bluuebunny/crossref_metadata_2025_split huggingface dataset:
Waist rotation angle as an indicator of probable human collision avoidance direction for autonomous mobile robots
Authors: Tamura Hideki , Yamauchi Tatsuto , Nakauchi Shigeki , Minami Tetsuto 
Published: May 2022

AbstractCurrently, the probability of pedestrians on the streets of smart cities encountering autonomous mobile robots (AMRs) is increasing. Previous studies have discussed collision avoidance between humans as they cross paths. Their avoidance behavior toward AMRs, however, remains unclear. To address this, we experimentally investigated the avoidance direction a human would choose against an AMR approaching head-on. This experiment included recording human locomotion under such a scenario. Further, an AMR was programmed to approach from various starting points, including directly through the participants (head-on collision). The participants were directed to evade it by moving rightward or leftward, and their paths were tracked. We found that the participants did not strongly prefer either direction, suggesting that the avoidance direction is not solely determined by the participants’ attributes, such as their adherence to the traffic rules of their region. The probability of rightward evasion when the AMR approached head-on indicated that humans use different avoidance strategies when encountering other humans and obstacles. Moreover, the participants’ motion analysis revealed that they involuntarily twisted their waists in the avoidance direction before they evaded the AMR. These results suggest that this twist is the most important predictor of the avoidance direction. These findings could be encoded into the programs of AMRs to adapt these vehicles to our locomotory responses more organically.
Single trial variability in neural activity during a working memory task: A window into multiple distinct information processing sequences
Authors: Nakuci Johan , Covey Thomas J. , Shucard Janet L. , Shucard David W. , Muldoon Sarah F. 
Published: May 2022

AbstractSuccessful encoding, maintenance, and retrieval of information stored in working memory requires persistent coordination of activity among multiple brain regions. It is generally assumed that the pattern of such coordinated activity remains consistent for a given task. Thus, to separate this task-relevant signal from noise, multiple trials of the same task are completed, and the neural response is averaged across trials to generate an event-related potential (ERP). However, from trial to trial, the neuronal activity recorded with electroencephalogram (EEG) is actually spatially and temporally diverse, conflicting with the assumption of a single pattern of activity for a given task. Here, we show that variability in neuronal activity among single time-locked trials arises from the presence of multiple forms of stimulus dependent synchronized activity (i.e., distinct ERPs). We develop a data-driven classification method based on community detection to identify three discrete spatio-temporal clusters, or subtypes, of trials with different patterns of activation that are further associated with differences in decision-making processes. These results demonstrate that differences in the patterns of neural activity during working memory tasks represent fluctuations in the engagement of distinct brain networks and cognitive processes, suggesting that the brain can choose from multiple mechanisms to perform a given task.Significance StatementWorking memory is a complex cognitive ability requiring coordinated activity among multiple brain regions to encode, maintain, and retrieve information. It is generally assumed that the pattern of coordination among brain regions remains consistent and one can average data across multiple trials of the same task. We instead show that there is significant variability in the patterns of brain activity among trials of the same task and develop a method to classify brain activity into distinct subtypes of responses, each with a different spatial and temporal pattern. The subtypes are associated with differences in decision-making processes, suggesting that the brain can use multiple mechanisms to perform a given task.
Iron homeostasis governs erythroid phenotype in Polycythemia Vera
Authors: Bennett Cavan , Jackson Victoria E , Pettikiriarachchi Anne , Hayman Thomas , Schaeper Ute , Moir-Meyer Gemma , Fielding Katherine , Ataide Ricardo , Clucas Danielle , Baldi Andrew , Garnham Alexandra L , Li-Wai-Suen Connie SN , Alexander Warren S , Bahlo Melanie , Burbury Kate , Ng Ashley P , Pasricha Sant-Rayn 
Published: May 2022

AbstractPolycythemia Vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients’ hematocrit and hemoglobin concentration, placing them at risk of life-threatening thrombotic events. Our GWAS of 440 PV cases and 403,351 controls utilising UK Biobank data found that SNPs in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed over-representation of homozygous HFE mutations in PV patients. HFE influences expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of PV mouse models, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Further, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signalling via GP130 coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease.
A pro-oxidant combination of resveratrol and copper down-regulates multiple biological hallmarks of ageing and neurodegeneration
Authors: Pal Kavita , Raghuram Gorantla V , Dsouza Jenevieve , Shinde Sushma , Jadhav Vishalkumar , Shaikh Alfina , Rane Bhagyeshri , Tandel Harshali , Kondhalkar Dipali , Chaudhary Shahid , Mittra Indraneel 
Published: May 2022

AbstractSeveral hundred billion to a trillion cells die in the body every day, and cell-free chromatin particles (cfChPs) that are released from them enter into the extracellular compartments of the body, including into the circulation. We have earlier reported that cfChPs can readily enter into healthy cells to damage their DNA, activate apoptotic pathways and induce inflammatory cytokines. We hypothesized that repeated lifelong assault on healthy cells by cfChPs is the underlying cause of ageing, and that the ageing process could be retarded by deactivating cfChPs. The latter can be effected by oxygen radicals that are generated upon admixing the nutraceuticals resveratrol (R) and copper (Cu). Using confocal microscopy and antibodies against DNA and histone we detected copious presence of extra-cellular cfChPs in brain of ageing mice, and observed that these were deactivated / eradicated following prolong oral administration of small quantities of R-Cu. Deactivation / eradication of cfChPs was associated with down-regulation of several biological hallmarks of ageing in brain cells which included reduction in: 1) telomere attrition, 2) amyloid deposition, 3) DNA damage, 4) apoptosis, 5) inflammation, 6) senescence, 7) aneuploidy and 8) mitochondrial dysfunction. At a systemic level, R- Cu treatment led to significant reduction in blood levels of glucose, cholesterol and C-reactive protein. These results suggest that cfChPs may be global instigators of ageing and neurodegeneration, and that therapeutic use of R-Cu may help to retard the process of ageing.
Neural correlates for neonicotinoid-induced impairment of olfactory long-term memory
Authors: Cabirol Amélie , Calliari Nicola , Fayolle Marie , Bariselli Sara , Schloetel Jan-Gero , Haase Albrecht 
Published: May 2022

SUMMARYReports of olfactory learning and memory deficits in honey bees exposed to neonicotinoid pesticides have been accumulating over the past decades. As agonists of the nicotinic receptors to acetylcholine, neonicotinoids target most of the projection neurons conveying olfactory information to the memory brain centres, the mushroom bodies (MBs). However, the neural mechanisms by which neonicotinoids interfere with memory formation are poorly understood. Here, we investigated the consequences of chronic exposure to the neonicotinoid imidacloprid on the number of projection neuron terminal boutons and on their plasticity in the context of long-term memory formation. Using super-resolution STED microscopy, we also measured the density of synapsin-positive units (SPUs) within boutons, as synapsin is known to be enriched in new boutons following neuronal activation. We show that imidacloprid suppresses the synaptic pruning of projection neurons naturally occurring with age and experience. The resulting excessive number of boutons in the MBs of treated bees was associated with long-term memory deficits. The subset of treated bees that showed successful memory formation had a similar number of boutons as untreated bees, suggesting that synaptic pruning might have been involved in the memorization process. As the SPU density was not affected by the imidacloprid treatment, the high bouton number in the lip of treated bees was not due to synaptogenesis. Altogether, our experiments show that, by altering synaptic pruning, imidacloprid interferes with long-term memory formation.
AptaMat: a matrix-based algorithm to compare single-stranded oligonucleotides secondary structures
Authors: Binet Thomas , Avalle Bérangère , Felipe Miraine Dávila , Maffucci Irene 
Published: May 2022

AbstractComparing single-stranded nucleic acids (ssNAs) secondary structures is fundamental when investigating their function and evolution and predicting the effect of mutations on the ssNAs structures. Many comparison metrics exist, although they are either too elaborate or not enough sensitive to distinguish close ssNAs structures.In this context, we developed AptaMat, a simple and sensitive algorithm for ssNAs secondary structures comparison based on matrices representing the ssNAs secondary structures and a metric built upon the Manhattan distance in the plane. We applied AptaMat to several examples and compared the results to those obtained by the most frequently used metrics, namely the Hamming distance and the RNAdistance, and by a recently developed image-based approach. We showed that AptaMat is able to discriminate between similar sequences, outperforming all the other here considered metrics.
Efficient and accurate prime editing strategy to correct genetic alterations in hiPSC using single EF-1alpha driven all-in-one plasmids
Authors: Weuring Wout J. , Dirkx N , Vriendt E De , Smal N , Vondervoort J van de , Slot van ’t Ruben , Koetsier M , Weckhuysen S , Koeleman Bobby PC 
Published: May 2022

ABSTRACTPrime editing (PE) is currently the most effective and versatile technology to make targeted alterations in the genome. Several improvements to the PE machinery have recently been made, and have been tested in a range of model systems, including immortalized cell lines, stem-cells and animal models. While nick RNA (ncRNA)-dependent PE systems like PE3 and PE5 are currently considered to be the most effective, they come with undesired indels or SNVs at the edit locus. Here, we aimed to improve ncRNA-independent systems PE2 and PE4max by generating novel all-in-one (pAIO) plasmids, driven by a tissue-broad EF-1alpha promoter, that is especially suitable for human iPSC models, and linked to a GFP tag for fluorescent based sorting. These novel pAIO systems effectively corrected mutations observed in patients suffering from epileptic encephalopathy, including a truncating SCN1A R612* variant in HEK293T cells and a gain-of-function KCNQ2 R201C variant in patient-derived hiPSC, with edit efficiency up to 50%. We also show that introducing additional silent PAM-removing mutations can negatively influence edit efficiency. Finally, we observed an absence of genome-wide PE off-target effects at pegRNA homology sites. Taken together, our study shows an improved efficacy and accuracy of EF-1alpha driven ncRNA-independent pAIO PE plasmids in hiPSC.
A marked enhancement of a BLOC-1 gene, pallidin, associated with somnolent mouse models deficient in histamine transmission
Authors: Seugnet Laurent , Anaclet Christelle , Perier Magali , Ghersi-Egea Jean-François , Lin Jian-Sheng 
Published: May 2022

AbstractHistamine (HA) and orexin (Ox, or hypocretin) neurons act distinctly and synergistically in wake control. A double knock out mouse genotype lacking both HA and Ox shows all sleep disorders of human narcolepsy. We identified in this mouse brain a sharp upregulation of a BLOC-1 gene, pallidin that is associated with dramatic changes in the balance of cholinergic and aminergic systems in mice and an enhanced sleep in drosophila. This study demonstrates potential sleep disorders-associated compensatory mechanisms with pallid as a novel biomarker.
Hypereosinophilia causes progressive cardiac pathologies in mice
Authors: Diny Nicola Laura , Wood Megan Kay , Won Taejoon , Talor Monica Vladut , Lukban Clarisse , Bedja Djahida , Wang Nadan , Talbot C. Conover , Lin Brian Leei , Čiháková Daniela 
Published: May 2022

AbstractHypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to WT controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca2+reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice.TeaserToo many eosinophils cause inflammation in the heart and change cardiomyocyte contraction leading to poor heart function.
Combination therapy targeting inflammasome and fibrogenesis alleviates inflammation and fibrosis in a zebrafish model of silicosis
Authors: Tyrkalska Sylwia D. , Pedoto Annamaria , Martínez-López Alicia , Candel Sergio , Ros-Lucas José A. , Mesa-del-Castillo Pablo , Mulero Victoriano 
Published: May 2022

AbstractSilicosis is a long-term lung disease caused by the inhalation of large amounts of crystalline silica dust. As there is no effective treatment available, patients are provided with supportive care, and some may be considered for lung transplantation. There is therefore an evident need for a better understanding of the disease’s biology and for identifying new therapeutic targets and therapies. In this context, our group has developed a larval zebrafish model of silicosis by injecting silica crystals into the hindbrain ventricle, a cavity into which immune cells can be recruited and that mimics the alveolar environment of the human lung. The injection of silica crystals into this cavity led to the initiation of local and systemic immune responses driven through both TLR- and inflammasome-dependent signaling pathways, followed by fibrosis, as happens in human patients. The combination of the inflammasome inhibitor VX-765 and the antifibrotic agent pirfenidone was found to be the best therapy to alleviate both inflammation and fibrosis. The zebrafish model of silicosis developed here is a unique tool that will shed light onto the molecular mechanisms involved in the progression of this devastating disease and for identifying novel drugs that improve the quality of life of silicosis patients.
Effects of microplastics mixed with natural particles onDaphnia magnapopulations
Authors: Schür Christoph , Beck Joana , Lambert Scott , Scherer Christian , Oehlmann Jörg , Wagner Martin 
Published: May 2022

AbstractThe toxicity of microplastics onDaphnia magnaas a key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposedD. magnapopulations to irregular polystyrene microplastics and diatomite as natural particle (both ≤ 63 μm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 particles mL-1) and recorded the effects on overall population size and structure, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population size and structure and induced resting egg production. The terminal population size was 28–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone, highlighting that natural particles are notper seless toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental impacts of complex particle mixtures.Environmental ImplicationsWhile microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure ofDaphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can be expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.Graphical AbstractHighlightsDaphniapopulations exposed to mixtures of microplastics and diatomiteEffects on population size, structure, and resting egg productionDiatomite as natural particle more toxic than microplasticsParticle mixtures induce negative population-level effectsParticle mixtures represent more realistic exposure scenario
FAIRsoft - A practical implementation of FAIR principles for research software
Authors: del Pico Eva Martín , Gelpi Josep Lluis , Capella-Gutiérrez Salvador 
Published: May 2022

AbstractSoftware plays a crucial and growing role in research. Unfortunately, the computational component in Life Sciences research is challenging to reproduce and verify most of the time. It could be undocumented, opaque, may even contain unknown errors that affect the outcome, or be directly unavailable, and impossible to use by others. These issues are detrimental to the overall quality of scientific research. One step to address this problem is the formulation of principles that research software in the domain should meet to ensure its quality and sustainability, resembling the FAIR (Findable, Accessible, Interoperable and Reusable) Data Principles. Within the ELIXIR infrastructure, OpenEBench aims to be an open platform providing both support for scientific benchmarking and an active observatory of software quality for the universe of Life Sciences research software. We present our initial proposal to instantiate a FAIR-like framework for assessing software quality as the first step toward the implementation of such an observatory in OpenEBench.Supplementary Material:FAIRsoft - Supplementary materials FAIRsoft.SupplementaryTables FAIRsoft.SupplementaryTables-LandscapeOther Figures:figures draftRepository:https://gitlab.bsc.es/inb/elixir/software-observatory/FAIRsoft_ETL
KIF21B binds Myosin Va for Spine Entry and regulates Actin Dynamics to control Homeostatic Synaptic Downscaling
Authors: Gromova Kira V. , Thies Edda , Dürst Céline D. , Stajano Daniele , Schweizer Michaela , Mikhaylova Marina , Gee Christine E. , Kneussel Matthias 
Published: May 2022

AbstractHomeostatic synaptic plasticity adjusts the strength of synapses to restrain neuronal activity within a physiological range. Postsynaptic GKAP controls the bidirectional synaptic scaling of AMPA receptors (AMPARs) however how chronic activity triggers postsynaptic protein remodeling to downscale synaptic transmission is barely understood. Here we report that the microtubule-dependent kinesin motor KIF21B interacts with GKAP and likewise enters dendritic spines in a myosin Va- and activity-dependent manner. We observed that under conditions of chronic activity KIF21B regulates actin dynamics in spines, triggers spine removal of GluA2-containing AMPA receptors, and mediates homeostatic synaptic downscaling of AMPA receptor-mediated mEPSC amplitudes. Our data highlight a myosin-kinesin interaction that enables the entry of the microtubule-dependent motor KIF21B into actin-rich spine compartments. A slow actin turnover rate might be beneficial for efficient protein removal from excitatory synapses, suggesting a functional role of KIF21B in a GKAP- and AMPA receptor-dependent mechanism, underlying homeostatic downscaling of neuronal firing.
A dynamical low-rank approach to solve the chemical master equation for biological reaction networks
Authors: Prugger Martina , Einkemmer Lukas , Lopez Carlos F. 
Published: May 2022

AbstractSolving the chemical master equation is an indispensable tool in understanding the behavior of biological and chemical systems. In particular, it is increasingly recognized that commonly used ODE models are not able to capture the stochastic nature of many cellular processes. Solving the chemical master equation directly, however, suffers from the curse of dimensionality. That is, both memory and computational effort scale exponentially in the number of species. In this paper we propose a dynamical low-rank approach that enables the simulation of large biological networks. The approach is guided by partitioning the network into biological relevant subsets and thus avoids the use of single species basis functions that are known to give inaccurate results for biological systems. We use the proposed method to gain insight into the nature of asynchronous vs. synchronous updating in Boolean models and successfully simulate a 41 species apoptosis model on a standard desktop workstation.
In search of the universal method: a comparative survey of bottom-up proteomics sample preparation methods
Authors: Varnavides Gina , Madern Moritz , Anrather Dorothea , Hartl Natascha , Reiter Wolfgang , Hartl Markus 
Published: May 2022

AbstractRobust, efficient and reproducible protein extraction and sample processing is a key step for bottom-up proteomics analyses. While many sample preparation protocols for mass spectrometry have been described, selecting an appropriate method remains challenging, since some protein classes may require specialized solubilization, precipitation, and digestion procedures. Here we present a comprehensive comparison of 16 most widely used sample preparation methods, covering in-solution digests, device-based methods, as well as commercially available kits. We find a remarkably good performance of the majority of the protocols with high reproducibility, little method dependencies and low levels of artifact formation. However, we revealed method-dependent differences in the recovery of specific protein features, which we summarized in a descriptive guide-matrix. Our work thereby provides a solid basis for the selection of MS sample preparation strategies for a given proteomics project.