bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders
Authors: Cheng Xiaopo , Caruso Christina , Lam Wilbur A. , Graham Michael D. 
Published: May 2023

Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily observed, in conditions such as sickle cell disease and iron deficiency, RBC disorders can also be associated with vascular dysfunction. The mechanisms of vasculopathy in those diseases remain unclear and scant research has explored whether biophysical alterations of RBCs can directly affect vascular function. Here we hypothesize that the purely physical interactions between aberrant RBCs and endothelial cells, due to the margination of stiff aberrant RBCs, play a key role in this phenomenon for a range of disorders. This hypothesis is tested by direct simulations of a cellular scale computational model of blood flow in sickle cell disease, iron deficiency anemia, COVID-19, and spherocytosis. We characterize cell distributions for normal and aberrant RBC mixtures in straight and curved tubes, the latter to address issues of geometric complexity that arise in the microcirculation. In all cases aberrant RBCs strongly localize near the vessel walls (margination) due to contrasts in cell size, shape, and deformability from the normal cells. In the curved channel, the distribution of marginated cells is very heterogeneous, indicating a key role for vascular geometry. Finally, we characterize the shear stresses on the vessel walls; consistent with our hypothesis, the marginated aberrant cells generate large transient stress fluctuations due to the high velocity gradients induced by their near-wall motions. The anomalous stress fluctuations experienced by endothelial cells may be responsible for the observed vascular inflammation.Significance StatementA common and potentially life-threatening complication of blood cell disorders is inflammation and dysfunction of the vascular wall, for reasons that remain unclear. To address this issue, we explore a purely biophysical hypothesis involving red blood cells using detailed computational simulations. Our results show that red blood cells that are pathologically altered in cell shape, size, and stiffness, which occurs in various blood disorders, strongly marginate, residing primarily in the cell-free layer near blood vessel walls, generating large shear stress fluctuations at the vessel wall that may be responsible for endothelial damage and inflammation.
Presenilin homologues influence substrate binding and processing by γ-secretase: a molecular simulation study
Authors: Eccles Melissa K , Groth David , Verdile Giuseppe , Agostino Mark 
Published: May 2023

ABSTRACTPresenilin homologues in the γ-secretase complex play a pivotal role in substrate binding and processing, impacting β-amyloid (Aβ) peptide generation in Alzheimer’s disease. We conducted a molecular simulation study to determine substrate preferences between presenilin-1 (PS1) and presenilin-2 (PS2) γ-secretase enzymes for amyloid precursor protein (APP) and Notch1 processing. Using homology modelling, we generated PS1- and PS2-γ-secretase models bound to substrates in the Aβ40 and Aβ42 generation pathways and Notch1 S3 and S4 cleavage site substrates. Metadynamics simulations and binding free energy calculations were used to explore conformational ensembles and substrate preferences. PS2-γ-secretase exhibited increased conformational flexibility and preferential binding energy for initiating the Aβ42 pathway compared to PS1-γ-secretase. Additionally, Notch1 exhibits a preference for binding to PS2-γ-secretase over PS1-γ-secretase. This study provides valuable insights into the conformational dynamics of γ-secretase bound to different substrates within a cleavage pathway, improving our understanding of substrate processivity. The findings highlight the importance of considering both PS1- and PS2-γ-secretase in structure-based drug design efforts, with implications for stabilizing or destabilizing specific states during APP processing.
The FIGNL1-FIRRM complex is required to complete meiotic recombination in the mouse and prevents massive DNA damage-independent RAD51 and DMC1 loading
Authors: Zainu Akbar , Dupaigne Pauline , Bouchouika Soumya , Cau Julien , Clément Julie A. J. , Auffret Pauline , Ropars Virginie , Charbonnier Jean-Baptiste , de Massy Bernard , Mercier Raphael , Kumar Rajeev , Baudat Frédéric 
Published: May 2023

AbstractDuring meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulate RAD51 in human cells. However, FIGNL1’s role during meiotic recombination in mammals remains unknown. Here, we deciphered the meiotic functions of FIGNL1 and FIGNL1 Interacting Regulator of Recombination and Mitosis (FIRRM) using male germline-specific conditional knock-out (cKO) mouse models. Both FIGNL1 and FIRRM are required for completing meiotic prophase in mouse spermatocytes. Despite efficient recruitment of DMC1 on ssDNA at meiotic DSB hotspots, the formation of late recombination intermediates is defective inFirrmcKO andFignl1cKO spermatocytes. Moreover, the FIGNL1-FIRRM complex limits RAD51 and DMC1 accumulation on intact chromatin, independently from the formation of SPO11-catalyzed DSBs. Purified human FIGNL1ΔN alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasionin vitro. Thus, this complex might regulate RAD51 and DMC1 association at sites of meiotic DSBs to promote proficient strand invasion and processing of recombination intermediates.
TREM2 promotes glioma progression and angiogenesis mediated by microglia/brain macrophages
Authors: Chen Xuezhen , Zhao Yue , Huang Yimin , Zhu Kaichuan , Zeng Fan , Zhao Junyi , Zhang Huaqiu , Zhu Xinzhou , Kettenmann Helmut , Xiang Xianyuan 
Published: May 2023

AbstractTREM2, a myeloid cell-specific signaling molecule, controls essential functions of microglia and impacts on the pathogenesis of Alzheimer’s disease and other neurodegenerative disorders. TREM2 is also highly expressed in tumor-associated macrophages and plays detrimental roles in an experimental mouse sarcoma model. Here we studied whether TREM2 influences glioma progression. We found a sex- dependent effect of TREM2: the glioma volume is significantly attenuated in TREM2- deficient male but not female mice injected with GL261-EGFP glioma cells. The accumulation of glioma-associated microglia/macrophages (GAMs) and vascularization is reduced in male TREM2-deficient mice. A transcriptomic analysis of glioma tissue revealed that TREM2 deficiency suppresses angiogenic genes and MHC clusters. In an organotypic slice model devoid of functional vascularization, the tumor size was not affected by TREM2-deficiency. In human resection samples from glioblastoma, TREM2 is upregulated in GAMs. Based on the TCGA and CGGA databases, the TREM2 expression levels are negatively correlated with survival. Thus, the TREM2-dependent crosstalk between GAMs and the vasculature formation promotes glioma growth.Graphic abstractTREM2-dependent crosstalk between glioma-associated microglia/macrophages and the vasculature formation promotes glioma growth in male glioma mouse model. Created with BioRender.com
Pre-saccadic Preview Shapes Post-Saccadic Processing More Where Perception is Poor
Authors: Liu Xiaoyi , Melcher David , Carrasco Marisa , Hanning Nina M. 
Published: May 2023

AbstractThe pre-saccadic preview of a peripheral target enhances the efficiency of its post-saccadic processing, termed the extrafoveal preview effect. Peripheral visual performance –and thus the quality of the preview– varies around the visual field, even at iso-eccentric locations: it is better along the horizontal than vertical meridian and along the lower than upper vertical meridian. To investigate whether these polar angle asymmetries influence the preview effect, we asked human participants (to preview four tilted gratings at the cardinals, until a central cue indicated to which one to saccade. During the saccade, the target orientation either remained or slightly changed (valid/invalid preview). After saccade landing, participants discriminated the orientation of the (briefly presented) second grating. Stimulus contrast was titrated with adaptive staircases to assess visual performance. Expectedly, valid previews increased participants’ post-saccadic contrast sensitivity. This preview benefit, however, was inversely related to polar angle perceptual asymmetries; largest at the upper, and smallest at the horizontal meridian. This finding reveals that the visual system compensates for peripheral asymmetries when integrating information across saccades, by selectively assigning higher weights to the less-well perceived preview information. Our study supports the recent line of evidence showing that perceptual dynamics around saccades vary with eye movement direction.Significance StatementWe constantly make saccadic eye movements to bring relevant visual information into the fovea, which has the highest acuity. Before each saccade, we use “previewed” peripheral information to support our post-saccadic vision. Our sensitivity varies around the visual field –at the same eccentricity it is best along the horizontal meridian and worst at the upper vertical meridian. An optimal visual system should rely more on previewed information with higher precision. Our study reveals the opposite: peripheral preview shapes subsequent post-saccadic foveal processing more at locations where peripheral vision is worse. This finding implies that the human visual system compensates for sensitivity differences around the visual field when integrating information across eye movements.
Deletion of competence genes represses expression of genes associated with anaerobic respiration/metabolism inAggregatibacter actinomycetemcomitans
Authors: Vahvelainen Nelli , Kovesjoki Laura , Maula Terhi , Ihalin Riikka 
Published: May 2023

AbstractBiofilm formation contributes to the virulence of various pathogens, as the extracellular polymer matrix provides protection against the host immune defense and antimicrobial drugs. Biofilm- associated diseases often become chronic and recurring. The periodontal pathogenAggregatibacter actinomycetemcomitans, which resides in a multispecies biofilm in the subgingival pocket, produces multiple virulence factors that can contribute to disease progression. Certain strains of the species are naturally competent, which allows uptake of extracellular DNA that can be incorporated into the bacterial genome or used as a nutrient. Earlier studies indicated that bacterial interleukin receptor I (BilRI) and the type IV pilus subunit PilA protein are needed for efficient transformation inA. actinomycetemcomitans. In this study, we show that the outer membrane secretin HofQ is required for natural competence, as deletion of thehofQgene results in a nontransformable strain. Furthermore, we studied the gene expression profiles of three single-gene mutants of the naturally competentA. actinomycetemcomitansstrain D7S, all of which have decreased transformation efficiency compared to the wild-type strain. Additionally, asA. actinomycetemcomitanscan bind to and internalize interleukin (IL)-1β, the effect of IL-1β on bacterial gene expression was also studied. However, in our experimental setup, the addition of IL-1β did not change gene expression in theA. actinomycetemcomitansstrains used. The mutant strain lacking thebilRIgene exhibited a gene expression pattern similar to that of the wild-type strain. However, deletion ofhofQorpilAresulted in altered gene expression. Interestingly, genes associated with anaerobic growth, biofilm formation, and virulence were downregulated in the ΔhofQand ΔpilAdeletion mutants, which could indicate a decreased colonization ability and reduced virulence.
Do satisfied customers recommend restaurants? The moderating effect of engagement on social networks on the relationship between satisfaction and eWOM
Authors: Chinelato Flavia Braga , Oliveira Alessandro Silva de , Souki Gustavo Quiroga 
Published: May 2023

PurposeAcademics and managers scour to understand which perceived quality factors are paramount to consumers during their restaurant experiences and how they influence their emotions, satisfaction, propensity to loyalty and electronic word-of-mouth (eWOM). However, previous studies are divergent regarding the impacts of satisfaction on eWOM. This survey aims to (a) investigate the impacts of perceived quality by restaurant consumers on positive emotions, negative emotions and satisfaction; (b) verify the impacts of satisfaction on the propensity to loyalty and eWOM; (c) test whether the consumers’ behavioural engagement in the SNS (CBE-SNS) moderates the relationship between satisfaction and eWOM.Design/methodology/approachThis survey included 416 university students in Peru who completed an electronic form about their experiences at à la carte restaurants. PLS-SEM tested the hypothetical model based on S-O-R Theory (Mehrabian and Russell, 1974).FindingsThe perceived quality by consumers regarding their restaurant experiences positively impacts satisfaction and positive emotions and negatively affects negative emotions. Satisfaction strongly influences the propensity to loyalty but weakly the eWOM. The CBE-SNS moderates the intensity of the relationship between satisfaction and eWOM.Originality/valueThis study is the first to concomitantly test the relationships between perceived quality, positive and negative emotions, satisfaction, the propensity to loyalty, e-WOM and CBE-SNS. Consumer engagement moderates the relationship between satisfaction and eWOM. Accordingly, to stimulate positive eWOM, restaurants must provide their customers with experiences with high perceived quality, impacting their satisfaction, emotions and propensity for loyalty, and developing strategies to increase CBE-SNS.
Does polychronicity among sales employees develop B2B service recovery? A dual assessment through ambidextrous leadership
Authors: Ahmad Bilal , Yuan Jingbo , Akhtar Naeem , Waheed Abdul 
Published: May 2023

PurposeThis research explores the determinants and consequences of salesperson polychronicity in a business-to-business (B2B) sales environment. Additionally, the study examined the link between the antecedents and consequences of salesperson polychronicity using resistance to change (RC) and manager trust in salesperson (MT) as moderators.Design/methodology/approachA conceptual framework was developed by testing eight hypotheses based on data collected from 378 salesperson-manager dyads.FindingsThe authors find that opening leader behavior is positively associated with salesperson polychronicity, while closing leader behavior negatively influences salesperson polychronicity. In addition, salesperson polychronicity positively affects service recovery performance and customer-directed organizational citizen behaviors (OCB). Finally, the RC and MT significantly and positively moderate the linkage between the antecedents and consequences of salesperson polychronicity.Originality/valueThis study is original because this is the first study to address polychronicity as an individual trait in a B2B environment where multitasking behavior is of paramount importance.
Municipal facilities managers as strategists
Authors: Gluch Pernilla , Svensson Ingrid , Bröchner Jan 
Published: May 2023

Purpose
This study aims to investigate practitioners’ perceptions of strategic work in municipal facilities management: how public facilities management is changing, what is included in strategic public facilities management and who leads the strategic work.

Design/methodology/approach
A literature review begins with mainstream studies of strategy management, ultimately concentrating on municipal facilities management. Findings are based on a 2020/2021 questionnaire targeting 356 practitioners in municipal facilities management across Sweden (50% response rate). The statistical treatment includes factor analysis.

Findings
Most respondents indicated changed ways of managing facilities in the past five years; most reported that they were in an organization with an explicit goal of working more strategically. Respondents associated strategic facilities management with governance, facilities, sustainability, technology change and communication. Frequently, it was the management team of the facilities management department that led strategic work.

Research limitations/implications
Research into municipal facilities management is dominated by studies in Northern Europe, and more studies from other regions are needed. How strategies and work roles evolve in parallel appears to be a fruitful direction of further research.

Practical implications
Facilities managers need stronger competences and more resources to engage in strategic facilities management. Findings indicate a need to integrate sustainability aspects better into long-term strategic work.

Social implications
More strategic municipal facilities management is of obvious social value.

Originality/value
This is the first study of practitioner perceptions of work on strategic facilities management in municipalities.
Examining the trade-led Kuznets hypothesis for emerging economies: a multivariate framework
Authors: Jain Neha , Mohapatra Geetilaxmi 
Published: May 2023

PurposeThe present study aims to investigate the non-linear relationship between trade and income inequality to address goal 10 of sustainable development goals (SDGs) using the Kuznets Curve (KC) framework for major emerging countries during 1991–2020.Design/methodology/approachFor this purpose, recent econometric techniques, such as Common Correlated Effect (CCE) and Dynamic Common Correlated Effect (DCCE) estimators have been employed to deal with the cross-section dependence (CD) that arises in panel data, while the robustness of the study is checked through Driscoll–Kraay standard errors method.FindingsThe empirical results of the study confirm the existence of inverted “U-shaped” relationship between trade and income inequality suggesting evidence for the trade-led KC in the panel of emerging countries. Along with the non-linear model, the threshold value is estimated to be between 3.5 and 4% of gross domestic product (GDP).Research limitations/implicationsThe authors' findings support that trade contributes significantly toward reducing income inequality and helps in achieving goal 10 of SDGs. Hence, trade policies appear to be more egalitarian. The results widen the scope for further research and provide insights for regulators and policymakers in modeling trade policies and changing the status quo trade policy framework accordingly.Originality/valueThe present study is a pioneering attempt to examine the non-linear relationship between trade and income inequality under the KC framework in light of the Agenda 2030 for sustainable development. The study also considers other explanatory factors that have an impact on income inequality. Furthermore, the study considers other explanatory factors that have an impact on income inequality, and the attempt to estimate the threshold value for the trade-led KC is novel and interesting.
Development of cultural agility competencies through global mobility
Authors: Caligiuri Paula M. 
Published: May 2023

PurposeThis paper aims to understand how these competencies gained will help human resource (HR) leaders become more strategic about when and how to use global mobility for talent development.Design/methodology/approachIn this paper, the author defines the construct of cultural agility and describes the theoretical mechanisms through which employees can gain cultural agility through culturally novel situations such as global mobility. Cultural agility enables individuals to work comfortably and effectively with people from different cultures and in situations of cultural novelty. People with cultural agility have task-management competencies (cultural minimization, adaptation and integration), self-management competencies (tolerance of ambiguity, resilience, curiosity) and relationship-management competencies (humility, relationship building and perspective taking).FindingsThis study aims at focusing on the development of cultural agility, this paper focuses on four cascading features of a culturally novel experience that can help individuals gain this competence: (1) the level of cultural novelty in the experience, (2) the readiness of an individual for that level of cultural novelty, (3) the individual's level of awareness of the cultural norms and values inherent in the culturally novel experience and (4) the level of social support offered to that individual to learn how to understand and respond in that experience.Originality/valueEach feature is discussed, concluding with the implications for future research and practitioners in global mobility and talent development.
Traveling with special needs: investigating constraints and negotiation strategies for engaging in tourism activities
Authors: Devile Eugenia Lima , Eusébio Celeste , Moura Andreia 
Published: May 2023

PurposeThe aim of this study is to identify the travel constraints of people with special needs (PwSN) and the strategies used to overcome them. The article also intends to analyze the differences in travel constraints and negotiation strategies according to the type of disability and/or special need.Design/methodology/approachA qualitative study was conducted in which a sample of PwSN (people with disabilities – mobility, sensory and cognitive – seniors and people with food allergies) were interviewed in depth.FindingsPwSN face a wide range of constraints when engaging in tourism activities. These constraints are very diverse and influence people with different intensity and have to be overcome using different negotiation strategies. However, differences in the constraints were observed according to the type of special needs.Practical implicationsOne of the most significant practical implications of this research is the need for raising awareness regarding human diversity among tourism stakeholders. It is critical to link sectoral policies that are reflected in the social and business reality, creating public–private partnerships to raise the sharing of knowledge, equipment and services. By addressing the constraints that prevent PwSN from traveling, the tourism sector can create more opportunities for them to participate in social activities, improving their quality of life and contributing to a more sustainable and inclusive industry.Originality/valueTraveling can present significant challenges for people with special needs, which affect the quality of their tourism experience. Despite growing academic attention to this issue in recent years, research in this field has primarily focused on specific aspects of disability. This study seeks not only to identify the barriers to travel faced by people with different special needs but also to explore the negotiation strategies used to overcome these barriers and the differences according to the type of special need.