits of denoising and resolution enhancement, suggesting practical benchmarks for evaluating and further enhancing network performance.
Lipoprotein particles interact with membranes and transfer their cargo without receptors
Authors: Plochberger Birgit , Sych Taras , Weber Florian , Novacek Jiri , Axmann Markus , Stangl Herbert , Sezgin Erdinc 
Published: August 2020

AbstractLipid transfer from lipoprotein particles to cells is essential for lipid homeostasis. High density lipoprotein (HDL) particles are mainly captured by cell-membrane-associated scavenger receptor class B type 1 (SR-B1) from the blood stream while low and very low density lipoprotein (LDL, VLDL) particles are mostly taken up by receptor-mediated endocytosis. However, the role of the target lipid membrane itself in the transfer process has been largely neglected so far. Here, we study how lipoprotein particles (HDL, LDL and VLDL) interact with synthetic lipid bilayers and cell-derived membranes and transfer their cargo subsequently. Employing cryo-electron microscopy, spectral imaging and fluorescence (cross) correlation spectroscopy allowed us to observe integration of all major types of lipoprotein particles into the membrane and delivery of their cargo in a receptor-independent manner. Importantly, biophysical properties of the target cell membranes change upon cargo delivery. The concept of receptor-independent interaction of lipoprotein particles with membranes helps to better understand lipoprotein particle biology and can be exploited for novel treatments of dyslipidemia diseases.
Ribonucleotide incorporation characteristics around yeast autonomously replicating sequences reveal the labor division of replicative DNA polymerases
Authors: Xu Penghao , Storici Francesca 
Published: August 2020

ABSTRACTRibonucleoside monophosphate (rNMP) incorporation in DNA is a natural and prominent phenomenon resulting in DNA structural change and genome instability. While DNA polymerases have different rNMP incorporation rates, little is known whether these enzymes incorporate rNMPs following specific sequence patterns. In this study, we analyzed a series of rNMP incorporation datasets, generated from three rNMP mapping techniques, and obtained fromSaccharomyces cerevisiaecells expressing wild-type or mutant replicative DNA polymerase and ribonuclease H2 genes. We performed computational analyses of rNMP sites around early and late firing autonomously replicating sequences (ARS’s) of the yeast genome, from which bidirectional, leading and lagging DNA synthesis starts. We find the preference of rNMP incorporation on the leading strand in wild-type DNA polymerase yeast cells. The leading/lagging-strand ratio of rNMP incorporation changes dramatically within 500 nt from ARS’s, highlighting the Pol δ - Pol ε handoff during early leading-strand synthesis. Furthermore, the pattern of rNMP incorporation is markedly distinct between the leading the lagging strand. Overall, our results show the different counts and patterns of rNMP incorporation during DNA replication from ARS, which reflects the different labor of division and rNMP incorporation pattern of Pol δ and Pol ε.
Ecological fitness cost associated with the AHAS Trp574Leu mutation in feralRaphanus sativus
Authors: Vercellino Roman B. , Hernández Fernando , Pandolfo Claudio E. , Cantamutto Miguel , Presotto Alejandro 
Published: August 2020

AbstractGene mutations endowing herbicide resistance may have negative pleiotropic effects on plant fitness. Quantifying these effects is critical for predicting the evolution of herbicide resistance and developing management strategies for herbicide-resistant weeds. This study reports the effects of the acetohydroxyacid synthase (AHAS) Trp574Leu mutation throughout the life cycle of the weed feral radish (Raphanus sativusL.). Resistant and susceptible biotypes responded differently to light and water treatments in relation to germination and emergence. Under light exposure, the resistant biotype showed higher germination and emergence, but no differences were found in seed dormancy, germination in darkness and emergence from buried seeds or pods. The resistant biotype showed delayed and reduced seedling emergence relative to the susceptible biotype under rainfed conditions, but these differences between the biotypes were not detected in irrigated soil. The biotypes showed similar relative growth rates and vegetative biomass. However, under wheat interference, resistant plants had 36–46% less total above-ground biomass, 26–47% less seeds per plant, and 36–53% less plant yield than susceptible ones, and these differences were more evident at higher plant density. This study provides a better understanding of the ecological fitness cost associated with the AHAS Trp574Leu mutation in feralR. sativus. The fitness costs could reduce the frequency of the resistant allele in areas untreated with AHAS inhibiting herbicides.
The Pharmacodynamic-Toxicodynamic Relationship of AUC and CMAX in Vancomycin Induced Kidney Injury in an Animal Model
Authors: Avedissian Sean N. , Pais Gwendolyn , Liu Jiajun , O’Donnell J. Nicholas , Lodise Thomas P. , Neely Michael , Prozialeck Walter C. , Lamar Peter C. , Becher Leighton , Scheetz Marc H. 
Published: August 2020

ABSTRACTBackgroundVancomycin induces exposure-related acute kidney injury. However, the pharmacokinetic-toxicodynamic (PK-TD) relationship remains unclear.MethodsSprague-Dawley rats received IV vancomycin doses of 300mg/kg/day and 400mg/kg/day, divided once, twice, thrice or 4xdaily (i.e., QD, BID, TID or QID) over 24-hours. Up to 8-samples were drawn during the 24-hour dosing period. Twenty-four-hour urine was collected and assayed for kidney injury molecule-1 (KIM-1). Vancomycin was quantified via LC-MS/MS. Following terminal sampling, nephrectomy and histopathologic analyses were conducted. PK analyses were conducted using Pmetrics. PK exposures (i.e. AUC0-24h, CMAX0-24h,) were calculated for each rat, and PK-TD relationships were discerned.ResultsA total of 53-rats generated PK-TD data. A 2-compartment model fit the data well (Bayesian observed vs. predicted concentrations, R2=0.96). KIM-1 values were greater in QD and BID groups (P-values: QD vs TID:<0.002, QD vs QID:<0.004, BID vs TID:<0.002, and BID vs QID:<0.004). Exposure–response relationships were observed between KIM-1 vs CMAX0–24hand AUC0-24h(R2□=□ 0.7 and 0.68). Corrected Akaike’s information criterion showed CMAX0-24has most predictive PK-TD driver for vancomycin-induced kidney injury (VIKI) (−5.28 versus −1.95).ConclusionsWhile PK-TD indices are often inter-correlated, maximal concentrations and fewer doses (for the same total daily amount) resulted in increased VIKI in our rat model.
Development and cell cycle dynamics of the root apical meristem in the fernCeratopteris richardii
Authors: Aragón-Raygoza Alejandro , Vasco Alejandra , Blilou Ikram , Herrera-Estrella Luis , Cruz-Ramírez Alfredo 
Published: August 2020

AbstractFerns are a representative clade in plant evolution although underestimated in the genomic era.Ceratopteris richardiiis an emergent model for developmental processes in ferns, yet a complete scheme of the different growth stages is necessary. Here, we present a developmental analysis, at the tissue and cellular levels, of the first shoot-borne root of Ceratopteris. We followed early stages and emergence of the root meristem in sporelings. While assessing root growth, the first shoot-borne root ceases its elongation between the emergence of the fifth and sixth roots, suggesting Ceratopteris roots follow a determinate developmental program. We report cell division frequencies in the stem cell niche after detecting labeled nuclei in the root apical cell (RAC) and derivatives after 8 hours of exposure. These results demonstrate the RAC has a continuous mitotic activity during root development. Detection of cell cycle activity in the RAC at early times suggests this cell acts as a non-quiescent organizing center. Overall, our results provide a framework to study root function and development in ferns and to better understand the evolutionary history of this organ.Summary StatementIn the Ceratopteris root, the apical cell and its derivatives have a high division frequency, suggesting the apical cell acts as a non-quiescent organizing center in the stem cell niche.