bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explicit and implicit depth-cue integration: evidence of systematic biases with real objects
Authors: Campagnoli Carlo , Hung Bethany , Domini Fulvio 
Published: March 2021

AbstractIn a previous series of experiments using virtual stimuli, we found evidence that 3D shape estimation agrees to a superadditivity rule of depth-cue combination. According to this rule, adding depth cues leads to greater perceived depth magnitudes and, in principle, to depth overestimation. The mechanism underlying the superadditivity effect can be fully accounted for by a normative theory of cue integration, through the adaptation of a model of cue integration termed the Intrinsic Constraint (IC) model. As for its nature, it remains unclear whether superadditivity is a byproduct of the artificial nature of virtual environments, causing explicit reasoning to infiltrate behavior and inflate the depth judgments when a scene is richer in depth cues, or the genuine output of the process of depth-cue integration. In the present study, we addressed this question by testing whether the IC model’s prediction of superadditivity generalizes beyond VR environments to real world situations. We asked participants to judge the perceived 3D shape of cardboard prisms through a matching task. To assay the potential influence of explicit control over those perceptual estimates, we also asked participants to reach and hold the same objects with their fingertips and we analyzed the in-flight grip size during the reaching. Using physical objects ensured that all visual information was fully consistent with the stimuli’s 3D structure without computer-generated artifacts. We designed a novel technique to carefully control binocular and monocular 3D cues independently from one another, allowing to add or remove depth information from the scene seamlessly. Even with real objects, participants exhibited a clear superadditivity effect in both explicit and implicit tasks. Furthermore, the magnitude of this effect was accurately predicted by the IC model. These results confirm that superadditivity is an inherent feature of depth estimation.
Prediction errors for aversive events shape long-term memory formation through a distinct neural mechanism
Authors: Kalbe Felix , Schwabe Lars 
Published: March 2021

SUMMARYPrediction errors (PEs) have been known for decades to guide associative learning, but their role in episodic memory formation has been discovered only recently. Using an encoding task in which participants learned to predict which stimuli are followed by aversive shocks, combined with univariate, multivoxel, and large-scale network analyses of fMRI data, we show that enhanced memory for events associated with negative PEs was linked to reduced hippocampal responses to PEs and increased crosstalk between the ‘salience network’ and a frontoparietal network commonly implicated in memory formation for events that are in line with prior expectation. These PE-related effects could not be explained by mere changes in physiological arousal or the prediction itself. Our results suggest that superior memory for events associated with high PEs is driven by a distinct neural mechanism that might serve to set memories of high PE events apart from those with expected outcomes.
Non-Alcoholic Fatty Liver Disease (NAFLD) in Children and Adolescents taking Atypical Antipsychotic Medications: A Protocol for Systematic Review and Meta-Analysis
Authors: Hatem Reem , Nawaz Faisal A. , Al-Sharif Ghadah A. , Almoosa Mohammad , Kattan Wid , Tzivinikos Christos , Amirali Lila , Albanna Ammar 
Published: March 2021

ABSTRACTAtypical Antipsychotic medications are commonly prescribed to children and adolescents and are associated with important adverse effects including weight gain and metabolic syndrome. Non-Alcoholic Fatty Liver Disease (NAFLD) is not only the most common pediatric liver disease, but can also be associated with serious complications including liver cirrhosis. Given that both NAFLD and Atypical Antipsychotics (AAP) are associated with metabolic syndrome, we aimed to comprehensively examine the association between AAP and NAFLD in children and adolescents. We will conduct a systematic review following the PRISMA guidelines, of English-language literature published between 1950 and 2020, exploring NAFLD in subjects younger than 18 years on AAP.
Automated long-term two-photon imaging in head-fixed walkingDrosophila
Authors: Valle Andres Flores , Honnef Rolf , Seelig Johannes D. 
Published: March 2021

ABSTRACTThe brain ofDrosophilashows dynamics at multiple timescales, from the millisecond range of fast voltage or calcium transients to functional and structural changes occurring over multiple days. To relate such dynamics to behavior requires monitoring neural circuits across these multiple timescales in behaving animals.Here, we develop a technique for automated long-term two-photon imaging in fruit flies, during wakefulness and sleep, navigating in virtual reality over up to seven days. The method is enabled by laser surgery, a microrobotic arm for controlling forceps for dissection assistance, an automated feeding robot, as well as volumetric, simultaneous multiplane imaging. The approach is validated in the fly’s head direction system.Imaging in behaving flies over multiple timescales will be useful for understanding circadian activity, learning and long-term memory, or sleep.
Why humans are stronger but not faster after isometric strength training: specific neural, not muscular, motor unit adaptations
Authors: Del Vecchio A. , Casolo A. , Dideriksen J. , Aagaard P. , Felici F. , Falla D. , Farina D. 
Published: March 2021

AbstractWhile maximal force increases following short-term isometric strength training, the rate of force development (RFD) may remain relatively unaffected. The underlying neural and muscular mechanisms during rapid contractions after strength training are largely unknown. Since strength training increases the neural drive to muscles, it may be hypothesized that there are distinct neural or muscular adaptations determining the change in RFD independently of an increase in maximal force. Therefore, we examined motor unit population data during the rapid generation of force before and after four weeks of strength training. We observed that strength training did not change the RFD because it did not influence the number of motor units recruited per second or their initial discharge rate during rapid contractions. While strength training did not change motoneuron behaviour in the force increase phase of rapid contractions, it increased the discharge rate of motoneurons (by ∼4 spikes/s) when reaching the plateau phase (∼150 ms) of the rapid contractions, determining an increase in maximal force production. Computer simulations with a motor unit model that included neural and muscular properties, closely matched the experimental observations and demonstrated that the lack of change in RFD following training is primarily mediated by an unchanged maximal recruitment speed of motoneurons. These results demonstrate that maximal force and contraction speed are determined by different adaptations in motoneuron behaviour following strength training and indicate that increases in the recruitment speed of motoneurons are required to evoke training-induced increases in RFD.
Constructing phylogenetic relationship based on the independent selection law of genome sequences
Authors: Xiaolong Li , Hong Li , Zhenhua Yang , Zefeng Zhang 
Published: March 2021

ABSTRACTExploring the composition and evolution regularity of genome sequences and constructing phylogenetic relationship by alignment-free method in genome level are high-profile topics. Our previous researches discovered the CG and TA independent selection law s existed in genome sequences by analysis on the spectral features of 8-mer subsets of 920 eukaryote and prokaryote genomes. We found that the evolution state of genomes is determined by the intensity of the two independent selections and the degree of the mutual inhibition between them. In this study, the two independent selection patterns of 22 primate and 28 insect genome sequences were analyzed further. The two complete 8-mer motif sets containing CG or TA dinucleotide and their feature of relative frequency are proposed. We found that the two 8-mer sets and their feature are related directly to sequence evolution of genomes. According to the relative frequency of two 8-mer sets, phylogenetic trees were constructed respectively for the given primate and insect genomes. Through analysis and comparison, we found that our phylogenetic trees are more consistent with the known conclusions. The two kinds of phylogenetic relationships constructed by CG 8-mer set and TA 8-mer set are similar in insect genomes, but the phylogenetic relationship constructed by CG 8-mer set reflect the evolution state of genomes in current age and phylogenetic relationship constructed by TA 8-mer set reflect the evolution state of genomes in a slight earlier period. We thought it is the result that the TA independent selection is repressed by the CG independent selection in the process of genome evolution. Our study provides a theoretical approach to construct more objective evolution relationships in genome level.
Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in aC. eleganssensory circuit
Authors: Choi Jung-Hwan , Horowitz Lauren Bayer , Ringstad Niels 
Published: March 2021

ABSTRACTAt chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in aC. eleganschemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate thatin vivothe strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.
Acriflavine, a clinically aproved drug, inhibits SARS-CoV-2 and other betacoronaviruses
Authors: Napolitano Valeria , Dabrowska Agnieszka , Schorpp Kenji , Mourão André , Barreto-Duran Emilia , Benedyk Malgorzata , Botwina Pawel , Brandner Stefanie , Bostock Mark , Chykunova Yuliya , Czarna Anna , Dubin Grzegorz , Fröhlich Tony , Hoelscher Michael , Jedrysik Malwina , Matsuda Alex , Owczarek Katarzyna , Pachota Magdalena , Plettenburg Oliver , Potempa Jan , Rothenaigner Ina , Schlauderer Florian , Szczepanski Artur , Mohn Kristin Greve-Isdahl , Blomberg Bjorn , Sattler Michael , Hadian Kamyar , Popowicz Grzegorz Maria , Pyrc Krzysztof 
Published: March 2021

SummaryThe COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identified acriflavine as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLprocatalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models,in vivoin mice andex vivoin human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.
Extracellular vesicles produced by the human commensal gut bacteriumBacteroides thetaiotaomicronaffect host immune pathways in a cell-type specific manner that are altered in inflammatory bowel disease
Authors: Gul Lejla , Modos Dezso , Fonseca Sonia , Madgwick Matthew , Thomas John P. , Sudhakar Padhmanand , Stentz Régis , Carding Simon R. , Korcsmaros Tamas 
Published: March 2021

AbstractThe gastrointestinal (GI) tract is inhabited by a complex microbial community, which contributes to its homeostasis. Disrupted microbiome can cause GI-related diseases, including inflammatory bowel disease, therefore identifying host-microbe interactions is crucial for better understanding gut health. Bacterial extracellular vesicles (BEVs), released into the gut lumen, can cross the mucus layer and access underlying immune cells. To study cross-kingdom communication between BEVs and host, we focused on the influence of BEVs, generated byBacteroides thetaiotaomicron(VPI-5482), on host immune cells. Using single-cell RNA sequencing data and host-microbe protein-protein interaction networks, we examined the potential effect of BEVs on dendritic cells, macrophages and monocytes with particular focus on the Toll-like receptor (TLR) pathway. We identified biological processes affected in each immune cell type, and also cell-type specific processes (e.g myeloid cell differentiation). The TLR pathway analysis highlighted that BEV targets differ among cells and even between the same cells in healthy versus disease (ulcerative colitis) conditions. Ourin silicofindings were validated in BEV-monocyte co-cultures demonstrating the requirement for TLR4 in BEV-elicited NF-κ B activation. This study demonstrates that both cell-type and health condition influence BEV-host communication. The results and the pipeline can facilitate BEV-based therapy development for the treatment of IBD.
Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking
Authors: Vaidžiulytė Kotryna , Macé Anne-Sophie , Battistella Aude , Beng William , Schauer Kristine , Coppey Mathieu 
Published: March 2021

AbstractMigrating cells present a variety of paths, from random to highly directional ones. While random movement can be explained by basal intrinsic activity, persistent movement requires stable polarization. Here, we quantitatively address emergence of persistent migration in RPE1 cells over long timescales. By live-cell imaging and dynamic micropatterning, we demonstrate that the Nucleus-Golgi axis aligns with direction of migration leading to efficient cell movement. We show that polarized trafficking is directed towards protrusions with a 20 min delay, and that migration becomes random after disrupting internal cell organization. Eventually, we prove that localized optogenetic Cdc42 activation orients the Nucleus-Golgi axis. Our work suggests that polarized trafficking stabilizes the protrusive activity of the cell, while protrusive activity orients this polarity axis, leading to persistent cell migration. Using a minimal physical model, we show that this feedback is sufficient to recapitulate the quantitative properties of cell migration in the timescale of hours.
Avoiding attack: How dune wasps leverage colour and motion to detect their cryptic spider predators
Authors: Rodríguez-Morales Dulce , Tapia-McClung Horacio , Robledo-Ospina Luis , Rao Dinesh 
Published: March 2021

ABSTRACTAmbush predators depend on cryptic body colouration, stillness and a suitable hunting location to optimise the probability of prey capture. Detection of cryptic predators, such as crab spiders, by flower seeking wasps may also be hindered by wind induced movement of the flowers themselves. In a beach dune habitat,Microbembex nigrifronswasps approaching flowerheads of thePalafoxia lindeniiplant need to evaluate the flowers to avoid spider attack. Wasps may detect spiders through colour and movement cues. We tracked the flight trajectories of dune wasps as they approached occupied and unoccupied flowers under two movement conditions; when the flowers were still or moving. We simulated the appearance of the spider and the flower using psychophysical visual modelling techniques and related it to the decisions made by the wasp to land or avoid the flower. Wasps could discriminate spiders only at a very close range, and this was reflected in the shape of their trajectories. Wasps were more prone to making errors in threat assessment when the flowers are moving. Our results suggest that dune wasp predation risk is augmented by abiotic conditions such as wind and compromises their early detection capabilities.
Role of Combining Anticoagulant and Antiplatelet Agents in COVID-19 Treatment: A Rapid Review
Authors: Matli Kamal , Farah Raymond , Maalouf Mario , Costanian Christy , Chamoun Nibal , Ghanem Georges 
Published: March 2021

ABSTRACTAlthough primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic, and thromboembolic events.Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review is to highlight the role of thrombosis in COVID-19 and provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 is quite scarce. Current side effects of anticoagulation therapy emphasize the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID□19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID□19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.It was not appropriate or possible to involve patients or the public in the design, or conduct, or reporting, or dissemination plans of our research
How to incentivise doctor attendance in Bangladesh: a latent class analysis of a discrete choice experiment
Authors: Angell Blake , Khan Mushtaq , Islam Mir Raihanul , Mandeville Kate , Naher Nahitun , Hutchinson Eleanor , McKee Martin , Ahmed Syed Masud , Balabanova Dina 
Published: March 2021

AbstractObjectiveTo elicit preferences of doctors over interventions to address doctor absenteeism in rural facilities in Bangladesh, a pervasive form of corruption across the country.MethodsWe conducted a discrete choice experiment with 308 doctors across four tertiary hospitals in Dhaka, Bangladesh. Four attributes of rural postings were included based on a literature review, qualitative research and a consensus-building workshop with policymakers and key health-system stakeholders: relationship with the community, security measures, attendance-based policies, and incentive payments. Respondents’ choices were analysed with mixed multinomial logistic and latent class models and were used to simulate the likely uptake of jobs under different policy packages.ResultsAll attributes significantly impacted doctor choices (p<0.01). Doctors strongly preferred jobs at rural facilities where there was a supportive relationship with the community (β=0.93), considered good attendance in education and training (0.77) or promotion decisions (0.67), with functional security (0.67) and higher incentive payments (0.5 per 10% increase of base salary). Jobs with disciplinary action for poor attendance were disliked by respondents (-.63). Latent class analysis identified three groups of doctors that differed in their uptake of jobs. Scenario modelling identified intervention packages that differentially impacted doctor behaciour and combinations that could feasibly improve doctors’ attendance.ConclusionBangladeshi doctors have strong but varied preferences over interventions to overcome absenteeism. Some were unresponsive to intervention but a substantial number appear amenable to change. Designing policy packages that consider these differences and target particular doctors could begin to generate sustainable solutions to doctor absenteeism in rural Bangladesh.
Computational modeling of C-terminal tails to predict the calcium-dependent secretion of ER resident proteins
Authors: Trychta Kathleen A. , Xie Bing , Verma Ravi Kumar , Xu Min , Shi Lei , Harvey Brandon K. 
Published: March 2021

AbstractThe lumen of the endoplasmic reticulum (ER) has resident proteins that are critical to perform the various tasks of the ER such as protein maturation and lipid metabolism. These ER resident proteins typically have a carboxy-terminal ER retention sequence (ERS). The canonical ERS is Lys-Asp-Glu-Leu (KDEL) and when an ER resident protein moves from the ER to the Golgi, KDEL receptors (KDELRs) in the Golgi recognize the ERS and return the protein to the ER lumen. Depletion of ER calcium leads to the mass departure of ER resident proteins in a process termed exodosis, which is also regulated by KDELRs. Here, by combining computational prediction with machine learning-based models and experimental validation, we identify carboxy tail sequences of ER resident proteins divergent from the canonical “KDEL” ERS. Using molecular modeling and simulations, we demonstrated that two representative non-canonical ERS can stably bind to the KDELR. Collectively, we developed a method to predict whether a carboxy-terminal sequence acts as a putative ERS that would undergo secretion in response to ER calcium depletion and interact with the KDELRs. Identification of proteins that undergo exodosis will further our understanding of changes in ER proteostasis under physiological and pathological conditions where ER calcium is depleted.
Optical Nanosensors for Real-time Feedback on Insulin Secretion by β-Cells
Authors: Ehrlich Roni , Hendler-Neumark Adi , Wulf Verena , Amir Dean , Bisker Gili 
Published: March 2021

AbstractQuantification of insulin is essential for diabetes research in general, and for the study of pancreatic β-cell function in particular. Herein, fluorescent single-walled carbon nanotubes (SWCNT) are used for the recognition and real-time quantification of insulin. Two approaches for rendering the SWCNT sensors for insulin are compared, using surface functionalization with either a natural insulin aptamer with known affinity to insulin, or a synthetic PEGylated-lipid (C16-PEG(2000Da)-Ceramide), both of which show a modulation of the emitted fluorescence in response to insulin. Although the PEGylated-lipid has no prior affinity to insulin, the response of C16-PEG(2000Da)-Ceramide-SWCNTs to insulin is more stable and reproducible compared to the insulin aptamer-SWCNTs. The C16-PEG(2000Da)-Ceramide-SWCNTs optical response is excitation-wavelength dependent, where resonant excitation leads to a larger fluorescence decrease in response to insulin. The SWCNT sensors successfully detect insulin secreted by β-cells within the complex environment of the conditioned media. The insulin is quantified by comparing the SWCNTs fluorescence response to a standard calibration curve, and the results are found to be in agreement with an enzyme-linked immunosorbent assay (ELISA). This novel analytical tool for real time quantification of insulin secreted by β-cells provides new opportunities for rapid assessment of β-cell function, with the ability to push forward many aspects of diabetes research.