bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synapse-associated astrocyte mitochondria stabilize motor circuits to prevent excitotoxicity
Authors: Zolnoski Sonja A. , Heckman Emily L. , Doe Chris Q. , Ackerman Sarah D. 
Published: December 2021

ABSTRACTEarly stages of the devastating neurodegenerative disease amyotrophic lateral sclerosis (ALS) are characterized by motor neuron hyperexcitability. During this phase, peri-synaptic astrocytes are neuroprotective. When reactive, loss of wild-type astrocyte functions results in excitotoxicity. How astrocytes stabilize motor circuit function in early-stage ALS is poorly understood. Here, we used Drosophila motor neurons to define the role of astrocyte-motor neuron metabolic coupling in a model of ALS: astrocyte knockdown of the ALS-causing gene tbph/TARDBP. In wild-type, astrocyte mitochondria were dynamically trafficked towards active motor dendrites/synapses to meet local metabolic demand. Knockdown of tbph in astrocytes resulted in motor neuron hyperexcitability, reminiscent of early-stage ALS, which was met with a compensatory accumulation of astrocyte mitochondria near motor dendrites/synapses. Finally, we blocked mitochondria-synapse association in tbph knockdown animals and observed locomotor deficits and synapse loss. Thus, synapse-associated astrocyte mitochondria stabilize motor circuits to prevent the transition from hyperexcitability to excitotoxicity.
Mapping consistent, reproducible, and transcriptionally relevant functional connectome hubs of the human brain
Authors: Xu Zhilei , Xia Mingrui , Wang Xindi , Liao Xuhong , Zhao Tengda , He Yong 
Published: December 2021

AbstractHuman brain connectomes include sets of densely connected regions, known as connectome hubs, which play a vital role in understanding global brain communication, cognitive processing, and brain disorders. However, the consistency and reproducibility of functional connectome hubs’ anatomical localization have not been established to date and the genetic signatures underlying robust connectome hubs remain unknown. Here, we conduct the first worldwide, harmonized meta-connectomic analysis by pooling resting-state functional MRI data of 5,212 healthy young adults across 61 independent cohorts. We identify highly consistent and reproducible functional connectome hubs in heteromodal and unimodal regions both across cohorts and across individuals. These connectome hubs show heterogeneous connectivity profiles and are critical for both intra- and inter-network communications. Using post-mortem gene expression data, we show that these connectome hubs have a spatiotemporally distinctive transcriptomic pattern dominated by genes involved in the neuropeptide signaling pathway, neurodevelopmental processes, and metabolic processes. These results highlight the robustness of macroscopic connectome hubs and their potential cellular and molecular underpinnings.
Mutation, selection, and the prevalence of the C. elegans heat-sensitive mortal germline phenotype
Authors: Saber Sayran , Snyder Michael , Rajaei Moein , Baer Charles F. 
Published: December 2021

AbstractC. elegans strains with the heat-sensitive mortal germline (Mrt) phenotype become progressively sterile over the course of a few tens of generations when maintained at temperatures near the upper range of C. elegans’ tolerance. Mrt is transgenerationally-heritable, and proximately under epigenetic control. Previous studies have suggested that Mrt presents a relatively large mutational target, and that Mrt is not uncommon in natural populations of C. elegans. The Mrt phenotype is not monolithic. Some strains exhibit a strong Mrt phenotype, in which individuals invariably become sterile over a few generations, whereas other strains show a weaker (less penetrant) phenotype in which the onset of sterility is slower and more stochastic. We present results in which we (1) quantify the rate of mutation to the Mrt phenotype, and (2) quantify the frequency of Mrt in a collection of 95 wild isolates. Over the course of ~16,000 meioses, we detected one mutation to a strong Mrt phenotype, resulting in a point estimate of the mutation rate UMrt≈ 6×10−5/genome/generation. We detected no mutations to a weak Mrt phenotype. 6/95 wild isolates have a strong Mrt phenotype, and although quantification of the weak Mrt phenotype is inexact, the weak Mrt phenotype is not rare in nature. We estimate a strength of selection against mutations conferring the strong Mrt phenotype , similar to selection against mutations affecting competitive fitness. The appreciable frequency of weak Mrt variants in nature combined with the low mutation rate suggests that Mrt may be maintained by balancing selection.
Reemployment of Kupffer’s vesicle cells into axial and paraxial mesoderm via transdifferentiation
Authors: Ikeda Takafumi , Inamori Kiichi , Kawanishi Toru , Takeda Hiroyuki 
Published: December 2021

AbstractKupffer’s vesicle (KV) in the teleost embryo is a fluid-filled vesicle surrounded by a layer of epithelial cells with rotating primary cilia. KV transiently acts as the left-right organizer but degenerates after the establishment of left-right asymmetric gene expression. Previous labelling experiments indicated that descendants of KV-epithelial cells are incorporated into mesodermal tissues after KV collapses (KV-collapse) in zebrafish embryos. However, the overall picture of their differentiation potency had been unclear due to the lack of suitable genetic tools and molecular analyses. In the present study, we established a novel zebrafish transgenic line with a promoter of charon, in which all KV-epithelial cells and their descendants are specifically labelled until the larval stage. We found that KV-epithelial cells underwent epithelial-mesenchymal transition upon KV-collapse and infiltrate into adjacent mesodermal progenitors, the presomitic mesoderm and chordoneural hinge. Once incorporated, the descendants of KV-epithelial cells expressed distinct mesodermal differentiation markers and contributed to the mature populations such as the axial muscles and notochordal sheath through normal developmental process. These results indicate that fully differentiated KV-epithelial cells possess unique plasticity in that they are reemployed into mesodermal lineages through transdifferentiation after they complete their initial role in KV.
Does heat tolerance actually predict animals’ geographic thermal limits?
Authors: Camacho Agustín , Rodrigues Miguel Trefaut , Jayyusi Refat , Harun Mohamed , Geraci Marco , Vinagre Catarina , Carretero Miguel , Tejedo Miguel 
Published: December 2021

AbstractTo understand species′ climatic vulnerability, our measures of species’ thermal tolerance should predict their geographic thermal limits. Yet, this assumption is ungranted. We tested if animals′ heat tolerance restrict the warmest temperatures they can live at (Tmax), distinguishing among species differently challenged by their thermal environment. For that, we compiled 2350 measurements of species’ heat tolerance indexes and corresponding Tmax, measured at different microhabitats. We show that reptiles, a flagship for climatic vulnerability studies, are particularly unbounded by their heat tolerance. Contrarily, tolerance restricted marine fish’ geography in a non-linear fashion which contrasts with terrestrial taxa. Behavioral tolerance indexes, widely used to predict vulnerability, predicted Tmax inconsistently across Tmax indexes, or were inversely related to it. Animals’ heat tolerance restricts geographic limits more strongly for more thermally challenged species. In turn, factors uncoupling heat tolerance and Tmax (plasticity, thermoregulation, adaptation) should be more important for less thermally challenged species.Significance StatementTo identify climatic vulnerability, heat tolerance indices need to predict species′ thermal limits to geographic distribution. Yet, we show that heat tolerance predicts geographic limits quite heterogeneously, depending on taxa, the type of measure of heat tolerance and how challenged are species at their hottest known location. Particularly, reptiles, a flagship of vulnerability studies, were less bounded by tolerance than taxa regarded as more capable to evade high temperatures, due to their capacity to evaporate water, find refuge, or migrate (Ex. amphibians, arthropods, birds and mammals). Measures of species’ behavioral heat tolerance may still need to improve. Factors thought to uncouple thermal tolerance and geographic limits should be stronger for less thermally challenged species.
In vitro evolution of uracil glycosylase towards DnaKJ and GroEL binding evolves different misfolded states
Authors: Melanker Oran , Goloubinoff Pierre , Schreiber Gideon 
Published: December 2021

AbstractNatural evolution is driven by random mutations that improve fitness. In vitro evolution mimics this process, however, on a short time-scale and is driven by the given bait. Here, we used directed in vitro evolution of a random library of Uracil glycosylase (eUNG) displayed on yeast surface to select for binding to chaperones GroEL, DnaK+DnaJ+ATP (DnaKJ) or E.coli cell extract (CE). Using binding to the eUNG inhibitor Ugi as probe for native foldedess, the CE selected population was further divided to Ugi binders (+U) (native) or non-binders (-U). We found that GroEL, DnaKJ and CE-U select and enrich for mutations causing eUNG to misfold, with the three being enriched in mutations in buried and conserved positions, with a tendency to increase positive charge. Still, each selection, as well as CE+U and natural evolution of eUNG has its own trajectory. While GroEL and CE-U selected for mutants highly sensitive to protease cleavage, DnaKJ selected for partially structured misfolded species with a tendency to refold, making them less sensitive to proteases. CE+U selected for more neutral mutations than natural evolution. In a more general context, our results show that GroEL has a higher tendency to purge promiscuous misfolded protein mutants from the system, while DnaKJ binds mutants misfolding-prone species that are, upon chaperone release, more likely to natively refold. CE-U shares some of the properties of GroEL and DnaKJ selected populations, while harboring also unique properties, explained by the existence of additional chaperones in CE, such as Tig, HtpG and ClpB.
Community-wide epigenetics provides novel perspectives on the ecology and evolution of marine microbiome
Authors: Seong Hoon Je , Roux Simon , Hwang Chung Yeon , Sul Woo Jun 
Published: December 2021

AbstractDNA methylation in prokaryotes is involved in many different cellular processes including cell cycle regulation and defense against viruses. To date, most prokaryotic methylation systems have been studied in culturable microorganisms, resulting in a limited understanding of DNA methylation from a microbial ecology perspective. Here, we analyze the distribution patterns of several microbial epigenetics marks in the ocean microbiome through genome-centric metagenomics across all domains of life. We show that overall, DNA methylation can readily be detected across dominant oceanic bacterial, archaeal, and viral populations, and microbial epigenetic changes correlate with population differentiation. Furthermore, our genome-wide epigenetic analysis of Pelagibacter suggests that GANTC, a DNA methyltransferase target motif, is related to the cell cycle and is affected by environmental conditions. Yet, the presence of this motif also partitions the phylogeny of the Pelagibacter phages, possibly hinting at a competitive co-evolutionary history and multiple effects of a single methylation mark.One-Sentence SummaryDNA methylation patterns are associated with ecological changes and virus-host dynamics in the marine microbiome.
The Long Noncoding RNA FEDORA is a Cell-Type- and Sex-Specific Regulator of Depression
Authors: Issler Orna , van der Zee Yentl Y , Ramakrishnan Aarthi , Xia Sunhui , Zinsmaier Alexander K , Tan Chunfeng , Li Wei , Browne Caleb J , Walker Deena M , Salery Marine , Torres-Berrío Angélica , Futamura Rita , Duffy Julia E , Labonte Benoit , Tamminga Carol A , Dupree Jeffrey L , Dong Yan , Murrough James W , Shen Li , Nestler Eric J 
Published: December 2021

AbstractWomen suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify dramatic baseline sex differences in expression of long noncoding RNAs (lncRNAs) in human postmortem brain tissue that are profoundly lost in depression. One such lncRNA, RP11-298D21.1 (which we termed FEDORA), is enriched in oligodendrocytes and neurons and upregulated in several cortical regions of depressed females but not males. We found that virally-expressing FEDORA selectively either in neurons or in oligodendrocytes of prefrontal cortex promoted depression-like behavioral abnormalities in female mice only, changes associated with cell-type-specific regulation of synaptic properties, myelin thickness, and gene expression. We also found that blood FEDORA levels have diagnostic significance for depressed women. These findings demonstrate the important role played by lncRNAs, and FEDORA in particular, in shaping the sex-specific landscape of the brain and contributing to sex differences in depression.
Remote sensing reveals multi-decadal losses of tree cover in California driven by increasing fire disturbance and climate stress
Authors: Wang Jonathan A. , Randerson James T. , Goulden Michael L. , Knight Clarke , Battles John B. 
Published: December 2021

AbstractForests provide natural climate solutions for sequestering carbon and mitigating climate change yet are threatened by increasing temperatures and disturbance. Accurate information on vegetation dynamics is lacking in some regions with forest carbon offset programs and dense forests like California. To address this, we combined remote sensing observations with geospatial databases to develop annual maps of vegetation cover (tree, shrub, herbaceous) and disturbance type (fires, harvest, and forest die-off) in California at 30 m resolution from 1985 to 2021. California lost 3783 km2 of its tree cover area (5.5% relative to initial cover). Early gains in tree cover area were more than offset by fire-driven declines, resulting in greater shrub and herbaceous cover area. Fires and tree cover area loss occurred where temperatures were high or increasing, whereas tree cover gain occurred in cooler areas. Disturbance and warming are threatening the integrity of California’s forests and its carbon offsets program.TeaserClimate and disturbance-driven tree cover loss challenges the viability of forests as natural climate solutions in California
Label-free characterisation of amyloids and alpha-Synuclein polymorphs by exploiting their intrinsic fluorescence property
Authors: Chung Chyi Wei , Stephens Amberley D. , Ward Edward , Feng Yuqing , Davis Molly Jo , Kaminski Clemens F. , Kaminski Schierle Gabriele S. 
Published: December 2021

ABSTRACTConventional in vitro aggregation assays often involve tagging with extrinsic fluorophores which can interfere with aggregation. We propose the use of intrinsic amyloid fluorescence lifetime probed using two-photon excitation and represented by model-free phasor plots, as a label-free assay to characterise amyloid structure. Intrinsic amyloid fluorescence arises from structured packing of β-sheets in amyloids and is independent of aromatic-based fluorescence. We show that different amyloids (i.e., α-Synuclein (αS), β-Lactoglobulin and TasA) and different polymorphic populations of αS (induced by aggregation in salt-free and salt buffers mimicking the intra-/extracellular environments) can be differentiated by their unique fluorescence lifetimes. Moreover, we observe that disaggregation of pre-formed fibrils of αS and βLG leads to increased fluorescence lifetimes, distinct to those of their fibrillar counterpart. Our assay presents a medium-throughput method for rapid classification of amyloids and their polymorphs (the latter of which recent studies have shown lead to different disease pathology), and for testing small molecule inhibitory compounds.
Pro-poor and inclusive growth in West Africa
Authors: Adeosun Opeoluwa Adeniyi , Tabash Mosab I. 
Published: December 2021

PurposeThis paper focuses on three key metrics of poverty, income distribution and employment to ascertain the pro-poor and inclusive-growth position of the western African region. The roles of governance structures and their interactive effects are also accommodated to capture the peculiarity of the region.Design/methodology/approachThe paper employs fixed and dynamic models.FindingsEvidence suggests that growth is pro-poor, although virtually all governance indicators are sterile in stimulating poverty reduction. The authors observe that health and education spending coupled with trade-openness stimulate pro-poor growth potentials, whereas conflicts culminate the pervasiveness of poverty in the region. By empirically answering the question of how inclusive is economic growth through the lens of income-distribution and employment, the authors show that growth has been exclusive as per-capita-GDP growth rather dampens income shared by the poorest 20%. Also, it is observed that growth has not been inclusive as the jobless-growth argument remains valid while high inequality further exacerbates unemployment in the region. It is further shown that governance has been generally weak in propelling inclusive growth except where the institutional-component of governance stimulates inclusive growth through improvement in equality and labor employability.Originality/valueThe study jointly examines the metrics of poverty, income distribution and employment to ascertain growth pro-poorness and inclusivity which are key for the achievement of African-union (AU) agenda 2063. The study captures cross-sectional dependence among selected countries which previous studies ignored.
Believing and acting on fake news related to natural food: the influential role of brand trust and system trust
Authors: Bezbaruah Subhalakshmi , Dhir Amandeep , Talwar Shalini , Tan Teck Ming , Kaur Puneet 
Published: December 2021

PurposeFake news represents a real risk for brands, particularly for firms selling essential products, such as food items. Despite this anecdotal acknowledgement, the dynamics of the relationship between fake news and brand reputation remain under-explored. The present study addresses this gap by examining the association of consumer values (universalism and openness to change), brand trust, fake news risk and system trust in the context of natural food products.Design/methodology/approachThe study utilised a cross-sectional survey design and the mall-intercept method to collect data from 498 consumers of natural food residing in India. To test the hypotheses, which were grounded in the stimulus-organism-response (SOR) framework, the collected data were analysed using covariance-based structural equation modelling in SPSS AMOS. The conceptual model proposed universalism and openness to change as stimuli, brand trust as an internal state or organism and fake news risk – captured through the tendency of consumers to believe and act on fake news – as a response.FindingsThe findings support a positive association of universalism with brand trust and a negative association with fake news risk. In comparison, openness to change has no association with either brand trust or fake news risk. Brand trust, meanwhile, is negatively related to fake news, and this association is moderated by system trust. Furthermore, brand trust partially mediates the relationship between universalism value and fake news risk.Originality/valueNotably, the present study is one of the first attempts to understand the fake news risk associated with natural food brands by utilising the SOR framework in an emerging market setting. The study provides interesting insights for policymakers, brands and consumers.
Forecasting the schedule performance resulting from the adoption of social distancing in construction projects
Authors: Onubi Hilary Omatule , Yusof Nor'Aini , Hassan Ahmad Sanusi , Bahdad Ali Ahmed Salem 
Published: December 2021

PurposeThe coronavirus disease 2019 (COVID-19) pandemic has had major impacts on the performance of construction projects that have adopted social distancing measures. This study examines the effect of social distancing measures on project schedule performance through job reorganization on construction project sites.Design/methodology/approachResponses were obtained through a survey of 154 construction projects and analysed using the partial least square structural equation modeling (PLS-SEM) technique.FindingsThe findings established that social distancing has a negative effect on schedule performance, social distancing has a positive effect on job re-organization and job re-organization has a positive effect on schedule performance. Additionally, the results indicate that job re-organization partially mediates the relationship between social distancing and schedule performance, while social distancing moderates the relationship between job re-organization and schedule performance with low social distancing having the stronger positive effect.Originality/valueThis study contributes theoretically to a greater understanding of the impact of adopting COVID-19 safety measures such as social distancing on the schedule performance of construction projects. The study also shows how social distancing could lead to schedule performance through job reorganization.
Identifying institutional barriers when implementing new technologies in the healthcare industry
Authors: Kulkov Ignat , Tsvetkova Anastasia , Ivanova-Gongne Maria 
Published: December 2021

PurposeVirtual and augmented reality solutions in medicine are generally applied in communication, training, simulation and therapy. However, like most new digital developments, these technologies face a large number of institutional barriers that are inherent to the medical sector.Design/methodology/approachFollowing Richard Scott's view on institutions and organizations, a multiple case study is used to analyze regulatory, normative and cultural-cognitive institutional pillars in the medical industry.FindingsThe results of the study demonstrate that (1) the regulatory pillar inhibits the advancement of new technologies in the approach to treatment, regulation of patient data, educational processes for medical staff, and information and financial flows; (2) the number of barriers increases based on the solution's level of disruption and the number of variable conventional procedures; (3) trust between participants in the medical industry plays an important role in introducing new technologies; (4) new participants need to address certain pillars depending on the area of application.Originality/valueThe authors discuss top-down and bottom-up approaches for overcoming institutional barriers when implementing augmented and virtual reality solutions for companies focusing on the medical market.