bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D-surface reconstruction of cellular cryo-soft X-ray microscopy tomograms using semi-supervised deep learning
Authors: Dyhr Michael C. A. , Sadeghi Mohsen , Moynova Ralitsa , Knappe Carolin , Kepsutlu Burcu , Werner Stephan , Schneider Gerd , McNally James , Noe Frank , Ewers Helge 
Published: May 2022

AbstractCryo-soft X-ray tomography (cryo-SXT) is a powerful method to investigate the ultrastructure of cells, offering resolution in the tens of nm range and strong contrast for membranous structures without requirement for labeling or chemical fixation. The short acquisition time and the relatively large volumes acquired allow for fast acquisition of large amounts of tomographic image data. Segmentation of these data into accessible features is a necessary step in gaining biologically relevant information from cryo-soft X-ray tomograms. However, manual image segmentation still requires several orders of magnitude more time than data acquisition. To address this challenge, we have here developed an end-to-end automated 3D-segmentation pipeline based on semi-supervised deep learning. Our approach is suitable for high-throughput analysis of large amounts of tomographic data, while being robust when faced with limited manual annotations and variations in the tomographic conditions. We validate our approach by extracting three-dimensional information on cellular ultrastructure and by quantifying nanoscopic morphological parameters of filopodia in mammalian cells.
CUGIC: The Consolidated Urban Green Infrastructure Classification for assessing ecosystem services and biodiversity
Authors: Morpurgo Joeri , Remme Roy P. , Van Bodegom Peter M. 
Published: May 2022

AbstractGreen infrastructure (GI) classifications are widely applied to predict and assess its suitability for urban biodiversity and ecosystem service (ES) provisioning. However, there is no consolidated classification, which hampers elucidating synthesis and consolidated relationships across ES and biodiversity.In this research, we aim to bridge the gap between urban GI research on ES and biodiversity by providing a standardized common classification that enables consistent spatial analysis.We analyzed GI classifications used across five ES and four taxa in scientific literature. GI classes were analyzed based on name, definition and characteristics. Results were used to create a novel classification scheme accounting for both ES and biodiversity.We show that many GI classes are unique to a ES or taxon, indicating a lack of multifunctionality of the classification applied. Among the universally used classes, diversity in their definitions is large, reducing our mechanistic understanding of multifunctionality in GI. Finally, we show that most GI classes are solely based on land-use or land-cover, lacking in-depth detail on vegetation. Through standardization and incorporation of key characteristics, we created a consolidated classification. This classification is fully available through openly-accessible databases.Our consolidated standardized classification accommodates interdisciplinary research on ES and biodiversity and allows elucidating urban biodiversity and ES relationships into greater detail, facilitating cross-comparisons and integrated assessments. This will provide a foundation for future research efforts into GI multi-functionality and urban greening policies.
Extensive lineage-specific rediploidisation masks shared whole genome duplication in the sturgeon-paddlefish ancestor
Authors: Redmond Anthony K. , Gundappa Manu Kumar , Macqueen Daniel J. , McLysaght Aoife 
Published: May 2022

AbstractWhole genome duplication (WGD) is a dramatic evolutionary event generating many new genes and which may play a role in survival through mass extinctions. Paddlefish and sturgeon are sister lineages that both show genomic evidence for ancient WGD. Until now this has been interpreted as two independent WGD events due to a preponderance of duplicate genes with independent histories. Here we show that although there is indeed a plurality of apparently ‘independent’ gene duplications, these derive from a shared genome duplication event occurring close to the Permian-Triassic mass extinction period, followed by a prolonged process of reversion to stable diploid inheritance (rediploidisation). We show that the sharing of this WGD is masked by the fact that paddlefish and sturgeon lineage divergence occurred before rediploidisation had proceeded even half-way. Thus, for most genes the resolution to diploidy was lineage-specific. Because genes are only truly duplicated once diploid inheritance is established, the paddlefish and sturgeon genomes are a mosaic of shared and non-shared gene duplications resulting from a shared genome duplication event. This is the first time that lineage-specific resolution of genes from a common WGD event has been shown to affect such a large proportion of the genome.
From cell size and first principles to structure and function of unicellular plankton communities
Authors: Andersen K.H. , Visser A.W. 
Published: May 2022

AbstractHere we review, synthesize, and analyse the size-based approach to model unicellular plankton cells and communities. We first review how cell size influences processes of the individual the cell: uptake of dissolved nutrients and dissolved organic carbon, phototrophy, phagotrophy, and metabolism. We parameterise processes primarily from first principles, using a synthesis of existing data only when needed, and show how these processes determine minimum and maximum cell size and limiting resource concentrations. The cell level processes scale directly up to the structure and function of the entire unicellular plankton ecosystem, from heterotrophic bacteria to zooplankton. The structure is described by the Sheldon size spectrum and by the emergent trophic strategies. We develop an analytical approximate solution of the biomass size spectrum and show how the trophic strategies of osmotrophy, light- and nutrient-limited phototrophy, mixotrophy, phagotrophy depend on the resource environment. We further develop expressions to quantify the functions of the plankton community: production, respiration and losses, and carbon available to production of higher trophic levels, and show how the plankton community responds to changes in temperature and grazing from higher trophic levels. We finally discuss strengths and limitations of size-based representations and models of plankton communities and which additional trait axes will improve the representation of plankton functional diversity.
Pathogenic TDP-43 Disrupts Axon Initial Segment Structure and Neuronal Excitability in a Human iPSC Model of ALS
Authors: Harley Peter , Neves Guilherme , Riccio Federica , Machado Carolina Barcellos , Cheesbrough Aimee , R’Bibo Lea , Burrone Juan , Lieberam Ivo 
Published: May 2022

AbstractDysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes to the axon initial segment (AIS), the site of action potential generation, could impact neuronal excitability in a human iPSC model of ALS. We found that early (6-week) ALS-related TDP-43G298S motor neurons showed an increase in the length of the AIS, relative to CRISPR-corrected controls. This was linked to neuronal hyperexcitability and increased spontaneous contractions of hiPSC-myofibers in compartmentalised neuromuscular co-cultures. In contrast late (10-week) TDP-43G298S motor neurons showed reduced AIS length and hypoexcitability. At a molecular level aberrant expression of the AIS master scaffolding protein Ankyrin-G, and the AIS-specific voltage-gated ion channels SCN1A (Nav1.1) and SCN8A (Nav1.6) mirrored these dynamic changes in excitability. Finally, at all stages, TDP-43G298S motor neurons showed compromised activity-dependent plasticity of the AIS, further contributing to abnormal excitability. Our results point toward the AIS as an important subcellular target driving changes to neuronal excitability in ALS.
Transcription factors that specify cell fate activate cell cycle regulator genes to determine cell numbers in ascidian larval tissues
Authors: Kobayashi Kenji , Tokuoka Miki , Sato Hiroaki , Ariyoshi Manami , Kawahara Shiori , Fujiwara Shigeki , Kishimoto Takeo , Satou Yutaka 
Published: May 2022

SummaryIn animal development, most cell types stop dividing before terminal differentiation; thus, cell cycle control is tightly linked to cell differentiation programs. Although cell cycle control in animal development has been studied extensively, such links are not well understood. In ascidian embryos, cell lineages do not vary among individuals, and rounds of the cell cycle are determined according to cell lineages. In the present study, we first showed that maternal factors promote approximately 10 rounds of cell division without zygotic gene expression. Notochord and muscle cells stop dividing after fewer than 10 rounds of cell division, and we show that a Cdk inhibitor (Cdkn1.b) is responsible. Cdkn1.b is also necessary for epidermal cells to stop dividing. In contrast, mesenchymal and endodermal cells divided more than 10 times, and Myc, which encodes a proto-oncogenic transcription factor, is responsible for maintaining cell cycle progression in these tissues. Expression of Cdkn1.b in notochord and muscle is controlled by the same developmental programs that specify the developmental fate of notochord and muscle. Likewise, expression of Myc in mesenchyme and endoderm was under control of the same developmental programs that specify the developmental fate of mesenchyme and endoderm. Because these transcription factors that regulate Cdkn1.b and Myc are essential factors for fate specification of these tissues, cell fate specification and cell cycle control are linked by those transcription factors. In other words, ectodermal, mesodermal, and endodermal tissues in ascidian embryos control the cell cycle through Cdkn1.b and Myc, which are under the control of transcription factors that specify cell fate.
Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex
Authors: Gruszczyk Jakub , Grandvuillemin Loic , Lai-Kee-Him Josephine , Paloni Matteo , Savva Christos G. , Germain Pierre , Grimaldi Marina , Boulahtouf Abdelhay , Kwong Hok-Sau , Bous Julien , Ancelin Aurelie , Bechara Cherine , Barducci Alessandro , Balaguer Patrick , Bourguet William 
Published: May 2022

SummaryLiving organisms have developed protein sensors helping them to adapt to their environment1. The aryl hydrocarbon receptor (AHR) is an emblematic member of this class of proteins, and a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites2. However, in the absence of high-resolution structural data, a molecular understanding of how AHR is activated by such diverse compounds is lacking. Here we present a 2.85 Å cryo-electron microscopy structure of the cytosolic complex comprising AHR bound to the ligand indirubin, the chaperone Hsp90 and the co-chaperone XAP2. The structure reveals a closed Hsp90 dimer with AHR threaded through its lumen. XAP2 directly interacts with Hsp90 and the AHR ligand-binding domain, thereby acting as a brace stabilizing the entire complex. Importantly, we provide the first experimental visualization of the AHR PAS-B domain bound to a ligand, revealing a unique organization of the ligand-binding pocket and the structural determinants of ligand-binding specificity and promiscuity of the receptor. By providing unprecedented structural details of the molecular initiating event leading to AHR activation, our study rationalizes prior biochemical data and provides a framework for future mechanistic studies and structure-guided drug design.
SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to downregulate MHC-I surface expression
Authors: Arshad Najla , Laurent-Rolle Maudry , Ahmed Wesam S , Hsu Jack Chun-Chieh , Mitchell Susan M , Pawlak Joanna , Sengupta Debrup , Biswas Kabir H , Cresswell Peter 
Published: May 2022

AbstractMajor histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein β2-microglobulin (β2m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8+ T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that downregulate MHC-I expression to avoid CD8+ T cell recognition. Here we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, downregulate MHC-I expression using distinct mechanisms. One, ORF3a, a viroporin, reduces global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of β2m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a novel and specific mechanism that allows immune evasion by SARS-CoV-2.Significance StatementViruses may down-regulate MHC class I expression on infected cells to avoid elimination by cytotoxic T cells. We report that the accessory proteins ORF7a and ORF3a of SARS-CoV-2 mediate this function and delineate the two distinct mechanisms involved. While ORF3a inhibits global protein trafficking to the cell surface, ORF7a acts specifically on MHC-I by competing with β2m for binding to the MHC-I heavy chain. This is the first account of molecular mimicry of β2m as a viral mechanism of MHC-I down-regulation to facilitate immune evasion.
OGG1 inhibitor TH5487 alleviates allergic airway inflammation in mice
Authors: Tanner Lloyd , Bergwik Jesper , Bhongir Ravi KV , Pan Lang , Dong Caijuan , Kalderén Christina , Helleday Thomas , Boldogh Istvan , Adner Mikael , Egesten Arne 
Published: May 2022

AbstractAllergic asthma is a complex disease characterized by dyspnea, coughing, chest tightness and airway remodeling, for which there is no cure and is symptomatically treated with inhaled β2-agonist and/or corticosteroids. Molecular mechanisms underlying its complex pathogenesis are not fully understood. However, the 8-oxoguanine DNA glycosylase-1 (OGG1), a DNA repair protein may play a central role, as OGG1 deficiency decreases both innate and allergic inflammatory responses. In this study, administration of TH5487 to mice with OVA-induced allergic airway inflammation significantly decreased goblet cell hyperplasia and mucus production. TH5487 treatment also decreased levels of activated NF-κB and expression of proinflammatory cytokines resulting in significantly lower recruitment of eosinophils and other immune cells to the lungs. Gene expression profiling of asthma and allergy-related proteins after TH5487 treatment revealed down regulation of Arg1, Mcp1 and Ccl11, and upregulation of the negative regulator of TH2, Bcl6. In addition, the OVA-induced airway hyperresponsiveness was significantly reduced by TH5487 treatment. Taken together, the data presented in this study suggest a clinically relevant utilization of TH5487 for the treatment of allergic inflammation.Graphical abstract
Disease-modifying effects of sodium selenate in a model of drug-resistant, temporal lobe epilepsy
Authors: Casillas-Espinosa Pablo M. , Anderson Alison , Harutyunyan Anna , Li Crystal , Lee Jiyoon , Braine Emma L. , Brady Rhys D. , Sun Mujun , Huang Cheng , Barlow Christopher K. , Shah Anup D. , Schittenhelm Ralf B. , Mychasiuk Richelle , Jones Nigel C. , Shultz Sandy R. , O’Brien Terence J. 
Published: May 2022

AbstractThere are no pharmacological disease-modifying treatments that can mitigate the seizures and comorbidities associated with established chronic temporal lobe epilepsy (TLE). This study evaluated the effect of sodium selenate in the post-status epilepticus (SE) rat model of chronic drug resistant TLE. Wistar rats underwent kainic acid-induced SE or sham. Ten-weeks post-SE, rats were randomly assigned to receive either sodium selenate, levetiracetam, or vehicle treatments continuously for 4 weeks. To evaluate the effects of the treatments, 1 week of continuous video-EEG was acquired before, during, and 4, 8 weeks post-treatment, followed by behavioral tests. Targeted and untargeted proteomics and metabolomics were performed on post-mortem brain tissue to identify potential pathways associated with modified disease outcomes. Telomere length was investigated as a novel surrogate marker of disease severity. Sodium selenate treatment was able to mitigate disease severity, reducing the number of spontaneous seizures (p< 0.05), cognitive dysfunction (p< 0.05 in both novel object placement and recognition tasks), and sensorimotor deficits (p< 0.01) 8 weeks post-treatment cessation. Moreover, increased protein phosphatase 2A (PP2A) expression, reduced hyperphosphorylated tau, and reversed telomere length shortening caused by SE (p< 0.05). Network medicine integration of multi-omics/ pre-clinical outcomes identified protein-metabolite modules positively correlated with the TLE phenotype. Our results provide evidence that treatment with sodium selenate results in a sustained disease modifying effect in chronically epileptic rats in the post-KA SE model of TLE, including improved comorbid learning and memory deficits.
Understanding digital entrepreneurial intentions: A capital theory perspective
Authors: Mir Ajaz Akbar , Hassan Sharfa , Khan Sher Jahan 
Published: May 2022

PurposeDigital entrepreneurship is a highly topical, sub-specialist and contemporary branch of entrepreneurship which is providing ever-increasing range of platforms for pursuing entrepreneurship-related career options. While the academic discourses in this area are increasingly growing, there is an equal level of scant attention paid to inquire how proclivity toward this career choice is developed and influenced. In the present study, this gap has been addressed by identifying major antecedents of digital entrepreneurship intentions under the aegis of capital theory.Design/methodology/approachUsing the survey data from 287 respondents, structural equation modeling was utilized to explore the association of four antecedents: digital entrepreneurial competence, innovative cognition, social media adroitness and digital entrepreneurship role models on the goal intentions. Subsequently the association between goal intention and implementation intention to start a digital venture was also examined.FindingsThe analysis confirms the significant impact of the identified antecedents on the digital entrepreneurial volition of potential entrepreneurs. Our results demonstrate that innovativeness has the greatest impact on the goal intentions to create new digital ventures followed by the presence of role models. Digital competence is also a significant contributor in enhancing the propensity to start digital ventures while being digitally adroit has the least impact on such inclination. Lastly, our study provides empirical evidence to the linkage between goal and implementation intentions.Originality/valueThis paper informs practice on entrepreneurship education especially the role of skill-based education programs to enhance the information technology–related knowledge of students and incubation support for hands-on-training on the various dimensions of digital ventures. At policy-level institutions providing entrepreneurial education can design special tasks and learning activities that are focused on acquainting students with design thinking perspectives and lean start-up approaches.
Factors that enhance the perceived quality and student satisfaction of specialized postgraduate programs: the role of identity
Authors: Park Soohyun , Kim Kilsun 
Published: May 2022

PurposeThis study identifies the factors that postgraduate service management programs (PSMPs) in Korean Universities can use to gain competitive advantage.Design/methodology/approachA mixed-method approach was adopted in serial order to verify the role of PSMP identity in the relationship between education service quality and student satisfaction established in prior research. Study 1 is a case study designed to gain a comprehensive understanding of the PSMPs in Korea using data derived through a document review of the sources collected from the official websites of PSMPs. In Study 2, focus group interviews were conducted with students and graduates of PSMPs to gain new insights that would help attain competitive advantage. Finally, a questionnaire survey was conducted in Study 3 to statistically test the relationship between PSMP identity, education service quality and student satisfaction.FindingsEducation service quality has a positive impact on PSMP identity, PSMP identity has a positive impact on student satisfaction and PSMP identity mediates the aforementioned impacts. The results established PSMP identity as a key factor in enhancing its competitiveness.Originality/valueSince PSMPs have a short history and are limited number of cases in Korea, their justification is not well-understood by the general public and companies. This problem is not limited to PSMPs but is also shared by other specialized postgraduate programs. With comprehensive data on and new insights into PSMPs, including the determinants of competitive advantage, the results provide basic evidence for follow-up research and useful information for administrative officers in charge of specialized postgraduate programs.
Estimating the effects of shrinking the criminal justice system on criminal recidivism
Authors: Loeffler Charles E. , Braga Anthony A. 
Published: May 2022

AbstractResearch SummaryWe examined the impact of Raise the Age (RTA) in Massachusetts, which increased the maximum jurisdictional age for its juvenile court in late 2013. Using statewide re‐arraignment data and a difference‐in‐differences research design comparing affected 17‐year‐olds to unaffected 18‐year‐olds, we find that RTA increased recidivism for affected 17‐year‐olds. The observed increases in recidivism were especially large for 17‐year‐olds without prior justice involvement. This result may stem from the more extensive use of pretrial supervision or the diminished deterrence of prosecution within the Massachusetts juvenile justice system.Policy ImplicationsThis study demonstrates that prosecuting older adolescents as juveniles can exacerbate rather than reduce future justice involvement. This finding highlights the ongoing risk of unanticipated and iatrogenic impacts of criminal justice interventions. It also suggests the need for caution in further expansions of RTA until evidence of anticipated programmatic benefits can be confirmed.