bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAlternative 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

AbstractPrevious 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

AbstractRetinal 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

AbstractSummaryMultiplexed 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 implementationhttps://registry.varianteffect.orgContactfritz.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

AbstractMechanistic 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.HighlightThis 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

AbstractThe 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.HighlightsRecollection is often defined as remembering the source or context of informationPrior work used ERPs to identify times when source memory did not have recollectionCurrent work replicated ERPs with added response times and measures of varianceRecollection was not evident in certain source memories, which had a negative ERPRecollection is independent of context and is more than just remembering sourcesGraphical 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

AbstractRadius 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

AbstractColorectal 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

AbstractDNA 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

ABSTRACTGerm 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.
Talking money at home: the value of family financial socialization
Authors: Zhao Haidong , Zhang Lini 
Published: October 2020

PurposeThe 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/approachUsing 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).FindingsThis 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 implicationsThe 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/valueThis 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

PurposeThis 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/approachThe 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.FindingsThis 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/valueThere 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

PurposeThe 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/approachThe 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.FindingsA 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/implicationsThe 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 implicationsThe 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/valueThe 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.