bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal dynamics of short-term neural adaptation across human visual cortex
Authors: Brands Amber M. , Devore Sasha , Devinsky Orrin , Doyle Werner , Flinker Adeen , Friedman Daniel , Dugan Patricia , Winawer Jonathan , Groen Iris I. A. 
Published: September 2023

AbstractNeural responses in visual cortex adapt to prolonged and repeated stimuli. While adaptation occurs across the visual cortex, it is unclear how adaptation patterns and computational mechanisms differ across the visual hierarchy. Here we characterize two signatures of short-term neural adaptation in time-varying intracranial electroencephalography (iEEG) data collected while participants viewed naturalistic image categories varying in duration and repetition interval. Ventraland lateral-occipitotemporal cortex exhibit slower and prolonged adaptation to single stimuli and slower recovery from adaptation to repeated stimuli compared to V1-V3. For category-selective electrodes, recovery from adaptation is slower for preferred than non-preferred stimuli. To model neural adaptation we augment our delayed divisive normalization (DN) model by scaling the input strength as a function of stimulus category, enabling the model to accurately predict neural responses across multiple image categories. The model fits suggest that differences in adaptation patterns arise from slower normalization dynamics in higher visual areas interacting with differences in input strength resulting from category selectivity. Our results reveal systematic differences in temporal adaptation of neural population responses across the human visual hierarchy and show that a single computational model of history-dependent normalization dynamics, fit with area-specific parameters, accounts for these differences.Author summaryNeural responses in visual cortex adapt over time, with reduced responses to prolonged and repeated stimuli. Here, we examine how adaptation patterns differ across the visual hierarchy in neural responses recorded from human visual cortex with high temporal and spatial precision. To identify possible neural computations underlying short-term adaptation, we fit the response time courses using a temporal divisive normalization model. The model accurately predicts prolonged and repeated responses in lower and higher visual areas, and reveals differences in temporal adaptation across the visual hierarchy and stimulus categories. Our model suggests that differences in adaptation patterns result from differences in divisive normalization dynamics. Our findings shed light on how information is integrated in the brain on a millisecond-time scale and offer an intuitive framework to study the emergence of neural dynamics across brain areas and stimuli.
Transient structural properties of the Rho GDP-dissociation inhibitor
Authors: Gomez Sara Medina , Visco Ilaria , Merino Felipe , Bieling Peter , Linser Rasmus 
Published: September 2023

AbstractRho GTPases are master spatial regulators of the cytoskeleton that control a wide range of cellular processes. Their inactivation by removal from cellular membranes involves the stepwise formation of a stable complex with guanine nucleotide dissociation inhibitors (RhoGDIs), for which process the RhoGDI N-terminus is indispensable. The formation of this interface has been thought to emerge from an intrinsically disordered state of RhoGDI in its free, apo form. Here we use tailored solution NMR analyses, molecular dynamics simulations, and biochemical essays to pinpoint the site-specific structural features of full-length RhoGDI1 before and after binding its GTPase client Cdc42. In contrast to the current mechanistic understanding, a diverse set of NMR data unequivocally shows that the structural properties of the GDI N-terminus seen in crystal structures of the complex with GTPases already exist as largely preformed features in free, apo GDI. Even more interestingly, the required structural properties are imposed onto the terminus context-specifically by modulating interactions with the surface of the folded C-terminal domain. Lastly, upon Cdc42 binding, the flexibility of the N-terminus and its secondary-structural propensities are not largely abrogated. These observations change the textbook picture of the mechanism of membrane extraction of the GTPase. Rather than a disorder-to-order transition upon binding, an active role of the N-terminus with differentially preformed structural properties, suitably modulated by the specific surrounding along the multi-step process, seems required to leverage the intricate and highly selective extraction process.
Left-right asymmetry is formed in the basal bodies of the mouse node cilia in a cilia motility-dependent manner
Authors: Yoke Hiroshi , Taniguchi Atsushi , Nonaka Shigenori 
Published: September 2023

AbstractLaterality of the shapes and arrangements of the visceral organs in mice is determined in the node, a small cavity found at the ventral side of 7.5 dpc (days post coitum) embryos. On the node cells, motile cilia which are tilted toward the posterior side of the embryos show clockwise movement and thus produce fluid flow in the node toward the left side of the embryos. This left-ward flow regulates left/right (L/R) asymmetric gene expressions and L/R asymmetric morphogenesis in later stages. Structurally, node cilia have the characteristics of primary cilia and their basal body (mother centriole) is accompanied by a daughter centriole. Here, to obtain insights into the process of symmetry breaking by node cilia, we investigated whether the structure of the cilia themselves have L/R asymmetry, and found that positions of the daughter centrioles become biased to the right side of the mother centrioles in a stage-dependent manner. We found that this L/R asymmetry of the basal bodies is absent inivmutant mice, in which node cilia are immotile, suggesting that formation of this L/R asymmetry in the basal bodies requires cilia motility. It has been reported that culturing embryos in a flow chamber with artificial counter-flow, which is toward the opposite direction to the endogenous leftward flow in the node, results in reversed laterality of the visceral organs in later stages. However, we found that applying such artificial counter-flow did not reverse the L/R asymmetry of the basal bodies, and the daughter centrioles were still biased to the right side of the mother centrioles, suggesting that the L/R asymmetry of the basal bodies is formed independently from the direction of the fluid flow in the node and that it is independent from the laterality of the visceral organs. Although the biological significance of this phenomenon is unknown so far, these results suggest that node cilia have a previously unknown mechanism to produce L/R asymmetry in the basal bodies inside the cells in early development, independently from the canonical fluid flow-dependent L/R determining pathway.
Discovery of peptides for targeted delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia
Authors: Soto Melissa R. , Lewis Mae M. , Leal Jasmim , Pan Yuting , Mohanty Rashmi P. , Peng Sophie , Dong Tony , Ghosh Debadyuti 
Published: September 2023

AbstractFor cystic fibrosis (CF) patients, a lung targeted gene therapy would significantly alleviate pulmonary complications associated with morbidity and mortality. However, mucus in the airways and cell entry pose huge delivery barriers for local gene therapy. Here, we used phage display technology to select for and identify mucus- and cell-penetrating peptides against primary human bronchial epithelial cells (pHBECs) from CF patients cultured at air-liquid interface (ALI). At ALI, pHBECs produce mucus and reflect CF disease pathology, making it a clinically relevant model. Using this model, we discovered a lead candidate peptide, and incorporated it into lipid nanoparticles (LNPs) to deliver mRNA to pHBECs and mouse lungsin vivo. Compared to LNPs without our peptide, peptide-LNPs demonstrated 7.8-fold and 4.8-fold higher mRNA expressionin vitroandin vivo, respectively. Since gene delivery to pHBECs is a significant challenge, we are encouraged by these results and anticipate that our peptide could be used to successfully deliver CF gene therapies in future work.
Microsporidia Ser/Thr Protein Phosphatase PP1 Targets DCs MAPK Pathway and Impairs Immune Functions
Authors: Bao Jialing , Tang Yunlin , Chen Yebo , Jin Jiangyan , Wang Xue , An Guozhen , Cao Lu , Mo Biying , Zhang Huarui , Cheng Gong , Pan Guoqing , Zhou Zeyang 
Published: September 2023

AbstractMicrosporidia are difficult to completely eliminate. Their persistence may disrupt host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia infection upon dendritic cells (DCs). We used the zoonotic microsporidia species,Enterocytozoon hellem, in our studies.In vivoexperiments showed thatE. hellem-infected mice were more susceptible to further pathogenic challenges. DCs were identified as the most affected group of cells.In vitroassays revealed thatE. helleminfection impaired the immune functions of DCs as reflected by down-regulation of cytokine expression, lower extent of maturation and antigen presentation.E. helleminfection decreased the ability of DCs to prime and stimulate T cells, thereby hampering host immune cell functions. We further demonstrate thatE. hellemSer/Thr protein phosphatase PP1 directly interacts with host p38α(MAPK14) to manipulate the p38α (MAPK14)/NFAT-5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs immune functions. The emerging of microsporidiosis may be great threat to public health.HighlightsPersistence of Microsporidia within host impairs dendritic cell functions such as phagocytosis, maturation, antigen presentation and T cell priming, thereby disrupting both innate and adaptive immunities and making the host more vulnerable to secondary infectionsMicrosporidia impairs DCs function via Serine/Threonine Protein Phosphatase PP1 directly targeting DCs p38α/MAPK pathwayLatent Microsporidia infection and persistence is a great threat to public health when assessing acute and emerging pathogen risk
Defining the SPCA2C interactome identifies unique links to Store-Operated Ca2+Entry
Authors: Samardzija Petra , Fenech Melissa A , Lang Ryann , Carter McKenzie C , Chen Stephanie , Shi Selina , Stathopulos Peter B , Pin Christopher L 
Published: September 2023

AbstractCalcium (Ca2+) is critical for normal cell function and several protein networks are required for Ca2+signaling. In the pancreas, regulated changes in cytosolic Ca2+allow for the exocytosis of zymogen granules and altered Ca2+signaling underlies pancreatic pathologies. Previously, our laboratory showed a pancreas-specific isoform of secretory pathway Ca2+-ATPase 2 (SPCA2C) affects multiple pathways involved in Ca2+homeostasis. The goal of this study was to define the SPCA2C interactome that contributes to these processes. Using proximity-dependent biotin identification, BioID, we expressed SPCA2C-BirA*HAin HEK293 cells with constitutive Orai1 expression.In silicomodeling of SPCA2C showed a highly dynamic cytosolic C-terminus, revealing a putative site for interactions and was selected for BirA* fusion. 150 candidate SPCA2C interactors were identified. Gene Ontology and KEGG Pathway analyses supported localization of SPCA2C to the endoplasmic reticulum as well as function in Ca2+signaling and suggested roles in vesicular transport. SPCA2C interactions with stromal interaction molecule 1 (STIM1), extended synaptotagmin-1 (ESYT1), and aspartate beta-hydroxylase (ASPH) were validated. Coiled-coil domain containing protein 47 (CCDC47) ranked as a high confidence SPCA2C-interactor which was confirmed through immunoprecipitation and co-localization with SPCA2C. CCDC47 interactions with SPCA2C, STIM1 and Orai1 were maintained following deletion of the CCDC47 luminal and cytosolic domains while deletion of only the coiled-coil domain altered CCDC47 localization and decreased interactions with STIM1 and Orai1. Overall, this study defines several novel protein interactions for SPCA2C and suggests it may be involved in affecting CCDC47, STIM1 and Orai1 function.
Deletion of exons 45 to 55 in theDMDgene: from the therapeutic perspective to thein vitromodel
Authors: Poyatos-García Javier , Soblechero-Martín Patricia , Liquori Alessandro , López-Martínez Andrea , González-Romero Elisa , Vázquez-Manrique Rafael P. , Muelas Nuria , García-García Gema , Ohana Jessica , Arechavala-Gomeza Virginia , Vílchez Juan J. 
Published: September 2023

ABSTRACTGene editing therapies in development for correcting out-of-frameDMDmutations in Duchenne muscular dystrophy aim to replicate benign spontaneous deletions. Deletion of 45–55DMDexons (del45–55) was described in asymptomatic subjects, but recently serious skeletal and cardiac complications have been reported. Uncovering why a single mutation like del45–55 is able to induce diverse phenotypes and grades of severity may impact the strategies of emerging therapies. Cellular models are essential for this purpose, but their availability is compromised by scarce muscle biopsies. Here, we have introduced through CRISPR-Cas9 edition, a del45–55 mimicking the intronic breakpoints harboured by a subset of patients of this form of dystrophinopathy, into a Duchenne patient’s cell line. Dystrophin expression was restored in edited myoblasts and the myogenic defects were ameliorated. Besides confirming the potential of CRISPR-Cas9 to create tailored mutations as a useful approach to generatein vitromodels, we also generated an immortalized myoblast line derived from a patient with a specific del45–55. Overall, we provide helpful resources to deepen into unknown factors responsible for DMD-pathophysiology.SUMMARY STATEMENTWe restored dystrophin expression in a DMD culture by replicating the exact deletion in exons 45-55 harboured by mild patients, testing this therapeutic approach, and creating a new cell model.
Spatiotemporal Proteomics Deciphers Functional Selectivity of EGFR ligands
Authors: Eguchi Akihiro , Emdal Kristina B. , Ye Zilu , Guzmán Ulises H. , Olsen Jesper V. 
Published: September 2023

SummaryThe epidermal growth factor receptor (EGFR) induces different signaling outputs depending on ligand identity and biological context. This phenomenon is known as functional selectivity, but the underlying molecular mechanisms remain elusive. Here, we investigated this on a global scale and time-resolved by high-throughput multilayered proteomics integrating dynamic changes in the EGFR interaction network by proximity biotinylation using EGFR- TurboID, phosphoproteome, and proteome in response to stimulation with the six highest-affinity EGFR ligands. We obtained comprehensive temporal profiles of protein recruitment and phosphosite changes pinpointing signaling proteins differentially regulated by the six ligands with key impact on EGFR endocytic fate, e.g. degradation or recycling. Specifically, the Epsin family protein, Clint1 was identified to control the endocytic trafficking of EGFR towards degradation. Moreover, we characterized the protein interaction selectivity of EGFR C-terminally phosphorylated tyrosine residues using a panel of tyrosine mutated constructs showing STAT5 specificity for EGFR Y1173. These data provide a comprehensive resource deciphering functional selectivity of EGFR signaling to support discovery of novel drug targets.
Understanding consumers' intentions to use drone food delivery services: a perspective of the theory of consumption values
Authors: Koay Kian Yeik , Leong Mei Kei 
Published: September 2023

PurposeThe purpose of this study is to examine the factors influencing consumers' intentions to use drone food delivery services from the perspective of the theory of consumption values (TCV).Design/methodology/approachData collection involves the utilisation of self-administered questionnaires. Subsequently, 305 data were gathered from Malaysian consumers and subjected to analysis through partial least squares structural equation modelling (PLS-SEM).FindingsThis study demonstrated that functional, social, emotional and epistemic values, as well as personal innovativeness, can strongly predict intentions. However, neither the conditional value nor environmental concerns were significant predictors of intentions.Originality/valueThe study is the first of its kind to use the TCV from the perspective of a developing country to understand consumers' intentions to use drone food delivery services.
Years of education and research driven in sustainable architecture: Where do we stand and where do we go?
Authors: Sheta Wael 
Published: September 2023

PurposeThe purpose of this study is to give an informative map of sustainable architectural education by focusing on publishing trends, prominent publications, prolific contributors, research challenges and future research prospects. As a consequence, an efficient framework for collecting significant knowledge and identifying prevalent topics in sustainable architectural education towards more sustainable environments at the urban and building scales may be provided.Design/methodology/approachThe methodology adopted in this study is based on examining the subjects of many consecutive rounds of the Passive and Low Energy Architecture (PLEA) conference, with an emphasis on the most recent five rounds. The PLEA's official website served as the main source for gathering all proceedings. Earlier rounds from 2016 to 2020, which cover a time span of five years, were utilized to analyze patterns during that time period. The rationale for selecting this time period was the limited availability of data required to observe the trends, area of interest and emerging themes in these fields that could be analyzed qualitatively.FindingsThe findings show that the following drive themes emerged around education and research-driven sustainable architecture: emerging design as a core idea; concentration on the way of delivering and developing education; constructing and shaping the building; assessing current practices; acquiring and recruiting knowledge and new concepts; reporting on the current condition; portraying the target audience and ensuring the long-term viability of the architectural educational process. This insight provides academics and professionals a greater grasp of the state of the art, allowing them to direct their research toward developing concerns in education and research-driven sustainable design.Originality/valueThe study results provide an effective framework for collecting relevant content and identifying prominent topics in sustainable, passive and passive low-energy architecture for the creation of more sustainable urban and building environments. Furthermore, this qualitative and exploratory study may serve as a framework for those researching, creating and verifying different research approaches in education and research-driven sustainable architecture.
Busy CEOs and audit fees: evidence from Indonesia
Authors: Harymawan Iman , Putri Fiona Vista , Ratri Melinda Cahyaning , Nasih Mohammad 
Published: September 2023

Purpose
A company needs to use auditing procedures to ensure the reliability of financial statements while also providing transparency to stakeholders. The extent of risk associated with the company depends on the directors’ involvement in its daily operations. This paper aims to study the relationship between busy chief executive officers (CEOs) and audit fees.

Design/methodology/approach
This study uses 1,037 data samples from companies listed on the Indonesia Stock Exchange from 2010 until 2018. It adopts the ordinary least squares method to test the hypothesis. Furthermore, this study performs robustness tests, such as propensity score matching (PSM) and Heckman’s two-stage least square tests (Heckman, 1979), to address the endogeneity issues.

Findings
This study finds that the appearance of a busy CEO in a company will significantly increase the audit fee. It also concludes that a long tenure of a busy CEO will substantially weaken the positive relationship between the CEO and the audit fee. However, this study discovers that, in a company with a busy CEO, a monitoring mechanism through the independent commissioner and risk management committee will only help to maximize the firm’s practical risk evaluation a little. This result is robust because the PSM and Heckman tests display consistent results, so it is free from endogeneity issues.

Practical implications
This study is valuable for theoretical and practical development in Indonesia. Due to the minimum regulation about multiple positions on boards in Indonesia, the shareholders must be aware of the need to choose a board with more skill and commitment to improve the position of the company. This result also warns the C-level of the company to pay more attention to its risk-monitoring process to make it more effective and efficient.

Originality/value
Indonesia is one of the countries that have implemented the two-tier governance system. With the minimum regulation about multiple directorships in Indonesia, this study offers new insights into how a busy CEO will be related to the audit outcomes.
An intellectual design case of compressor airfoils based on reinforcement learning
Authors: Xu Xiaohan , Huang Xudong , Zhang Ke , Zhou Ming 
Published: September 2023

PurposeIn general, the existing compressor design methods require abundant knowledge and inspiration. The purpose of this study is to identify an intellectual design optimization method that enables a machine to learn how to design it.Design/methodology/approachThe airfoil design process was solved using the reinforcement learning (RL) method. An intellectual method based on a modified deep deterministic policy gradient (DDPG) algorithm was implemented. The new method was applied to agents to learn the design policy under dynamic constraints. The agents explored the design space with the help of a surrogate model and airfoil parameterization.FindingsThe agents successfully learned to design the airfoils. The loss coefficients of a controlled diffusion airfoil improved by 1.25% and 3.23% in the two- and four-dimensional design spaces, respectively. The agents successfully learned to design under various constraints. Additionally, the modified DDPG method was compared with a genetic algorithm optimizer, verifying that the former was one to two orders of magnitude faster in policy searching. The NACA65 airfoil was redesigned to verify the generalization.Originality/valueIt is feasible to consider the compressor design as an RL problem. Trained agents can determine and record the design policy and adapt it to different initiations and dynamic constraints. More intelligence is demonstrated than when traditional optimization methods are used. This methodology represents a new, small step toward the intelligent design of compressors.