bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-infection of influenza A virus enhances SARS-CoV-2 infectivity
Authors: Bai Lei , Zhao Yongliang , Dong Jiazhen , Liang Simeng , Guo Ming , Liu Xinjin , Wang Xin , Huang Zhixiang , Sun Xiaoyi , Zhang Zhen , Dong Lianghui , Liu Qianyun , Zheng Yucheng , Niu Danping , Xiang Min , Song Kun , Ye Jiajie , Zheng Wenchao , Tang Zhidong , Tang Mingliang , Zhou Yu , Shen Chao , Dai Ming , Zhou Li , Chen Yu , Yan Huan , Lan Ke , Xu Ke
Published: October 2020

The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAVin vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.
Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
Authors: Kalnin Kirill V. , Plitnik Timothy , Kishko Michael , Zhang Jinrong , Zhang Donghui , Beauvais Adrien , Anosova Natalie G. , Tibbitts Timothy , DiNapoli Joshua M. , Huang Po-Wei D. , Huleatt James , Vincent Deanne , Fries Katherine , Karve Shrirang , Goldman Rebecca , Gopani Hardip , Dias Anusha , Tran Khang , Zacharia Minnie , Gu Xiaobo , Boeglin Lianne , Chivukula Sudha , Swearingen Ron , Landolfi Victoria , Fu Tong-Ming , DeRosa Frank , Casimiro Danilo
Published: October 2020

An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority1. Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice andCynomolgusmacaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.
IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection
Authors: Chenery AL , Rosini S , Parkinson JE , Herrera JA , Lawless Craig , Chan BHK , Loke P , MacDonald AS , Kadler KE , Sutherland TE , Allen JE
Published: October 2020

IL-13 plays a key role during protective type 2 immune responses at mucosal sites, such as during infection with nematodes. However, dysregulation of IL-13 can also contribute to the pathogenesis of atopic and fibrotic diseases such as allergic asthma. Matrix remodelling is an important component of repair processes in the lung but also a hallmark of chronic conditions involving fibrosis. Hence, understanding the role of IL-13 in tissue remodelling has important clinical implications. Since IL-13 shares receptors and signalling pathways with IL-4, disentangling the relative contributions of these type 2 cytokines has been challenging. Additionally, little is known about the singular role of IL-13 following acute tissue injury. In this study, we usedNippostrongylus brasiliensisinfection as a model of acute lung tissue damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. Importantly, we found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung following infection. Through proteomic and transcriptomic profiling, we identified IL-13-dependent changes in matrix and associated regulators. We further showed that IL-13 is required for the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 was heavily involved in the induction of cellular stress responses and regulation of lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, we propose that IL-13 has tissue-protective functions during lung injury and regulates epithelial cell responses during type 2 immunity in this acute setting.
Identification of a recently dominate sublineage inSalmonella4,[5],12:i:- sequence type 34 isolated from food animals in Japan
Authors: Arai Nobuo , Sekizuka Tsuyoshi , Tamamura-Andoh Yukino , Barco Lisa , Hinenoya Atsushi , Yamasaki Shinji , Iwata Taketoshi , Watanabe-Yanai Ayako , Kuroda Makoto , Akiba Masato , Kusumoto Masahiro
Published: October 2020

SalmonellaTyphimurium and its monophasic variant (Salmonella4,[5],12:i:-) are classified into nine clades. Clade 9 is composed of ST34 strains, including theSalmonella4,[5],12:i:-European clone, which has rapidly disseminated in humans and animals worldwide since the 2000s. To reveal the microevolution of ST34/clade 9, we analyzed the whole-genome-based phylogenetic relationships of 230SalmonellaTyphimurium andSalmonella4,[5],12:i:-strains isolated between 1998 and 2017 in Japan and other countries. We identified clade 9-2, a novel sublineage derived from the conventionalSalmonella4,[5],12:i:-clade 9 that exclusively consists of Japanese isolates. Clade 9-2 was generated by mobile genetic element-mediated stepwise genome reductions caused by IS26and prophages. Furthermore, the recently identified strains developed further resistance to antimicrobials via the acquisition of resistance genes. During this microevolution,Salmonella4,[5],12:i:-clade 9-2 has dominated among recent isolates from food animals in Japan via the emergence of clonally expanding and/or multiple host-adapted subclades.
Ecological specialisation and evolutionary reticulation in extant Hyaenidae
Authors: Westbury M V , Le Duc Diana , Duchêne David A. , Krishnan Arunkumar , Prost Stefan , Rutschmann Sereina , Grau Jose H. , Dalen Love , Weyrich Alexandra , Norén Karin , Werdelin Lars , Dalerum Fredrik , Schöneberg Torsten , Hofreiter Michael
Published: October 2020

During the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four extant genera, each of which contains only a single species. These species include the bone-cracking spotted, striped, and brown hyenas, and the specialised insectivorous aardwolf. Previous genome studies have analysed the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and insectivory, defining traits of the extant species, remain elusive. To tackle these questions, we generated an aardwolf genome and analysed it together with those from the other three species. We provide new insights into the evolutionary relationships between the species, the genomic underpinnings of their scavenging and insectivorous lifestyles, and their respective genetic diversities and demographic histories. High levels of phylogenetic discordance within the family suggest gene flow between the aardwolf lineage and the ancestral brown/striped hyena lineage. Genes related to immunity and digestion in the bone-cracking hyenas and craniofacial development in the aardwolf showed the strongest signals of selection in their respective lineages, suggesting putative key adaptations to carrion or termite feeding. We also found a family-wide expansion in olfactory receptor genes suggesting that an acute sense of smell was a key early adaptation for the Hyaenidae family. Finally, we report very low levels of genetic diversity within the brown and striped hyenas despite no signs of inbreeding, which we putatively link to their similarly slow decline in Neover the last ∼2 million years. We found much higher levels of genetic diversity in both the spotted hyena and aardwolf and more stable population sizes through time. Taken together, these findings highlight how ecological specialisation can impact the evolutionary history, demographics, and adaptive genetic changes of a lineage.
Structural analysis of rice Os4BGlu18 monolignol β-glucosidase
Authors: Baiya Supaporn , Pengthaisong Salila , Cairns James R. Ketudat
Published: October 2020

Monolignol glucosides are storage forms of monolignols, which are polymerized to lignin to strengthen plant cell walls. The conversion of monolignol glucosides to monolignols is catalyzed by monolignol β-glucosidases. Rice Os4BGlu18 β-glucosidase catalyzes hydrolysis of the monolignol glucosides, coniferin, syringin, andp-coumaryl alcohol glucoside more efficiently than other natural substrates. To understand more clearly the basis for substrate specificity of a monolignol β-glucosidase, the structure of Os4BGlu18 was determined by X-ray crystallography. Crystals of Os4BGlu18 and its complex with δ-gluconolactone diffracted to 1.7 and 2.1 Å resolution, respectively. Two protein molecules were found in the asymmetric unit of theP212121space group of their isomorphous crystals. The Os4BGlu18 structure exhibited the typical (β/α)8TIM barrel of glycoside hydrolase family 1 (GH1), but the four variable loops and two disulfide bonds appeared significantly different from other known structures of GH1 β-glucosidases. Molecular docking studies of the Os4BGlu18 structure with monolignol substrate ligands placed the glycone in a similar position to the δ-gluconolactone in the complex structure and revealed the interactions between protein and ligands. Molecular docking, multiple sequence alignment, and homology modeling identified amino acid residues at the aglycone-binding site involved in substrate specificity for monolignol β-glucosides. Thus, the structural basis of substrate recognition and hydrolysis by monolignol β-glucosidases was elucidated.
Full-length transcript sequencing of human and mouse identifies widespread isoform diversity and alternative splicing in the cerebral cortex
Authors: Jeffries A.R. , Leung SK. , Castanho I. , Moore K. , Davies J.P. , Dempster E.L. , Bray N.J. , O‘Neill P. , Tseng E. , Ahmed Z. , Collier D. , Prabhakar S. , Schalkwyk L. , Gandal M.J , Hannon E. , Mill J.
Published: October 2020

Alternative splicing is a post-transcriptional regulatory mechanism producing multiple distinct mRNA molecules from a single pre-mRNA. Alternative splicing has a prominent role in the central nervous system, impacting neurodevelopment and various neuronal functions as well as being increasingly implicated in brain disorders including autism, schizophrenia and Alzheimer’s disease. Standard short-read RNA-Seq approaches only sequence fragments of the mRNA molecule, making it difficult to accurately characterize the true nature of RNA isoform diversity. In this study, we used long-read isoform sequencing (Iso-Seq) to generate full-length cDNA sequences and map transcript diversity in the human and mouse cerebral cortex. We identify widespread RNA isoform diversity amongst expressed genes in the cortex, including many novel transcripts not present in existing genome annotations. Alternative splicing events were found to make a major contribution to RNA isoform diversity in the cortex, with intron retention being a relatively common event associated with nonsense-mediated decay and reduced transcript expression. Of note, we found evidence for transcription from novel (unannotated genes) and fusion events between neighbouring genes. Although global patterns of RNA isoform diversity were found to be generally similar between human and mouse cortex, we identified some notable exceptions. We also identified striking developmental changes in transcript diversity, with differential transcript usage between human adult and fetal cerebral cortex. Finally, we found evidence for extensive isoform diversity in genes associated with autism, schizophrenia and Alzheimer’s disease. Our data confirm the importance of alternative splicing in the cerebral cortex, dramatically increasing transcriptional diversity and representing an important mechanism underpinning gene regulation in the brain. We provide this transcript level data as a resource to the scientific community.
Neural correlates of interpersonal space permeability and flexibility in autism spectrum disorder
Authors: Massaccesi Claudia , Groessing Alexander , Rosenberger Lisa A. , Hartmann Helena , Candini Michela , di Pellegrino Giuseppe , Frassinetti Francesca , Silani Giorgia
Published: October 2020

Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.
l-DOPA stimulates the dopaminergic phenotype in human retina
Authors: Radojevic Bojana , Mauro-Herrera Margarita , Bennett Lea D.
Published: October 2020

Retinal organoids derived from inducible pluripotent stem cells were used to gain insight into the role of l-DOPA during human retinal development. Dopaminergic gene expression was indicated by assessing two dopamine receptors (DRD1 andDRD2), DOPA decarboxylase (DDC), and tyrosine hydroxylase (TH) via quantitative reverse transcription-polymerase chain reaction at various developmental stages. TH transcript levels started to express around day (D) 42, reached maximal expression ∼D63 and then decreased thereafter. At D29, proliferating retinal progenitors expressedDRD1, DRD2, andDDCat various levels of mRNA throughout the day. In the presence of l-DOPA, D29 retinal organoids expressedDRD1butDRD2mRNA expression was suppressed. Additionally, l-DOPA upregulatedTHmRNA prior to dopaminergic amacrine cell (DAC) development. After the appearance of DACs, l-DOPA phase shifted expression ofDRD2and synchronized mRNA expression ofDDC, DRD2, andTH. The present results suggest unique mechanisms for DA signaling at different stages of development in the human retina.
MaveRegistry: a collaboration platform for multiplexed assays of variant effect
Authors: Kuang Da , Weile Jochen , Kishore Nishka , Rubin Alan F. , Fields Stanley , Fowler Douglas M. , Roth Frederick P.
Published: October 2020

Multiplexed assays of variant effect (MAVEs) are capable of experimentally testing all possible single nucleotide or amino acid variants in selected genomic regions, generating ‘variant effect maps’, which provide biochemical insight and functional evidence to enable more rapid and accurate clinical interpretation of human variation. Because the international community applying MAVE approaches is growing rapidly, we developed the online MaveRegistry platform to catalyze collaboration, reduce redundant efforts, allow stakeholders to nominate targets, and enable tracking and sharing of progress on ongoing MAVE projects.

Availability and implementation

https://registry.varianteffect.org

Contact

fritz.roth@utoronto.ca
Correlation and co-localization of QTL for stomatal density and canopy temperature under drought stress in Setaria
Authors: Thathapalli Prakash Parthiban , Banan Darshi , Paul Rachel E. , Feldman Maximilian J. , Xie Dan , Freyfogle Luke , Baxter Ivan , Leakey Andrew D.B.
Published: October 2020

Mechanistic modeling indicates that stomatal conductance could be reduced to improve water use efficiency (WUE) in C4crops. Genetic variation in stomatal density and canopy temperature was evaluated in the model C4genus, Setaria. Recombinant inbred lines (RIL) derived from aSetaria italicaxSetaria viridiscross were grown with ample or limiting water supply under field conditions in Illinois. An optical profilometer was used to rapidly assess stomatal patterning and canopy temperature was measured using infrared imaging. Stomatal density and canopy temperature were positively correlated but both were negatively correlated with total above-ground biomass. These trait relationships suggest a likely interaction between stomatal density and the other drivers of water use such as stomatal size and aperture. Multiple QTLs were identified for stomatal density and canopy temperature, including co-located QTLs on chromosomes 5 and 9. The direction of the additive effect of these QTLs on chromosome 5 and 9 were in accordance with the positive phenotypic relationship between these two traits. This suggests a common genetic architecture between stomatal patterning in the greenhouse and canopy transpiration in the field, while highlighting the potential of setaria as a model to understand the physiology and genetics of WUE in C4 species.

Highlight

This article reports a phenotypic and genetic relationship between two water use related traits operating at leaf level and canopy level in a C4model crop species.
Recollection is more than retrieving context or source memory: evidence from ERPs of Recognition and Source Memory combinations
Authors: Addante Richard J. , Muller Alana , Sirianni Lindsey A.
Published: October 2020

The goal of this study was to investigate a relatively unstudied memory condition for paradoxical combinations of item + source memory confidence responses, which challenged the conventional views of the memory processes supporting item and source memory judgments. We studied instances in which people provided accurate source memory judgments (conventionally ascribed as representing recollection) after having first produced low- confidence item recognition hits for the same items (conventionally thought to reflect familiarity-based processing). This paradoxical combination does not fit traditional accounts of being recollection (because it had low-confidence recognition) nor accounts of familiarity (since it had accurate source memory), and event-related potentials (ERPs) were used to adjudicate which processes support these kinds of memories. ERP results were unlike the conventional ERP effects of memory, lacking both an FN400 and the parietal old-new effect (LPC), and instead exhibited a significant negative-going ERP effect occurring later in time (800-1200ms) in central-parietal sites. Behavioral measures of response times revealed a crossover interaction: low confident recognition hits were slower during recognition but faster during source memory when compared to the opposite pattern seen for instances of high confident hits. Results provide a comprehensive characterization of the individual variability of the FN400 and LPC effects of memory, while adding the behavioral and physiological characterization of a late negative-going ERP effect for accurate source memory without recollection. Conclusions indicated that episodic context could be retrieved independently from recollection, while suggesting a role for a process of context familiarity that is independent from item-familiarity.

Highlights

Recollection is often defined as remembering the source or context of information

Prior work used ERPs to identify times when source memory did not have recollection

Current work replicated ERPs with added response times and measures of variance

Recollection was not evident in certain source memories, which had a negative ERP

Recollection is independent of context and is more than just remembering sources

Graphical Abstract
Automated Segmentation of Fractured Distal Radii by 3D Geodesic Active Contouring ofin vivoHR-pQCT Images
Authors: Ohs Nicholas , Collins Caitlyn J. , Tourolle Duncan C. , Atkins Penny R. , Schroeder Bryant , Blauth Michael , Christen Patrik , Müller Ralph
Published: October 2020

Radius fractures are among the most common fracture types; however, there is limited consensus on the standard of care. A better understanding of the fracture healing process could help to shape future treatment protocols and thus improve functional outcomes of patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows monitoring and evaluation of the radius on the micro-structural level, which is crucial to our understanding of fracture healing. However, current radius fracture studies using HR-pQCT are limited by the lack of automated contouring routines, hence only including small number of patients due to the prohibitively time-consuming task of manually contouring HR-pQCT images.

In the present study, a new method to automatically contour images of distal radius fractures based on 3D morphological geodesic active contours (3D-GAC) is presented. Contours of 60 HR-pQCT images of fractured and conservatively treated radii spanning the healing process up to one year post-fracture are compared to the current gold standard, hand-drawn 2D contours, to assess the accuracy of the algorithm. Furthermore, robustness was established by applying the algorithm to HR-pQCT images of intact radii of 73 patients and comparing the resulting morphometric indices to the gold standard patient evaluation including a threshold- and dilation-based contouring approach. Reproducibility was evaluated using repeat scans of intact radii of 19 patients.

The new 3D-GAC approach offers contours within inter-operator variability for images of fractured distal radii (mean Dice score of 0.992 ± 0.004 versus median operator Dice score of 0.993 ± 0.006). The generated contours for images of intact radii yielded morphometric indices within thein vivoreproducibility limits compared to the current gold standard. Additionally, the 3D-GAC approach shows an improved robustness against failure (n = 4) when dealing with cortical interruptions, fracture fragments, etc. compared with the automatic, default manufacturer pipeline (n = 40). Using the 3D-GAC approach assures consistent results, while reducing the need for time-consuming hand-contouring.
Alisertib exerts KRAS allele specific anticancer effects in colorectal cancer
Authors: Ren Baojun , Gao Zhuowei , Zheng Kehong , Yang Yong , Su Pengfei , Luo Qimei , Feng Jing , Luo Zhentao , Geng Yan , Ju Yongle , Huang Zonghai
Published: October 2020

Colorectal cancer (CRC) is a common cancer causing substantial mortality and morbidity worldwide. OncogeneRASmutations occur notably in ∼45% of CRCs, associated with a poor prognosis. KRAS is subject to multiple tiers of regulation, including kinase. Aurora kinases has been implicated in many types of tumor onsets and progression, making them as a promising therapeutic targets. Alisertib (ALS), selectively inhibits Aurora kinase A (AURKA) and exerts potent anticancer activitiesin vitroandin vivostudies, but the latent anticancer effect of ALS on CRC remains unclear in the context of different KRAS mutations. This study aimed to assess the effects of ALS on RAS signaling pathway in a panel of CRC lines expressing different KRAS alleles, including Caco-2 (KRAS WT), Colo-678 (KRAS G12D), SK-CO-1 (KRAS G12V), HCT116 (KRAS G13D), CCCL-18 (KRAS A146T), and HT29 (BRAF V600E). The results showed that ALS modulated the active form of KRAS in a RAS allele specific manner across the panel of CRC lines; ALS differentially regulated RAS signal via PI3K/Akt and MAPK pathways; and ALS induced apoptosis and autophagy in a RAS allele specific manner. Of note, in combination of ALS and MEK inhibitor, selumetinib, enhanced ALS regulatory effects in CRC lines in a RAS allele specific manner on apoptosis, autophagy, and cell growth. Taken together, this study suggests that ALS differentially regulates RAS signaling pathway and manipulates cell apoptosis and autophagy in RAS allele specific manner. The combinatorial approach of ALS and MEK inhibitor may represent a new therapeutic strategy for precision therapy of CRC in a RAS allele manner.
Systematic benchmarking of tools for CpG methylation detection from Nanopore sequencing
Authors: Yuen Zaka Wing-Sze , Srivastava Akanksha , Daniel Runa , McNevin Dennis , Jack Cameron , Eyras Eduardo
Published: October 2020

DNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG methylation from Nanopore sequencing using individual reads, control mixtures of methylated and unmethylated reads, and bisulfite sequencing. We found that tools have a tradeoff between false positives and false negatives and present a high dispersion with respect to the expected methylation frequency values. We described various strategies to improve the accuracy of these tools, including a new consensus approach, METEORE (https://github.com/comprna/METEORE), based on the combination of the predictions from two or more tools that shows improved accuracy over individual tools. Snakemake pipelines are also provided for reproducibility and to enable the systematic application of our analyses to other datasets.
Coordination of RNA and protein condensation by the P granule protein MEG-3
Authors: Schmidt Helen , Putnam Andrea , Rasoloson Dominique , Seydoux Geraldine
Published: October 2020

Germ granules are RNA-protein condensates in germ cells. The mechanisms that drive germ granule assembly are not fully understood. MEG-3 is an intrinsically-disordered protein required for germ (P) granule assembly in C. elegans. MEG-3 forms gel-like condensates on liquid condensates assembled by PGL proteins. MEG-3 is related to the GCNA family and contains an N-terminal disordered region (IDR) and a predicted ordered C-terminus featuring an HMG-like motif (HMGL). Using in vitro and in vivo experiments, we find the MEG-3 C-terminus is necessary and sufficient to build MEG-3/PGL co-condensates independent of RNA. The HMGL domain is required for high affinity MEG-3/PGL binding in vitro and for assembly of MEG-3/PGL co-condensates in vivo. The MEG-3 IDR binds RNA in vitro and is required but not sufficient to recruit RNA to P granules. Our findings suggest that P granule assembly depends in part on protein-protein interactions that drive condensation independent of RNA.
PRIM1 deficiency causes a distinctive primordial dwarfism syndrome
Authors: Parry David A. , Tamayo-Orrego Lukas , Carroll Paula , Marsh Joseph A. , Greene Philip , Murina Olga , Uggenti Carolina , Leitch Andrea ,   The Scottish Genomes Partnership, Káposzta Rita , Merő Gabriella , Nagy Andrea , Orlik Brigitta , Kovács-Pászthy Balázs , Quigley Alan J. , Riszter Magdolna , Rankin Julia , Reijns Martin A.M. , Szakszon Katalin , Jackson Andrew P.
Published: October 2020

DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase as a novel disease gene. Using a variant classification agnostic approach, biallelic mutations in PRIM1 were identified in five individuals. PRIM1 protein levels were markedly reduced in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replication stress, and prolonged S-phase duration. Consequently, cell proliferation was markedly impaired, explaining the patients’ extreme growth failure. Notably, phenotypic features distinct from those previously reported with DNA polymerase genes were evident, highlighting differing developmental requirements for this core replisome component that warrant future investigation.
p53 directly represses human LINE1 transposons
Authors: Tiwari Bhavana , Jones Amanda E. , Caillet Candace J. , Das Simanti , Royer Stephanie K. , Abrams John M.
Published: October 2020

p53 is a potent tumor suppressor and commonly mutated in human cancers. Recently, we demonstrated that p53 genes act to restrict retrotransposons in germline tissues of flies and fish but whether this activity is conserved in somatic human cells is not known. Here we show that p53 constitutively restrains human LINE1s by cooperatively engaging sites in the 5′UTR and stimulating local deposition of repressive histone marks at these transposons. Consistent with this, the elimination of p53 or the removal of corresponding binding sites in LINE1s, prompted these retroelements to become hyperactive. Concurrently, p53 loss instigated chromosomal rearrangements linked to LINE sequences and also provoked inflammatory programs that were dependent on reverse transcriptase produced from LINE1s. Taken together, our observations establish that p53 continuously operates at the LINE1 promoter to restrict autonomous copies of these mobile elements in human cells. Our results further suggest that constitutive restriction of these retroelements may help to explain tumor suppression encoded by p53, since erupting LINE1s produced acute oncogenic threats when p53 was absent.
Repeated encoding fosters retention of perceptual detail in visual recognition memory
Authors: Zhang Mengting , Hupbach Almut
Published: October 2020

In a 2014 issue of Learning & Memory, Reagh and Yassa proposed that repeated encoding leads to semanticization and loss of perceptual detail in memory. We presented object images one or three times and tested recognition of targets and corresponding similar lures. Correct lure rejections after one in comparison to three exposures were more frequently associated with corresponding target misses, suggesting that higher lure rejections after one exposure reflect memory failure rather than perceptual fidelity. Signal detection theory analysis showed that three exposures improved lure-old discriminations. Thus, repeated encoding fosters rather than hinders retention of perceptual detail in visual recognition memory.
Talking money at home: the value of family financial socialization
Authors: Zhao Haidong , Zhang Lini
Published: October 2020

Purpose

The objective of this study was to empirically examine how family financial socialization affects individuals' financial outcomes, including financial literacy, financial behavior and financial well-being, based on the family financial socialization theory (FFST).

Design/methodology/approach

Using a national representative sample of 6,311 US respondents from the 2016 National Financial Well-Being Survey, structural equation modeling (SEM) was conducted to test the hypotheses in this study. Sampling weights were incorporated into the structural model using the maximum likelihood estimation with robust standard errors and a Satorra-Bentler scaled test statistic (MLM estimation).

Findings

This study concludes the effectiveness of family financial socialization by showing that parental financial socialization has significant positive impacts on financial literacy, financial behavior and financial well-being. In addition, parents' education can significantly influence the quality of parental financial socialization.

Practical implications

The result underscores the importance of financial socialization in the family context and encourages parents to discuss financial matters with their children at home. Detailed implications have been provided to financial educators, practitioners and policymakers to incorporate parental involvement in the design of financial education programs, as well as financial services providers to improve marketing strategies for their banking services.

Originality/value

This research is amongst the first to empirically explore the relationships among parental financial socialization, financial literacy, financial behavior and financial well-being based on the FFST. The study also contributes to the literature by confirming the effects of parental socialization received in childhood on adults' later financial outcomes.
Determinants of school choice and their relation to success to the institution: a comparative study between public and private schools in Bangladesh
Authors: Chowdhury Tamgid Ahmed , Synthia Ishrat Jahan
Published: October 2020

Purpose

This paper aims to identify the determinants of school choice and factors that define the success of a school as perceived by the parents and then compare “Public” and “Private” schools with respect to the explored criteria to determine the strengths and weaknesses of the institutions.

Design/methodology/approach

The study is based on 1,121 quantitative data collected through survey questionnaire from the parents living in urban areas of Bangladesh. The school choice model was developed and validated by applying structural equation modeling.

Findings

This paper offers a statistically significant, robust and reliable five-dimensional 23-item school choice model that includes both school characteristics and preferred outcomes as perceived by the parents. Characteristic-wise comparisons in terms of characteristics revealed that public schools are superior to private institutions in fulfilling several choice criteria such as parents–teacher relationships, performance of the teachers, offerings of special programs, safety assurance in the campus and in having bigger campus with playground. On the other hand, private schools dominate in providing better educational environment, arranging training to the teachers, ensuring satisfactory library services and delivering information effectively to the parents. Among outcome determinants, government schools are well ahead in creating self-discipline, morality and good work habits among students. Private schools are superior in developing critical thinking skill of the kids.

Originality/value

There is a gap of comprehensive empirical study on school choice in South Asia region that includes both school characteristics and outcomes. Therefore, this paper contributes significantly to the relevant literature.
Evaluating the effect of critical failure factors associated with sustainable Lean Six Sigma framework implementation in healthcare organization
Authors: Swarnakar Vikas , Singh A.R. , Tiwari Anil Kr
Published: October 2020

Purpose

The purpose of this study is to develop a structured hierarchical interrelationship-based model to evaluate the critical failure factors (CFFs) that affect the sustainable Lean Six Sigma (SLSS) framework implementation in a healthcare organization. Further, solution approaches have been provided that guide to eliminate them.

Design/methodology/approach

The CFFs has been identified through empirical study and clustered into six major categories for their better understanding. The interrelation among CFFs has been developed through total interpretive structural modeling (TISM) and classifies the nature using MICMAC technique. Further, prioritized the CFFs based on its driving and dependents power. The methodology enabled the decision-makers, practitioners to systematically analyze the CFFs and develop a structural model for implementing SLSS in the healthcare environment.

Findings

A total of 14 leading CFFs have been identified, and 7-level structured interrelationship-based model has been formed. The experts have provided the solution approach after careful analysis of the developed model. Based on the analysis, it was observed that the significant CFFs affect the deployment of the SLSS framework in healthcare organizations.

Research limitations/implications

The structured model and methodological approach have been tested in a healthcare organization. In the future, the approach can be applied in the different service sectors.

Practical implications

The present study has been conducted in a real-time industrial problem. The practitioners, decision-makers and academicians expressed the usefulness of methodology for understanding the CFFs interrelation and their effect on SLSS implementation. This study also guides decision-makers to systematically tackle related problems.

Originality/value

The development of a structured CFFs based model for SLSS framework implementation using the integrated TISM-MICMAC with a detailed solution approach is a unique effort in a healthcare environment.
A new method in designing group chain acceptance sampling plans (GChSP) for generalized exponential distribution
Authors: Pawan Teh Mohd Azri , Aziz Nazrina , Zain Zakiyah
Published: October 2020

Purpose

This paper introduces group chain acceptance sampling plans (GChSP) for a truncated life test at preassumed time by using the minimum angle method. The proposed method is an approach, where both risks associated with acceptance sampling, namely consumers’ and producer’s risks, are considered. Currently, the GChSP only considers the consumer's risk (CR), which means the current plan only protects the consumer not the producer since it does not take into account the producer's risk (PR) at all.

Design/methodology/approach

There are six phases involved when designing the GChSP, which are (1) identifying the design parameters, (2) implementing the operating procedures, (3) deriving the probability of lot acceptance, (4) deriving the probability of zero or one defective, (5) deriving the proportion defective and (6) measuring the performance.

Findings

The findings show that the optimal number of groups obtained satisfies both parties, i.e. consumer and producer, compared to the established GChSP, where the number of group calculated only satisfies the consumer not the producer.

Research limitations/implications

There are three limitations identified for this paper. The first limitation is the distribution, in which this paper only proposes the GChSP for generalized exponential distribution. It can be extended to different distribution available in the literature. The second limitation is that the paper uses binomial distribution when deriving the probability of lot acceptance. Also, it can be derived by using different distributions such as weighted binomial distribution, Poisson distribution and weighted Poisson distribution. The final limitation is that the paper adopts the mean as a quality parameter. For the quality parameter, researchers have other options such as the median and the percentile.

Practical implications

The proposed GChSP should provide an alternative for the industrial practitioners and for the inspection activity, as they have more options of the sampling plans before they finally decide to select one.

Originality/value

This is the first paper to propose the minimum angle method for the GChSP, where both risks, CR and PR, are considered. The GChSP has been developed since 2015, but all the researchers only considered the CR in their papers.
Next-generation prediction metrics for composite-based PLS-SEM
Authors: Hair Jr Joe F.
Published: October 2020

Purpose

The purpose of this study is to provide an overview of emerging prediction assessment tools for composite-based PLS-SEM, particularly proposed out-of-sample prediction methodologies.

Design/methodology/approach

A review of recently developed out-of-sample prediction assessment tools for composite-based PLS-SEM that will expand the skills of researchers and inform them on new methodologies for improving evaluation of theoretical models. Recently developed and proposed cross-validation approaches for model comparisons and benchmarking are reviewed and evaluated.

Findings

The results summarize next-generation prediction metrics that will substantially improve researchers' ability to assess and report the extent to which their theoretical models provide meaningful predictions. Improved prediction assessment metrics are essential to justify (practical) implications and recommendations developed on the basis of theoretical model estimation results.

Originality/value

The paper provides an overview of recently developed and proposed out-of-sample prediction metrics for composite-based PLS-SEM that will enhance the ability of researchers to demonstrate generalization of their findings from sample data to the population.
The impact of a sense of virtual community on online community: does online privacy concern matter?
Authors: Kim Jihye , Kim Hyung-Min , Kim Minseong
Published: October 2020

Purpose

The purpose of this study is to investigate the structural relationships between a sense of virtual community (SOVC), community satisfaction, community involvement, community commitment and alternative attractiveness in the online fan community context.

Design/methodology/approach

This study gathered and empirically analyzed data from 277 members of the online Super Junior fan community with frequency, reliability, confirmatory factor analyses and structural equation modeling (SEM) with Statistical Package for the Social Sciences (SPSS) 20.0 and AMOS 24.0.

Findings

The findings of SEM indicated that community satisfaction was significantly influenced by the four dimensions of SOVC, while community involvement was significantly affected by membership and fulfillment of needs. Also, community commitment and alternative attractiveness were significantly impacted by community satisfaction and community involvement. Lastly, privacy concern moderated the paths from influence to community satisfaction and from community satisfaction to community commitment, respectively.

Practical implications

The findings of this study should help online fan community administrators to reduce members' perception of alternative attractiveness (other fan communities) and to understand how privacy concern influences members' attitudes toward the online community.

Originality/value

In light of the findings, a greater understanding of the determinants of community commitment and alternative attractiveness along with privacy concern is critical in retaining virtual fan communities' members over the long-term.
The importance of appraisal in stressor–well-being relationships and the examination of personality traits as boundary conditions
Authors: Smith Rachel Williamson , DeNunzio Michael M. , Haynes Nicholas J. , Thiele Aneeqa
Published: October 2020

Purpose

The purpose of this study was to examine the mediating role of appraisals in three stressor–well-being relationships: (1) the mediating role of challenge appraisals in the relationship between daily skill demands and daily work engagement, (2) the mediating role of hindrance appraisals in the relationship between daily interruptions and daily depletion and (3) the mediating role of threat appraisals in the relationship between daily emotional demands and daily anxiety. We also examined the moderating influence of conscientiousness on the daily skill demands–challenge appraisal relationship, the moderating role of extraversion on the daily interruptions–hindrance appraisal relationship and the moderating influence of neuroticism on the daily emotional demands–threat appraisal relationship. Supplemental analyses also examined the moderating influence of the aforementioned personality traits on the respective direct effects of stressors on well-being outcomes.

Design/methodology/approach

We tested our hypotheses using a 5-days experience sampling design in a sample of 114 working adults and employed multilevel modeling.

Findings

All hypothesized mediating mechanisms were supported, however, the majority of moderation hypotheses were not supported.

Originality/value

We sought to extend the relatively recent advancement in the challenge–hindrance framework to provide additional evidence of the utility of distinguishing between challenge, hindrance and threat stressors. Although not supported, this is the one of the first papers to test the moderating influence of personality traits on the stressor–appraisal relationship.
Institutional duality incidence on subsidiaries: configuration, differentiation and avoidance strategies
Authors: Ahworegba Akiebe Humphrey , Estay Christophe , Garri Myropi
Published: October 2020

Purpose

To illustrate how threats of institutional duality (ID) incidence subsidiaries confront are converted to opportunities, by conceptualizing how subsidiaries attain operational legitimacy at both their headquarters (HQs) and host countries.

Design/methodology/approach

Using a systematic literature review, the authors build on institutional theories by analyzing the ID literature along its structure, main processes and outcomes. The authors configure frameworks of both HQ control systems and host countries' institutional threats, showing how subsidiaries contingently navigate across them using configuration, differentiation and avoidance strategies.

Findings

The authors’ findings show that “foresighted” subsidiaries attain operational legitimacy through configuration, differentiation and avoidance of threats incidental to ID, by strategizing along certain formal and informal institutional variables including legal, sociocultural and technical factors.

Originality/value

The authors propose “structural configuration of ID incidence” and “subsidiary path to legitimacy” frameworks. The former configures how the interaction between HQ and host countries' variables constitute ID incidence threats. The latter highlights how “foresighted” subsidiaries use configuration, differentiation and avoidance strategies to attain operational legitimacy.
NFL team revenue distribution and revenue sharing: a median voter theorem
Authors: Ehrlich Justin , Ghimire Shankar , Sanders Shane
Published: October 2020

Purpose

Revenue sharing is ubiquitous among North American professional sports leagues. Under pool revenue sharing, above-average revenue teams of a league effectively transfer revenues to below-average revenue teams. Herein, the authors find and prove that a league will vote into policy a pool revenue sharing arrangement if and only if mean team revenue is greater than presharing median revenue, where this condition is equivalent to the presence of positive nonparametric skewness in a league’s distribution of team revenues. This represents a median voter theorem for league revenue sharing.

Design/methodology/approach

The authors consider the case of revenue sharing for the National Football League (NFL), a league that pools and equally shares national revenues among member teams.

Findings

The authors find evidence of positive and significant nonparametric skewness in NFL team revenue distributions for the 2004–2016 seasons. This distribution is observed amid annual majority rule votes of League owners in favor of maintaining the incumbent pool revenue sharing model (as opposed to no team revenue sharing). Distribution of revenues – namely the existence of outlying large market NFL teams – appears to consistently explain the historical popularity of NFL revenue sharing.

Originality/value

The median voter theorem uncovered in the case of NFL applies to all professional sports leagues and can be used predictively as well as descriptively.