bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual fates of exogenous tau seeds: lysosomal clearance vs. cytoplasmic amplification
Authors: Kolay Sourav , Vega Anthony R. , Dodd Dana A. , Perez Valerie A. , Kashmer Omar M. , White Charles L. , Diamond Marc I. 
Published: January 2022

AbstractTau assembly propagation from the extracellular to intracellular space of a cell may underlie neurodegenerative tauopathies. The first step involves tau binding to heparan sulfate proteoglycans on the cell surface, followed by macropinocytosis. Pathological tau assemblies are thought to exit the vesicular compartment as “seeds” for replication in the cytoplasm. Tau uptake is highly efficient, but only ∼1-10% of cells that take up aggregates exhibit seeding. To investigate the basis for this observation, we used fluorescently tagged full-length (FL) tau fibrils added to native U2OS cells, and “biosensor” cells expressing FL tau or repeat domain fused to mClover (Clo). FL tau-Clo bound tubulin, but seeds triggered its aggregation in multiple locations simultaneously in the cytoplasm, generally independent of visible exogenous aggregates. Most exogenous tau trafficked to the lysosome, but imaging revealed a small percentage that slowly and steadily accumulated in the cytosol. Intracellular expression of Gal3-mRuby, which binds intravesicular galactosides and forms puncta upon vesicle rupture, revealed no evidence of vesicle damage following tau exposure. In fact, most seeded cells had no evidence of lysosome rupture. However, live cell imaging indicated that cells with pre-existing Gal3-positive puncta exhibited seeding at a slightly higher rate than the general population, indicating a potential role for vesicle instability as a predisposing factor. Clearance of tau seeds occurred rapidly in both vesicular and cytosolic fractions. Bafilomycin inhibited vesicular clearance, whereas MG132 inhibited cytosolic clearance. Tau seeds that enter the cell thus have at least two fates: lysosomal clearance that degrades most tau, and entry into the cytosol, where seeds replicate, and are cleared by the proteasome.
Revealing genomic changes responsible for cannabinoid receptor loss in parrots: mechanism and functional effects
Authors: Divín Daniel , Samblas Mercedes Goméz , Veetil Nithya Kuttiyarthu , Voukali Eleni , Świderska Zuzana , Krajzingrová Tereza , Tĕšický Martin , Beneš Vladimír , Elleder Daniel , Bartoš Oldřich , Vinkler Michal 
Published: January 2022

AbstractIn vertebrates, an ancient duplication in the genes for cannabinoid receptors (CNRs) allowed the evolution of specialised endocannabinoid receptors expressed in the brain (CNR1) and the periphery (CNR2). While dominantly conserved throughout vertebrate phylogeny, our comparative genomic analysis suggests that certain taxa may have lost either the CNR1 regulator of neural processes or, more frequently, the CNR2 involved in immune regulation. Focussing on conspicuousCNR2pseudogenization in parrots (Psittaciformes), a diversified crown lineage of cognitively-advanced birds, we highlight possible functional effects of such a loss. Parrots appear to have lost theCNR2gene at at least two separate occasions due to chromosomal rearrangement. Using gene expression data from the brain and periphery of birds with experimentally-induced sterile inflammation, we compareCNRand inflammatory marker (interleukin 1 beta,IL1B) expression patterns inCNR2-deficient parrots (represented by the budgerigar,Melopsittacus undulatusand five other parrot species) withCNR2-intact passerines (represented by the zebra finch,Taeniopygia guttata). Though no significant changes inCNRexpression were observed in either parrots or passerines during inflammation of the brain or periphery, we detected a significant up-regulation ofIL1Bexpression in the brain after stimulation with lipopolysaccharide (LPS) only in parrots. As our analysis failed to show evidence for selection on alteredCNR1functionality in parrots, compared to other birds,CNR1is unlikely to be involved in compensation forCNR2loss in modulation of the neuroimmune interaction. Thus, our results provide evidence for the functional importance ofCNR2pseudogenization for regulation of neuroinflammation.
Keeping time and rhythm by replaying a sensory-motor engram
Authors: de Lafuente Victor , Jazayeri Mehrdad , Merchant Hugo , Gracía-Garibay Otto , Cadena-Valencia Jaime , Malagón Ana M. 
Published: January 2022

AbstractImagine practicing a piece of music, or a speech, solely within the mind, without any sensory input or motor output. Our ability to implement dynamic internal representations is key for successful behavior, yet how the brain achieves this is not fully understood1–4. Here we trained primates to perceive, and internally maintain, rhythms of different tempos and performed large-scale recordings of neuronal activity across multiple areas spanning the sensory-motor processing hierarchy. Results show that perceiving and maintaining rhythms engage multiple brain areas, including visual, parietal, premotor, prefrontal, and hippocampal regions. Each area displayed oscillatory activity that reflected the temporal and spatial characteristics of an internal metronome which flexibly encoded fast, medium, and slow tempos on a trial-by-trial basis. The presence of widespread metronome-related activity across the brain, in the absence of stimuli and overt actions, is consistent with the idea that time and rhythm are maintained by a mechanism that internally replays the stimuli and actions that define well-timed behavior.
Effects of diversifying the planting period of maize on herbivorous and their natural enemies
Authors: Clemente-Orta Gemma , Alvarez Hugo Alejandro , Madeira Filipe , Albajes Ramon 
Published: January 2022

AbstractKnowledge of the specific insect densities during crop development is necessary to perform appropriate measures for the control of insect pests and to minimize yield losses. In a previous study, both spatial and temporal approaches were adopted to analyse the influence of landscape structure and field variables on herbivore and predatory insects on maize. Both types of variables influenced insect abundance, but the highest effect was found with maize phenology. Given that the field planting date could modulate the influence produced by the structure of the landscape on herbivores and predatory insects, analyses of population dynamics must be performed at both the local and landscape levels. The anterior prompted us to study these aspects in the two common planting periods (early and late) in northern Spain. The present study tests the hypothesis that the period of maize planting could have a higher effect than phenology or interannual variation on the abundance of natural enemies and herbivores on maize. Our results showed that only the abundances of ‘other herbivore thrips’ and Syrphidae were significantly different between the two planting periods. Moreover, we found significant effects of planting period when we performed yearly analysis in 2015 for Coccinellidae and Chrysopidae and in 2016 and 2017 for Aeolothrips sp. Most of the taxa had abundance peaks in earlier growth stages, which are related to pollination (before or during), while only Stethorus punctillum and Syrphidae increased later in the season. Furthermore, Frankliniella occidentalis, aphids, Syrphidae and Coccinellidae registered higher abundances in fields sown in the late planting period than in the rest of the insect species. The results of the present study highlight the effects of sowing dates on insect dynamics in maize.HighlightsHerbivorous and natural enemy abundance peaks in earlier growth stages.Abundance of thrip and Syrphidae were different between the two planting periods.Abundance of Coccinellidae, Chrysopidae and Aeolothrips sp. was different when performed yearly analysis.
Duplication and overexpression of the genes encoding a beta 1,3-glucan synthase confer the intrinsic resistance to echinocandin in Mucor circinelloides
Authors: Garcia Alexis , Huh Eun Young , Lee Soo Chan 
Published: January 2022

ABSTRACTProcedures such as solid organ transplants and cancer treatments can leave many patients in an immunocompromised state resulting in an increased susceptibility to opportunistic diseases including fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients. Currently there has been a sharp increase in mucormycosis cases as a secondary infection in patients battling SARS-CoV-2 infections. Mucorales fungi are notorious for presenting resistance to most antifungal drugs. The absence of effective means to treat these infections results in mortality rates approaching 100% in cases of disseminated infection. One of the most effective antifungal drug classes currently available are echinocandins. Echinocandins seem to be efficacious in treatment of many other fungal infections. Unfortunately, susceptibility testing has found that echinocandins have no to little effect on Mucorales. In this study, we found that the model Mucorales Mucor circinelloides genome carries three copies of the genes encoding for the echinocandin β-(1,3)-D-glucan synthase (fksA, fksB, and fksC). Interestingly, we revealed that exposing M. circinelloides to micafungin significantly increased the expression of the fksA and fksB genes when compared to an untreated control. We further uncovered that the serine/threonine phosphatase calcineurin is responsible for the overexpression of fksA and fksB as deletion of calcineurin results in a decrease in expression of all three fks genes and a lower minimal inhibitory concentration (MIC) to micafungin. Taken together, this study demonstrates that the fks gene duplication and overexpression by calcineurin contribute to the intrinsic resistance to echinocandins in Mucor.IMPORTANCEThe recent emergence of mucormycosis cases in immunocompromised patients has become a more prevalent issue. The Mucorales fungi that cause these infections are known to be highly drug resistant, thus treatment options are limited and the mortalities of these types of infections remain unacceptably high. Echinocandins are one of the latest antifungal drugs developed to successfully treat fungal infections, but it remains unclear why Mucorales fungi are resistant to these treatments. In our study, we uncovered three copies of the genes (fks) encoding the drug target for echinocandins. Furthermore, we discovered that the serine-threonine phosphatase calcineurin is regulating the over-expression of these genes, which confers resistance. By inhibiting calcineurin we found that the expression of these drug targets decreases resulting in an increase in susceptibility to echinocandins both in vitro and in vivo
Low vision impairs implicit sensorimotor adaptation in response to small errors, but not large errors
Authors: Tsay Jonathan S. , Tan Steven , Chu Marlena , Ivry Richard B. , Cooper Emily A. 
Published: January 2022

AbstractSuccessful goal-directed actions require constant fine-tuning of the motor system. This fine-tuning is thought to rely on an implicit adaptation process that is driven by sensory prediction errors (i.e., where you see your hand after reaching versus where you expected it to be). Individuals with low vision experience challenges with visuomotor control, but whether they also experience challenges with implicit adaptation is unknown. To explore this question, we assessed individuals with low vision and matched controls with normal vision on a visuomotor task designed to isolate implicit adaptation. We found that low vision was associated with attenuated implicit adaptation only for small visual errors, but not large visual errors. This result not only underscores an unappreciated motor learning impairment associated with low vision, but also highlights an important constraint on how low-fidelity visual information is processed by the nervous system to enable successful implicit adaptation.New and NoteworthyWhether implicit adaptation is also impacted by visual uncertainty intrinsic to the nervous system remains unknown. To test this, we examined 20 people who live with visual uncertainty in daily life due to low vision on a visuomotor task that isolates implicit adaptation. We found that low vision attenuates adaptation in response to small errors only, paving the way for new developments in rehabilitation and assistive devices for individuals with sensory impairments.
One-step pipetting of barcoded planar microparticles into compact monolayer assembling chip for efficient readout of multiplexed immunoassay
Authors: Bae Sangwook , Lee Daewon , Na Hunjong , Jang Jisung , Kwon Sunghoon 
Published: January 2022

AbstractBarcoded planar microparticles have many qualities suitable for developing cost-efficient multiplexed immunoassays. But at the translational research level, there are a number of technical aspects yet remain to be addressed which includes robustness and efficiency of the assay readout process. Assay readout process involves automated barcode identification and signal intensity values from each planar microparticle. For this, each microparticle has to be correctly aligned for correct barcode readout while being, ideally, compactly assembled for maximum microparticle imaging efficiency. To simultaneously achieve such alignment and assembly of microparticles but in a straightforward manner, we designed a microfluidic microparticle assembling chip that only requires a single pipetting step. Our design utilizes capillary flow based guided particle assembly, which allows maximum microparticle-based immunoassay readout efficiency. With the aid of image processing algorithms, we obtained good multiplex immunoassay readout accuracy similar to conventional imaging platforms. Our approach is applicable to both soft elastomer materials (e.g. PDMS) and rigid materials (e.g. polystyrene), the latter of which is frequently used for injection molding based mass production. We anticipate our device could help developing facile and user-friendly platform technologies based on barcoded planar microparticles.
The 2009 pandemic H1N1 hemagglutinin stalk remained antigenically stable after circulating in humans for a decade
Authors: Christensen Shannon R. , Martin Emily T. , Petrie Joshua G. , Monto Arnold S. , Hensley Scott E. 
Published: January 2022

AbstractAn H1N1 influenza virus caused a pandemic in 2009 and descendants of this virus continue to circulate seasonally in humans. Upon infection with the 2009 H1N1 pandemic strain (pH1N1), many humans produced antibodies against epitopes in the hemagglutinin (HA) stalk. HA stalk-focused antibody responses were common among pH1N1-infected individuals because HA stalk epitopes were conserved between the pH1N1 strain and previously circulating H1N1 strains. Here, we completed a series of experiments to determine if the pH1N1 HA stalk has acquired substitutions since 2009 that prevent the binding of human antibodies. We identified several amino acid substitutions that have accrued in the pH1N1 HA stalk from 2009-2019. We completed enzyme-linked immunosorbent assays, absorption-based binding assays, and surface plasmon resonance experiments to determine if these substitutions affect antibody binding. Using sera collected from 230 humans (aged 21-80 years), we found that pH1N1 HA stalk substitutions that have emerged since 2009 do not affect antibody binding. Our data suggest that the HA stalk domain of pH1N1 viruses remained antigenically stable after circulating in humans for a decade.ImportanceIn 2009, a new pandemic H1N1 (pH1N1) virus began circulating in humans. Many individuals mounted hemagglutinin (HA) stalk-focused antibody responses upon infection with the 2009 pH1N1, since the HA stalk of this virus was relatively conserved with other seasonal H1N1 strains. Here, we completed a series of studies to determine if the 2009 pH1N1 strain has undergone antigenic drift in the HA stalk domain over the past decade. We found that serum antibodies from 230 humans could not antigenically distinguish the 2009 and 2019 HA stalk. These data suggest that the HA stalk of pH1N1 has remained antigenically stable, despite the presence of high levels of HA stalk antibodies within the human population.
randtip, a generalized framework to expand incomplete phylogenies using non-molecular phylogenetic information
Authors: Ramos-Gutiérrez Ignacio , Lima Herlander , Molina-Venegas Rafael 
Published: January 2022

AbstractThe increasing availability of molecular information has lifted our understanding of species evolutionary relationships to unprecedent levels. However, current estimates of the world’s biodiversity suggest that about a fifth of all extant species are yet to be described, and we still lack molecular information for many of the known species. Hence, evolutionary biologists will have to tackle phylogenetic uncertainty for a long time to come.This prospect has urged the development of software to expand phylogenies based on non-molecular phylogenetic information, and while the available tools provide some valuable features, major drawbacks persist and some of the proposed solutions are hardly generalizable to any group of organisms.Here, we present a completely generalized and flexible framework to expand incomplete molecular phylogenies. The framework is implemented in the R package ‘randtip’, a toolkit of functions that was designed to randomly bind phylogenetically uncertain taxa in backbone phylogenies through a fully customizable and automatic procedure that uses taxonomic ranks as a major source of phylogenetic information.Although randtip is capable of automatically generating fully operative phylogenies for any group of organisms using just a list of species and a backbone tree, we stress that the ‘blind’ expansion of phylogenies (using randtip or any other available software) often leads to suboptimal solutions. Thus, we discuss a variety of circumstances that may require customizing simulation parameters beyond default settings to optimally expand the trees, including a detailed step-by-step workflow.Phylogenetic uncertainty should be tackled with caution, assessing potential pitfalls and opportunities to optimize parameter space prior to launch any simulation. Used judiciously, our framework will help evolutionary biologists to efficiently expand incomplete molecular phylogenies and thereby account for phylogenetic uncertainty in quantitative analyses.
Fasting Induces a Highly Resilient Deep Quiescent State in Muscle Stem Cells via Ketone Body Signaling
Authors: Benjamin Daniel I. , Both Pieter , Benjamin Joel S. , Nutter Christopher W. , Tan Jenna H. , Kang Jengmin , Machado Leo A. , Klein Julian D. D. , de Morree Antoine , Kim Soochi , Liu Ling , Dulay Hunter , Feraboli Ludovica , Louie Sharon M , Nomura Daniel K , Rando Thomas A. 
Published: January 2022

SummaryShort-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.
Modelling the resilience of start-ups during COVID-19 pandemic
Authors: Sreenivasan Aswathy , Suresh M. , Tuesta Panduro Juan Alfredo 
Published: January 2022

PurposeResilience, the ability of start-ups to deal with anticipated instabilities and probable disruptions, is becoming an important success element during coronavirus disease 2019 (Covid-19). To survive in this pandemic situation, resilience is an important concept for start-ups. The present paper aims to “identify”, “analyse” and “categorize” the resilience factors for start-ups during the Covid-19 pandemic using total interpretive structural modelling (TISM).Design/methodology/approachThe resilience elements of start-ups during Covid-19 were identified and shortlisted during the first phase, which included literature analysis and extensive interaction with experts. TISM was used in the second phase to investigate or to determine how the factors interplayed between the resilience factors of start-ups during Covid-19. The Matrice d'impacts Croises Multiplication Appliquee a un Classment (MICMAC) method is used to rank and categorize the factors. Closed-ended questionnaire with the scheduled interview was conducted to collect the data.FindingsThe first part of the study found ten resilience elements in total. The TISM digraph was constructed in the second step to show why one resilience component led to another. The MICMAC analysis divided these factors into four groups: autonomous, linkage, dependent and independent. These groups represented resilience variables based on their driving and dependent power, which assist executives and managers in proactively addressing them while using the TISM digraph as a guide.Research limitations/implicationsDuring the Covid-19 epidemic, this study focused primarily on resilience characteristics for Indian start-ups.Practical implicationsThis study will help key stakeholders and scholars to better understand the elements that contribute to start-up's resilience.Originality/valueThe TISM method for start-up's resilience is suggested in this paper, which is a novel attempt in the field of resilience in this industry.
Quantitative visualization of physical barriers for vulnerable pedestrians based on photogrammetry
Authors: Taniguchi Koki , Kubota Satoshi , Yasumuro Yoshihiro 
Published: January 2022

Purpose
The purpose of this study is to propose a method for vulnerable pedestrians to visualize potential obstacles on sidewalks. In recent years, the number of vulnerable pedestrians has been increasing as Japanese society has aged. The number of wheelchair users is also expected to increase in the future. Currently, barrier-free maps and street-view applications can be used by wheelchair users to check possible routes and the surroundings of their destinations in advance. However, identifying physical barriers that pose a threat to vulnerable pedestrians en route is often difficult.

Design/methodology/approach
This study uses photogrammetry to create a digital twin of the three-dimensional (3D) geometry of the existing walking space by collecting photographic images taken on sidewalks. This approach allows for the creation of high-resolution digital elevation models of the entire physical sidewalk surface from which physical barriers such as local gradients and height differences can be detected by uniform image filtering. The method can be used with a Web-based data visualization tool in a geographical information system, permitting first-person views of the ground and accurate geolocation of the barriers on the map.

Findings
The findings of this study showed that capturing the road surface with a small wide-angle camera while walking is sufficient for recording subtle 3D undulations in the road surface. The method used for capturing data and the precision of the 3D restoration results are described.

Originality/value
The proposed approach demonstrates the significant benefits of creating a digital twin of walking space using photogrammetry as a cost-effective means of balancing the acquisition of 3D data that is sufficiently accurate to show the detailed geometric features needed to navigate a walking space safely. Further, the findings showed how information can be provided directly to users through two-dimensional (2D) and 3D Web-based visualizations.