bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two distinct networks containing position-tolerant representations of actions in the human brain
Authors: Yargholi Elahé , Hossein-Zadeh Gholam-Ali , Vaziri-Pashkam Maryam 
Published: June 2021

AbstractHumans can recognize other people’s actions in the social environment. This action recognition ability is rarely hindered by the movement of people in the environment. The neural basis of this tolerance to changes in the position of observed actions is not fully understood. Here, we aimed to identify brain regions capable of generalizing representations of actions across different positions and investigate the representational content of these regions. fMRI data were recorded from twenty-two subjects while they were watching video clips of ten different human actions in Point Light Display format. Each stimulus was presented in either the upper or the lower visual fields. Multivoxel pattern analysis and a searchlight technique were employed to identify brain regions that contain position-tolerant action representation: linear support vector machine classifiers were trained with fMRI patterns in response to stimuli presented in one position and tested with stimuli presented in another position. Results of this generalization test showed above-chance classification in the left and right lateral occipitotemporal cortex, right intraparietal sulcus, and right post-central gyrus. To explore the representational content of these regions, we constructed models based on the objective measures of movements and human subjective judgments about actions. We then evaluated the brain similarity matrix from the cross-position classification analysis based on these models. Results showed cross-position classifications in the lateral occipito-temporal ROIs were more strongly related to the subjective judgments, while those in the dorsal parietal ROIs were more strongly related to the objective movements. An ROI representational similarity analysis further confirmed the separation of the dorsal and lateral regions. These results provide evidence for two networks that contain abstract representations of human actions with distinct representational content.
LongStitch: High-quality genome assembly correction and scaffolding using long reads
Authors: Coombe Lauren , Li Janet X , Lo Theodora , Wong Johnathan , Nikolic Vladimir , Warren René L , Birol Inanc 
Published: June 2021

AbstractBackgroundGenerating high-quality de novo genome assemblies is foundational to the genomics study of model and non-model organisms. In recent years, long-read sequencing has greatly benefited genome assembly and scaffolding, a process by which assembled sequences are ordered and oriented through the use of long-range information. Long reads are better able to span repetitive genomic regions compared to short reads, and thus have tremendous utility for resolving problematic regions and helping generate more complete draft assemblies. Here, we present LongStitch, a scalable pipeline that corrects and scaffolds draft genome assemblies exclusively using long reads.ResultsLongStitch incorporates multiple tools developed by our group and runs in up to three stages, which includes initial assembly correction (Tigmint-long), followed by two incremental scaffolding stages (ntLink and ARKS-long). Tigmint-long and ARKS-long are misassembly correction and scaffolding utilities, respectively, previously developed for linked reads, that we adapted for long reads. Here, we describe the LongStitch pipeline and introduce our new long-read scaffolder, ntLink, which utilizes lightweight minimizer mappings to join contigs. LongStitch was tested on short and long-read assemblies of three different human individuals using corresponding nanopore long-read data, and improves the contiguity of each assembly from 2.0-fold up to 304.6-fold (as measured by NGA50 length). Furthermore, LongStitch generates more contiguous and correct assemblies compared to state-of-the-art long-read scaffolder LRScaf in most tests, and consistently runs in under five hours using less than 23GB of RAM.ConclusionsDue to its effectiveness and efficiency in improving draft assemblies using long reads, we expect LongStitch to benefit a wide variety of de novo genome assembly projects. The LongStitch pipeline is freely available at https://github.com/bcgsc/longstitch.
The membrane associated accessory protein is an adeno-associated viral egress factor
Authors: Elmore Zachary C. , Patrick Havlik L. , Oh Daniel K. , Vincent Heather A. , Asokan Aravind 
Published: June 2021

AbstractAdeno-associated viruses (AAV) rely on helper viruses to transition from latency to lytic infection. Some recombinant AAV serotypes are secreted in a pre-lytic manner as extracellular vesicle (EV)-associated particles, although mechanisms underlying such are unknown. Here, we discover that the membrane-associated accessory protein (MAAP), expressed from a (+1) frameshifted open reading frame (ORF) in the AAV capsid (cap) gene, is a novel viral egress factor. MAAP contains a highly conserved, cationic amphipathic domain critical for AAV secretion. Wild type or recombinant AAV with a mutated MAAP start site (MAAPΔ) show markedly attenuated secretion and correspondingly, increased intracellular retention. Trans-complementation with recombinant MAAP restored extracellular secretion of multiple AAV/MAAPΔ serotypes. MAAP is sorted into recycling Rab11+ vesicles and strongly associates with EV markers upon fractionation. In addition to characterizing a novel viral egress factor, these studies highlight a prospective engineering platform to modulate secretion of AAV vectors or other EV-associated cargo.
A Robust High-throughput Fluorescent Polarization Assay for the Evaluation and Screening of SARS-CoV-2 Fusion Inhibitors
Authors: Yin Xinjian , Chen Litong , Yuan Siwen , Liu Lan , Gao Zhizeng 
Published: June 2021

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious threat to global health. One attractive antiviral target is the membrane fusion mechanism employed by the virus to gain access to the host cell. Here we report a robust protein-based fluorescent polarization assay, that mimicking the formation of the six-helix bundle (6-HB) process during the membrane fusion, for the evaluation and screening of SARS-CoV-2 fusion Inhibitors. The IC50 of known inhibitors, HR2P, EK1, and Salvianolic acid C (Sal C) were measured to be 6 nM, 2.5 nM, and 8.9 µM respectively. In addition, we found Sal A has a slightly lower IC50 (3.9 µM) than Sal C. Interesting, simple caffeic acid can also disrupt the formation of 6-HB with sub-mM concentration. A pilot high throughput screening (HTS) a small marine natural product library validates the assay with a Z’ factor close to 0.8. We envision the current assay provides a convenient way to screen SARS-CoV-2 fusion inhibitor and assess their binding affinity.
Benchmarking UMI-based single cell RNA-sequencing preprocessing workflows
Authors: You Yue , Tian Luyi , Su Shian , Dong Xueyi , Jabbari Jafar S , Hickey Peter F , Ritchie Matthew E 
Published: June 2021

Single-cell RNA sequencing (scRNA-seq) technologies and associated analysis methods have undergone rapid development in recent years. This includes methods for data preprocessing, which assign sequencing reads to genes to create count matrices for downstream analysis. Several packaged preprocessing workflows have been developed that aim to provide users with convenient tools for handling this process. How different preprocessing workflows compare to one another and influence downstream analysis has been less well studied.Here, we systematically benchmark the performance of 9 end-to-end preprocessing workflows (Cell Ranger, Optimus, salmon alevin, kallisto bustools, dropSeqPipe, scPipe, zUMIs, celseq2 and scruff) using datasets with varying levels of biological complexity generated on the CEL-Seq2 and 10x Chromium platforms. We compare these workflows in terms of their quantification properties directly and their impact on normalization and clustering by evaluating the performance of different method combinations. We find that lowly expressed genes are discordant between workflows and observe that some workflows have systematic biases towards particular classes of genomics features. While the scRNA-seq preprocessing workflows compared varied in their detection and quantification of genes across datasets, after downstream analysis with performant normalization and clustering methods, almost all combinations produced clustering results that agreed well with the known cell type labels that provided the ground truth in our analysis.In summary, the choice of preprocessing method was found to be less influential than other steps in the scRNA-seq analysis process. Our study comprehensively compares common scRNA-seq preprocessing workflows and summarizes their characteristics to guide workflow users.
Whole-genome sequencing and analysis of two azaleas, Rhododendron ripense and Rhododendron kiyosumense
Authors: Shirasawa Kenta , Kobayashi Nobuo , Nakatsuka Akira , Ohta Hideya , Isobe Sachiko 
Published: June 2021

ABSTRACTTo enhance the genomics and genetics of azalea, the whole-genome sequences of two species of Rhododendron were determined and analyzed in this study: Rhododendron ripense, the cytoplasmic donor and ancestral species of large-flowered and evergreen azalea cultivars, respectively; and Rhododendron kiyosumense, a native of Chiba prefecture (Japan) seldomly bred and cultivated. A chromosome-level genome sequence assembly of R. ripense was constructed by single-molecule real-time (SMRT) sequencing and genetic mapping, while the genome sequence of R. kiyosumense was assembled using the single-tube long fragment read (stLFR) sequencing technology. The R. ripense genome assembly contained 319 contigs (506.7 Mb; N50 length: 2.5 Mb) and was assigned to the genetic map to establish 13 pseudomolecule sequences. On the other hand, the genome of R. kiyosumense was assembled into 32,308 contigs (601.9 Mb; N50 length: 245.7 kb). A total of 34,606 genes were predicted in the R. ripense genome, while 35,785 flower and 48,041 leaf transcript isoforms were identified in R. kiyosumense through Iso-Seq analysis. Overall, the genome sequence information generated in this study enhances our understanding of genome evolution in the Ericales and reveals the phylogenetic relationship of closely-related species. This information will also facilitate the development of phenotypically attractive azalea cultivars.
Impaired SorLA maturation and trafficking as a new mechanism for SORL1 missense variants in Alzheimer disease
Authors: Rovelet-Lecrux Anne , Feuillette Sebastien , Miguel Laetitia , Schramm Catherine , Pernet Ségolène , Ségalas-Milazzo Isabelle , Guilhaudis Laure , Rousseau Stéphane , Riou Gaëtan , Frébourg Thierry , Campion Dominique , Nicolas Gaël , Lecourtois Magalie 
Published: June 2021

ABSTRACTThe SorLA protein, encoded by the SORL1 gene, is a major player in Alzheimer’s disease (AD) pathophysiology. Functional and genetic studies demonstrated that SorLA deficiency results in increased production of Aβ peptides, and thus a higher risk of AD. A large number of SORL1 missense variants have been identified in AD patients, but their functional consequences remain largely undefined. Here, we identified a new pathophysiological mechanism, by which rare SORL1 missense variants identified in AD patients result in altered maturation and trafficking of the SorLA protein. An initial screening, based on the overexpression of 71 SorLA variants in HEK293 cells, revealed that 15 of them (S114R, R332W, G543E, S564G, S577P, R654W, R729W, D806N, Y934C, D1535N, D1545E, P1654L, Y1816C, W1862C, P1914S) induced a maturation and trafficking-deficient phenotype. Three of these variations (R332W, S577P, and R654W) and two maturation-competent variations (S124R and N371T) were further studied in details in CRISPR/Cas9-modified hiPSCs. When expressed at endogenous levels, the R332W, S577P, and R654W SorLA variants also showed a maturation defective profile. We further demonstrated that these variants were largely retained in the endoplasmic reticulum, resulting in a reduction in the delivery of SorLA mature protein to the plasma membrane and to the endosomal system. Importantly, expression of the R332W and R654W variants in hiPSCs was associated with a clear increase of Aβ secretion, demonstrating a loss-of-function effect of these SorLA variants regarding this ultimate readout, and a direct link with AD pathophysiology. Furthermore, structural analysis of the impact of missense variations on SorLA protein indicated that impaired cellular trafficking of SorLA protein could be due to subtle variations of the protein 3D structure resulting from changes in the interatomic interactions.
Mental practice modulates functional connectivity between the cerebellum and the primary motor cortex
Authors: Monany Dylan Rannaud , Lebon Florent , Dupont William , Papaxanthis Charalambos 
Published: June 2021

AbstractOur brain has the extraordinary capacity to improve motor skills through mental practice. Conceptually, this ability is attributed to internal forward models, which are neural networks that can predict the sensory consequences of motor commands. While the cerebellum is considered as a potential locus of internal forward models, evidence for its involvement in mental practice is missing. In our study, we employed single and dual transcranial magnetic stimulation technique to probe the level of corticospinal excitability and of cerebellar-brain inhibition, respectively, before and after a mental practice session or a control session. Motor skills (i.e., accuracy and speed) were measured using a sequential finger tapping-task. Here, we show that mental practice enhances both speed and accuracy. In parallel, the functional connectivity between the cerebellum and the primary motor cortex changes, with less inhibition from the first to the second, expressing the existence of neuroplastic changes within the cerebellum after mental practice. These findings reveal that the corticocerebellar loop is a major neural circuit for skill improvement after mental practice.
A computational screen for alternative genetic codes in over 250,000 genomes
Authors: Shulgina Yekaterina , Eddy Sean R. 
Published: June 2021

AbstractThe genetic code has been proposed to be a “frozen accident”, but the discovery of alternative genetic codes over the past four decades has shown that it can evolve to some degree. Since most examples were found anecdotally, it is difficult to draw general conclusions about the evolutionary trajectories of codon reassignment and why some codons are affected more frequently. To fill in the diversity of genetic codes, we developed Codetta, a computational method to predict the amino acid decoding of each codon from nucleotide sequence data. We surveyed the genetic code usage of over 250,000 bacterial and archaeal genome sequences in GenBank and discovered five new reassignments of arginine codons (AGG, CGA, and CGG), representing the first sense codon changes in bacteria. In a clade of uncultivated Bacilli, the reassignment of AGG to become the dominant methionine codon likely evolved by a change in the amino acid charging of an arginine tRNA. The reassignments of CGA and/or CGG were found in genomes with low GC content, an evolutionary force which likely helped drive these codons to low frequency and enable their reassignment.
Identification of SGLT2 inhibitor Ertugliflozin as a treatment for COVID-19 using computational and experimental paradigm
Authors: Saxena Shalini , Meher Kranti , Rotella Madhuri , Vangala Subhramanyam , Chandran Satish , Malhotra Nikhil , Palakodeti Ratnakar , Voleti Sreedhara R , Saxena Uday 
Published: June 2021

AbstractDrug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The RBD domain of SARS-CoV-2 Spike protein is a promising drug target due to its pivotal role in viral-host attachment. These specific structural domains can be targeted with small molecules or drug to disrupt the viral attachment to the host proteins. In this study, FDA approved Drugbank database were screened using a virtual screening approach and computational chemistry methods. Five drugs were short listed for further profiling based on docking score and binding energies. Further these selected drugs were tested for their in vitro biological activity. There was significant correlation between the prediction from computational studies and the actual RBD-ACE2 binding inhibition by the drugs. Then, we performed a series of studies that mimic some of the biological events seen in COVID-19 patients such as secretion of IL1β, presentation of a more thrombogenic endothelium by production of thrombomodulin and accumulation of inflammatory cells such as monocytes in the lungs. Of all the drugs, most promising drug was Ertugliflozin which is used for type-2 diabetes. This drug possesses several desired properties and may be a good candidate for immediate repurposing for treatment of COVID-19.
Dexamethasone promotes breast cancer stem cells in obese and not lean mice
Authors: Annett Stephanie , Fox Orla Willis , Vareslija Damir , Robson Tracy 
Published: June 2021

AbstractObesity is highly prevalent in breast cancer patients and it is associated with increased recurrence and breast cancer specific mortality. Glucocorticoid (GC) use, in addition to obesity is associated with promoting breast cancer metastasis through activation of stemness-related pathways. Therefore, we utilised the synergetic allograft E0771 breast cancer model to investigate if treatment with GCs had differential effects on promoting cancer stem cells in lean and diet-induced obese mice. Indeed, both lean mice treated with dexamethasone and obese mice with no treatment had no effect on the ex vivo colony forming ability, mammosphere formation or ALDH bright subpopulation. However, treatment of obese mice with dexamethasone resulted in a significant increase in ex vivo colony formation, mammosphere formation, ALDH bright subpopulation and expression of pluripotency transcription factors. GC transcriptionally regulated genes were not altered in the dexamethasone treated groups compared to treatment controls. In summary, these results provide initial evidence that obesity presents a higher risk of GC induced cancer stemness via non-genomic GC signalling which is of potential translational significance.
Strengthened passivation and mechanism of 316L stainless steel in hot diluted sulfuric acid solution by connecting to Pd electrode
Authors: Zhang Huizhong , Zuo Yu , Ju Pengfei , Zhang Jian , Zhao Xuhui , Tang Yuming , Zhang Xiaofeng 
Published: June 2021

Purpose
The purpose of this paper is to study the variations of composition and properties of the passive film on 316 L stainless steel surface in 80°C, 0.5 mol L-1 H2SO4 + 2 mg L-1 NaF solution, is helpful to understand the mechanisms of corrosion resistancethe of plated Pd on 316 L ss.

Design/methodology/approach
The variations of composition and properties of the passive film on 316 L stainless steel surface in 80°C, 0.5 mol L-1 H2SO4 + 2 mg L-1 NaF solution after connected to Pd electrode were studied with methods of potential monitor, X-ray photoelectron spectroscopy analysis and electrochemical impedance spectrum (EIS) measurement.

Findings
By connecting to a Pd electrode, the potential of the SS sample increased from the active region to the passive region. By connecting to the Pd electrode, the contents of Cr, Cr(OH)3 and Fe3O4 in passive film increased obviously. With increased Pd/SS area ratio, the Cr(OH)3 content in passive film increased but the Fe3O4 content changed little. The results show that after connecting to Pd the corrosion resistance of the passive film on 316 L stainless steel increases obviously, which may be attributed to the more compact passive film because of higher Cr, Cr(OH)3 and Fe3O4 contents and less point defects in the film.

Originality/value
The effects and mechanism of Pd on passivation of SS was studied.
Homo economicus? An investigation of factors influencing perceived comfort of choosing paper-based triple stimulus vouchers
Authors: Tan Wee Kheng , Liang Hao-Jen 
Published: June 2021

PurposeTo alleviate the effects of coronavirus disease 2019 (COVID-19) on the economy, Taiwan introduced a stimulus package in the form of triple stimulus vouchers. Despite intense promotion to opt for the vouchers in digital form, Taiwanese public overwhelmingly chose the paper form. This study considers the reasons that influenced their decision comfort in choosing paper rather than digital vouchers based on two categories: rational (promotion depth and ease of use) and behavioral economics factors (analysis paralysis, mental accounting related to ease of tracking expenses, social influence and payment habits).Design/methodology/approachPartial least squares (PLS) method was utilized to analyze survey information obtained from 183 individuals who chose paper vouchers.FindingsIndividuals consider rational and behavioral economic factors in their perception of decision comfort while choosing paper over digital vouchers. Decision comfort is driven more by behavioral economics than rational factors such as ease of use. Interestingly, analysis paralysis related to paper vouchers has the greatest impact, but it positively influences decision comfort, indicating that Taiwanese people view paper vouchers as a safe haven in the midst of uncertainties and information overload. Therefore, when designing public policies or promotional campaigns, possible behavior outcomes should be considered from both rational and behavioral economic perspectives.Originality/valueThis study provides insights into the dynamics of how individuals arrive at their decision of opting paper vouchers over digital ones and offers theoretical contributions related to system adoption and behavioral economics.
Emerging safety risks from public facilities: a field study for ablution spaces in mosques
Authors: Kim In-Ju , Bendak Salaheddine 
Published: June 2021

Purpose
Muslims require an exclusive ablution space for preparing for daily prayers in mosques. Ablution floors seem to entail design challenges since they are often encountered in lubricated conditions from worshippers’ body cleaning manoeuvers. Accordingly, fall risks on saturated surfaces of ablution floors would be a major issue to Muslim worshippers. Thus, the purpose of this study is to investigate the safety status of mosque ablution floors in terms of slip resistance properties and surface texture.

Design/methodology/approach
Fifteen mosques in Dubai and Sharjah cities of the UAE were randomly chosen to investigate the safety conditions of ablution spaces. In-situ slip-resistance properties and surface finishes of each ablution floor were measured under clean, wet, and soapy conditions at two different volumes of traffic areas: heavy- and non-traffic. Surface finishes of ablution floors were also measured and analysed.

Findings
Outcomes from this study evidently showed that the inspected ablution floors were not currently protected against falls, especially under wet and soapy environments. Surface analyses identified that the present ablution floors have extremely flat surfaces (? 2 µm in the Ra parameter) so they require significant improvements against fall risks.

Originality/value
Regardless of the magnitude of this issue, it is scarce to attain any published study on ablution floors’ fall incidence and avoidance plans in the scientific and technical literature. There are also no officially and publicly available data on fall incidents from ablution places in mosques. Findings from this study would be a great step forward to establish safer ablution floors for Muslim prayers.