bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between PSD 95 and TRPV4 through PDZ domain controls TRPV4’s localization and activity
Authors: Lee Eun Jeoung , Kim Kiwol , Davaadorj Otgonnamjil , Shin Sung Hwa , Kang Sang Sun 
Published: July 2023

AbstractThe TRPV4 cation channel, is expressed in a broad range of tissues where it participates in generation of Ca2+signal and/or depolarization of membrane potential. Here, we identified post synaptic density protein 95 (PSD95) as an interacting protein of this epithelial Ca2+channel using confocal microscopy analysis and immunological assay. Using co-immunoprecipitation assays, we demonstrated that PSD95 was part of the TRPV4 protein complex. PSD95 protein was specifically associated with the C-terminal tail of TRPV4 to form a complex. A TRPV4 tail deletion mutant (ΔDAPL871: 4d) exhibited a diminished capacity to bind PSD95. Confocal microscopy analysis suggested that apical localization of TRPV4 required PSD95–TRPV4 interaction. Our data clearly suggest that formation of a complex between TRPV4 and PSD95 can regulate TRPV4 membrane localization. Both TRPV4 Ca2+channel and its autophagy activity of 4d were reduced by more than 80% compared to those of the TRPV4 wild type. Our observation suggests that PSD95–TRPV4 complex plays crucial roles in routing TRPV4 to the apical plasma membrane and maintaining its authentic Ca2+channel and biological function.CapsuleBackgroundTRPV4 contain putative PDZ tail motif (DAPL871).ResultsDeletion of TRPV4 tail PDZ motif fails to interact with PSD95 PDZ III domain.ConclusionTRPV4 tail is an authentic PDZ motif to interact with PSD95.SignificanceInteraction between TRPV4 and PSD95 requires for its proper biological functions.
Gestational and postnatal age associations for striatal tissue iron deposition in early infancy
Authors: Cabral Laura , Calabro Finn , Rasmussen Jerod , Foran Will , Moore Luci A. , Graham Alice , O’Connor Thomas G , Wadhwa Pathik D , Entringer Sonja , Fair Damien , Buss Claudia , Panigrahy Ashok , Luna Beatriz 
Published: July 2023

AbstractStriatal development is crucial for later motor, cognitive, and reward behavior, but age-related change in striatal physiology during the neonatal period remains understudied. An MRI-based measure of tissue iron deposition, T2*, is a non-invasive way to probe striatal physiology neonatally, linked to dopaminergic processing and cognition in children and adults. Striatal subregions have distinct functions that may come online at different time periods in early life. To identify if there are critical periods before or after birth, we measured if striatal iron accrued with gestational age at birth [range=34.57-41.85 weeks] or postnatal age at scan [range=5-64 days], using MRI to probe the T2* signal in N=83 neonates in three striatal subregions. We found iron increased with postnatal age in the pallidum and putamen but not the caudate. No significant relationship between iron and gestational age was observed. Using a subset of infants scanned at preschool age (N=26), we show distributions of iron shift between timepoints. In infants, the pallidum had the least iron of the three regions but had the most by preschool age. Together, this provides evidence of distinct change for striatal subregions, a possible differentiation between motor and cognitive systems, identifying a mechanism that may impact future trajectories.HighlightsNeonatal striatal tissue iron can be measured using the T2* signal from rsfMRInT2* changed with postnatal age in the pallidum and putamen but not in the caudatenT2* did not change with gestational age in any of the three regionsPatterns of iron deposition (nT2*) among regions shift from infancy to preschool
HOXDeRNA activates a cancerous transcription program and super-enhancers genome-wide
Authors: Deforzh Evgeny , Kharel Prakash , Karelin Anton , Ivanov Pavel , Krichevsky Anna M. 
Published: July 2023

ABSTRACTBackgroundThe origin and genesis of highly malignant and heterogenous glioblastoma brain tumors remain unknown. We previously identified an enhancer-associated long non-coding RNA, LINC01116 (named HOXDeRNA here), that is absent in the normal brain but is commonly expressed in malignant glioma. HOXDeRNA has a unique capacity to transform human astrocytes into glioma-like cells. This work aimed to investigate molecular events underlying the genome-wide function of this lncRNA in glial cell fate and transformation.ResultsUsing a combination of RNA-Seq, ChIRP-Seq, and ChIP-Seq, we now demonstrate that HOXDeRNA bindsin transto the promoters of genes encoding 44 glioma-specific transcription factors distributed throughout the genome and derepresses them by removing the Polycomb repressive complex 2 (PRC2). Among the activated transcription factors are the core neurodevelopmental regulators SOX2, OLIG2, POU3F2, and SALL2. This process requires an RNA quadruplex structure of HOXDeRNA that interacts with EZH2. Moreover, HOXDeRNA-induced astrocyte transformation is accompanied by the activation of multiple oncogenes such as EGFR, PDGFR, BRAF, and miR-21, and glioma-specific super-enhancers enriched for binding sites of glioma master transcription factors SOX2 and OLIG2.ConclusionsOur results demonstrate that HOXDeRNA overrides PRC2 repression of glioma core regulatory circuitry with RNA quadruplex structure. These findings help reconstruct the sequence of events underlying the process of astrocyte transformation and suggest a driving role for HOXDeRNA and a unifying RNA-dependent mechanism of gliomagenesis.
Substrate displacement of CK1 C-termini regulates kinase specificity
Authors: Cullati Sierra N. , Akizuki Kazutoshi , Chen Jun-Song , Gould Kathleen L. 
Published: July 2023

AbstractCK1 kinases participate in many signaling pathways; how these enzymes are regulated is therefore of significant biological consequence. CK1s autophosphorylate their C-terminal non-catalytic tails, and eliminating these modifications increases substrate phosphorylation in vitro, suggesting that the autophosphorylated C-termini act as inhibitory pseudosubstrates. To test this prediction, we comprehensively identified the autophosphorylation sites onSchizosaccharomyces pombeHhp1 and human CK1ε. Peptides corresponding to the C-termini interacted with the kinase domains only when phosphorylated, and phosphoablating mutations increased Hhp1 and CK1ε activity towards substrates. Interestingly, substrates competitively inhibited binding of the autophosphorylated tails to the substrate binding grooves. The presence or absence of tail autophosphorylation influenced the catalytic efficiency with which CK1s targeted different substrates, indicating that tails contribute to substrate specificity. Combining this mechanism with autophosphorylation of the T220 site in the catalytic domain, we propose a displacement specificity model to describe how autophosphorylation regulates substrate specificity for the CK1 family.
Decomposing a San Francisco Estuary microbiome using long read metagenomics reveals species and species- and strain-level dominance from picoeukaryotes to viruses
Authors: Lui Lauren M. , Nielsen Torben N. 
Published: July 2023

AbstractAlthough long read sequencing has enabled obtaining high-quality and complete prokaryotic genomes from metagenomes, many challenges still remain to completely decompose a metagenome into its constituent genomes. These challenges include obtaining enough biomass, high-molecular weight DNA extraction, determining the appropriate depth of sequencing, and bioinformatics challenges to separate closely related genomes. This study focuses on decomposing an estuarine water metagenome from USGS Station 36 in the South San Francisco Bay into its constituent genomes and counting the number of organisms present. To achieve this, we developed a new bead-based DNA extraction method, a novel bin refinement method, and sequenced the sample with 150 Gbases of nanopore sequencing. With our results, we were able to estimate that there are ∼500 bacteria and archaeal species in our sample, obtain 68 high-quality bins (>90% complete, <5% contamination, ≤5 contigs, no contigs shorter than 100 Kbases, and all ribosomal and necessary tRNA genes). Since we pre-filtered the sample at 11μm and then collected directly on to a 0.1μm filter, we also obtained many contigs of picoeukaryotes, environmental DNA of larger eukaryotes such as mammals, complete mitochondrial and chloroplast genomes, and detected ∼40,000 viral populations. This deep analysis of the taxonomy of the sample down to the strain and individual contig level allowed us to find that among picoeukaryotes, prokaryotes, and viruses there are likely only a few strains that comprise most of the species abundances. These results also indicate that to truly decompose a metagenome into its constituent genomes, we likely need 1Tbase of sequencing.If you are reading this preprint, know that this is the paper we wanted to write, but it will likely be shortened for submission to a journal.
Machine learning of enhancer-promoter specificity based on enhancer perturbation studies reveals a distinct class of enhancers
Authors: Barth Dylan , Cardwell Jonathan , Han Mira V. 
Published: July 2023

ABSTRACTMotivationUnderstanding the rules that govern enhancer-driven transcription remains a central unsolved problem in genomics. Now with multiple massively parallel enhancer perturbation assays published, there are enough data that we can utilize to learn to predict enhancer promoter relationships in a data driven manner.ResultsWe applied machine learning to one of the largest enhancer perturbation studies integrated with transcription factor and histone modification ChIP-seq. Based on the learned model, we confirmed previously reported rules governing enhancer driven transcription, and we gained some insights that generated new hypotheses, such as a novel role for protecting against replication-transcription conflict at the active enhancers in CHAMP1. We also identified a distinct class of enhancers that drives target promoter transcription, but is not in strong contact with the promoters. There were two clusters of such enhancers that regulatedATG2Aand the histone 1 cluster respectively. These enhancers were different from other typical enhancers, in that they had other strong enhancers nearby, and they also had strong H3K4me3 marks at the target promoters, both patterns that typically predict reduced enhancer influence, but here contributing in the opposite way. In summary, we find that integrating genomic assays with enhancer perturbation studies increases the accuracy of the model, and provides novel insights into the understanding of enhancer driven transcription.Availabilitythe trained models and the source code are available athttps://github.com/HanLabUNLV/abic.Contact:mira.han@unlv.edu
Structural insights into dual-antagonize mechanism of AB928 on adenosine A2receptors
Authors: Weng Yuan , Yang Xinyu , Zhang Qiansen , Chen Ying , Xu Yueming , Zhu Chenyu , Xie Qiong , Wang Yonghui , Yang Huaiyu , Liu Mingyao , Lu Weiqiang , Song Gaojie 
Published: July 2023

AbstractThe adenosine subfamily G protein-coupled receptors A2AR and A2BR were identified as promising candidates for cancer immunotherapy within recent years. One of the A2AR/A2BR dual antagonist, AB928, has progressed to phase II clinic trial for the treatment of rectal cancer. However, the precise mechanism underlying its dual-antagonistic properties remains elusive. Herein, we report crystal structures of A2AR in complex with AB928 and a selective A2AR antagonist, 2-118. The structures reveal a common binding mode on A2AR, wherein the ligands establish extensive interactions with residues from both the orthosteric pocket and the secondary pocket. Conversely, the cAMP assay together with molecular dynamics simulations conducted on both A2AR and A2BR indicate that the ligands adopt distinct binding modes on A2BR. Detailed analysis of their chemical structures suggests that AB928 can readily adapt to the A2BR pocket, while 2-118 cannot due to its intrinsic differences. This disparity potentially accounts for their divergent inhibitory efficacies between A2BR and A2AR. The findings from this study can serve as valuable structural templates for future development of selective or dual inhibitors targeting A2AR/A2BR in the context of cancer therapy.
A pedagogical approach optimization toward sustainable architectural technology education applied by massive open online courses
Authors: Zhu Bifeng , Zheng Yuan , Ding Manqi , Dai Jie , Liu Gebing , Miao Liting 
Published: July 2023

PurposeThe application of massive open online courses (MOOCs) helps integrate sustainable development goals (SDGs) into architectural curricula. The essence of MOOC development is building an education platform that promotes the sharing and continuing of global education resources.Design/methodology/approachThis study establishes a four-dimensional evaluation model based on the four characteristics of MOOCs. The quadrilateral area evaluation method is used to create an evaluation radar chart to comprehensively evaluate satisfaction and demand in the traditional teaching model of architectural technology. This study discusses whether the curriculum is suitable for the development of MOOCs and how to optimize the sustainable pedagogical mode according to its characteristics to meet future teaching needs and realize the sustainable development of education.FindingsSatisfaction evaluation found that current education is not open enough from the students' perspective; therefore, MOOCs enhance students' participation and significantly reduce future learning costs. Through demand evaluation, it was found that both teachers and students believed that the lack of direct and effective communication between them and the difficulty in ensuring the learning effect were problems that must be addressed in MOOCs.Originality/valueThis study focused on the sustainability of MOOCs in curriculum development. It emphasizes the combination of MOOCs' teaching modes and the course itself and provides specific guidance and suggestions for improving the course. It uses an evaluation method for objective analysis and visualization.
A critical appraisal of traditional methods of construction progress monitoring
Authors: Sami Ur Rehman Muhammad , Shafiq Muhammad Tariq , Ullah Fahim , Galal Ahmed Khaled 
Published: July 2023

PurposeThe purpose of this study is to investigate the current construction progress monitoring (CPM) process in relation to the contractual obligations, how project management teams carry out this activity in the field and why teams continue to adopt the current method. The study aims to provide a comprehensive understanding of the current monitoring process and its effectiveness, identify any shortcomings and propose recommendations for improvements that can lead to better project outcomes.Design/methodology/approachThe study conducted semi-structured interviews with 28 construction management practitioners to explore their views on contractual requirements, traditional progress monitoring practices and advanced monitoring methods. Thematic analysis was used to identify existing processes, practices and incentives for advanced monitoring.FindingsStandard construction contracts mandate current progress monitoring practices, which often rely on manual, document-centric and labor-intensive methods, leading to slow and erroneous progress reporting and project delays. Key barriers to adopting advanced tools include rigid contractual clauses, lack of incentives and the absence of reliable automated tools. A holistic automated approach that covers the entire CPM process, from planning to claim management, is needed as a viable alternative to traditional practices.Research limitations/implicationsThe study's findings can inform researchers, stakeholders and decision-makers about the existing monitoring practices and contribute to enhancing project management practices.Originality/valueThe study identified contractually mandated progress monitoring processes, traditional methods of collecting, transferring, analyzing and dispensing progress-related information and potential incentives and points of departure towards technologically advanced methods.
Seaweed as food: survey of the UK market and appraisal of opportunities and risks in the context of iodine nutrition
Authors: Redway Martha Lucy , Combet Emilie 
Published: July 2023

Purpose Seaweeds are gaining broader interest in Western societies through their use in product development and the health-food industry. High nutritional value, low carbon footprint and sustainability are key drivers for seaweed uptake in Europe; yet high iodine intake from seaweed remains a concern. This study seeks to identify seaweed food products available on the UK retail market between 2018 and 2021 and assess their safety in the context of iodine exposure.Design/methodology/approach Here, a market survey (n = 37–40 retailers) was conducted in three annual waves to evaluate seaweed food product availability in the UK. The iodine dose of products was estimated based on a comprehensive literature review of seaweed iodine content.Findings This study shows a young, dynamic market with 2.3-fold increase in seaweed food product availability since the last available published data (2015). Specific iodine content labelling remains uncommon, and median iodine doses in a single serving of food exceeded 400 µg in all years. Some products, especially seaweed supplements, provide iodine doses above the tolerable upper limit and upper level of tolerance.Originality/value This study presents the most contemporary and comprehensive overview of the market for seaweed food products in the UK. With increasing popularisation of seaweed as a food, this study highlights the need for improved dialogue amongst producers, retailers, legislators and public health specialists to address the risk of iodine excess, and the concurrent scope for processing methods to reduce the iodine content in seaweeds.
A dynamic material distribution scheduling of automotive assembly line considering material-handling errors
Authors: Zhou Binghai , Wen Mingda 
Published: July 2023

PurposeIn a kitting supply system, the occurrence of material-handling errors is unavoidable and will cause serious production losses to an assembly line. To minimize production losses, this paper aims to present a dynamic scheduling problem of automotive assembly line considering material-handling mistakes by integrating abnormal disturbance into the material distribution problem of mixed-model assembly lines (MMALs).Design/methodology/approachA multi-phase dynamic scheduling (MPDS) algorithm is proposed based on the characteristics and properties of the dynamic scheduling problem. In the first phase, the static material distribution scheduling problem is decomposed into three optimization sub-problems, and the dynamic programming algorithm is used to jointly optimize the sub-problems to obtain the optimal initial scheduling plan. In the second phase, a two-stage rescheduling algorithm incorporating removing rules and adding rules was designed according to the status update mechanism of material demand and multi-load AGVs.FindingsThrough comparative experiments with the periodic distribution strategy (PD) and the direct insertion method (DI), the superiority of the proposed dynamic scheduling strategy and algorithm is verified.Originality/valueTo the best of the authors’ knowledge, this study is the first to consider the impact of material-handling errors on the material distribution scheduling problem when using a kitting strategy. By designing an MPDS algorithm, this paper aims to maximize the absorption of the disturbance caused by material-handling errors and reduce the production losses of the assembly line as well as the total cost of the material transportation.
An application of data-driven modeling for hydroelasticity of an elastically supported semi-circular pipe conveying fluid
Authors: Xu Jianhang , Li Peng , Yang Yiren 
Published: July 2023

PurposeThe paper aims to develop an efficient data-driven modeling approach for the hydroelastic analysis of a semi-circular pipe conveying fluid with elastic end supports. Besides the structural displacement-dependent unsteady fluid force, the steady one related to structural initial configuration and the variable structural parameters (i.e. the variable support stiffness) are considered in the modeling.Design/methodology/approachThe steady fluid force is treated as a pipe preload, and the elastically supported pipe-fluid model is dealt with as a prestressed hydroelastic system with variable parameters. To avoid repeated numerical simulations caused by parameter variation, structural and hydrodynamic reduced-order models (ROMs) instead of conventional computational structural dynamics (CSD) and computational fluid dynamics (CFD) solvers are utilized to produce data for the update of the structural, hydrodynamic and hydroelastic state-space equations. Radial basis function neural network (RBFNN), autoregressive with exogenous input (ARX) model as well as proper orthogonal decomposition (POD) algorithm are applied to modeling these two ROMs, and a hybrid framework is proposed to incorporate them.FindingsThe proposed approach is validated by comparing its predictions with theoretical solutions. When the steady fluid force is absent, the predictions agree well with the “inextensible theory”. The pipe always loses its stability via out-of-plane divergence first, regardless of the support stiffness. However, when steady fluid force is considered, the pipe remains stable throughout as flow speed increases, consistent with the “extensible theory”. These results not only verify the accuracy of the present modeling method but also indicate that the steady fluid force, rather than the extensibility of the pipe, is the leading factor for the differences between the in- and extensible theories.Originality/valueThe steady fluid force and the variable structural parameters are considered in the data-driven modeling of a hydroelastic system. Since there are no special restrictions on structural configuration, steady flow pattern and variable structural parameters, the proposed approach has strong portability and great potential application for other hydroelastic problems.
Designing an efficient smoothed point interpolation method for modeling slope deformation
Authors: Qin Jiayu , Xu Nengxiong , Mei Gang 
Published: July 2023

PurposeIn this paper, the smoothed point interpolation method (SPIM) is used to model the slope deformation. However, the computational efficiency of SPIM is not satisfying when modeling the large-scale nonlinear deformation problems of geological bodies.Design/methodology/approachIn this paper, the SPIM is used to model the slope deformation. However, the computational efficiency of SPIM is not satisfying when modeling the large-scale nonlinear deformation problems of geological bodies.FindingsA simple slope model with different mesh sizes is used to verify the performance of the efficient face-based SPIM. The first accelerating strategy greatly enhances the computational efficiency of solving the large-scale slope deformation. The second accelerating strategy effectively improves the convergence of nonlinear behavior that occurred in the slope deformation.Originality/valueThe designed efficient face-based SPIM can enhance the computational efficiency when analyzing large-scale nonlinear slope deformation problems, which can help to predict and prevent potential geological hazards.