bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical Strain Activates Planar Cell Polarity Signaling to Coordinate Vascular Cell Dynamics
Authors: Golbach Lieke , Saha Tanumoy , Odenthal-Schnittler Maria , Lücking Jenny , Velic Ana , Akmeric Emir Bora , Bornhorst Dorothee , Popp Oliver , Mertins Philipp , Gunawan Felix , Gerhardt Holger , Macek Boris , Trappmann Britta , Schnittler Hans J. , Galic Milos , Matis Maja 
Published: June 2024

SUMMARYMechanical stimuli, particularly laminar blood flow, play a crucial role in shaping the vascular system. Changes in the rate of blood flow manifest in altered shear stress, which activates signaling cascades that drive vascular remodeling. Consistently, dysregulation of the endothelial response to fluid shear forces and aberrant flow patterns both lead to pathological conditions, including impaired blood vessel development and atherosclerosis. Despite its importance, the mechanisms driving the coordinated cell behavior underlying vascular remodeling are not fully understood. Combining classical cell biological approaches with advanced image analysis, mathematical modeling, biomimetic strategies, and in vivo studies, we identify the planar cell polarity (PCP) protein Vangl1 as an enforcer of flow-dependent cell dynamics in the vascular system. We demonstrate that shear stress triggers the relocation of Vangl1 from an internal reservoir to the plasma membrane at the initiation of cell remodeling. Membrane enrichment of Vangl1 is mediated by a Coronin1C-dependent shift in the equilibrium between endo- and exocytosis and results in the spatial reorganization of another essential PCP protein, Frizzled6 (Fzd6). The resulting mutual exclusion of the core PCP proteins Fzd6 and Vangl1 augments differential junctional and cytoskeletal dynamics along the flow axis. Loss of Vangl1 limits the ability of endothelial cells to respond to shear forces in a coordinated fashion, resulting in irregular cell alignment along the flow direction and erroneous vessel sprouting. Together, these studies introduce core PCP signaling as a determinant of collective cell dynamics and organization of the vascular system.
HOCl Forms LipidN-Chloramines in Cell Membranes of Bacteria and Immune Cells
Authors: Knoke Lisa R. , Abad Herrera Sara , Heinrich Sascha , Lupilov Natalie , Bandow Julia E. , Günther Pomorski Thomas 
Published: June 2024

AbstractNeutrophils orchestrate a coordinated attack on bacteria, combining phagocytosis with a potent cocktail of oxidants, including the highly toxic hypochlorous acid (HOCl), renowned for its deleterious effects on proteins. Here, we examined the occurrence of lipidN-chloraminesin vivo, their biological activity and neutralization. Using a chemical probe forN-chloramines, we demonstrate their formation in the membranes of bacteria and monocytic cells exposed to physiologically relevant concentrations of HOCl.N-chlorinated model membranes composed of phosphatidylethanolamine, the major membrane lipid inEscherichia coliand an important component of eukaryotic membranes, exhibited oxidative activity towards the redox-sensitive protein roGFP2, suggesting a role for lipidN-chloramines in protein oxidation. Conversely, the cellular antioxidant glutathione neutralized lipidN-chloramines by removing the chlorine moiety. We propose that lipidN-chloramines, like proteinN-chloramines, are involved in inflammation and accelerate the host immune response.
The PIN1-p38-CtIP signaling axis protects stalled replication forks from deleterious degradation
Authors: Vivalda Francesca , Gatti Marco , Manfredi Letizia , Dogan Hülya , Porro Antonio , Collotta Giulio , Ceppi Ilaria , von Aesch Christine , van Ackeren Vanessa , Wild Sebastian , Steger Martin , Canovas Begoña , Cubillos-Rojas Monica , Riera Antoni , Cejka Petr , Nebreda Angel R. , Dibitetto Diego , Rottenberg Sven , Sartori Alessandro A. 
Published: June 2024

ABSTRACTHuman CtIP plays a critical role in homologous recombination (HR) by promoting the resection of DNA double-strand breaks. Moreover, CtIP maintains genome stability through protecting stalled replication forks from nucleolytic degradation. However, the upstream signaling mechanisms governing the molecular switch between these two CtIP-dependent processes remain largely elusive. Here, we show that phosphorylation of CtIP by the p38α stress kinase and subsequent PIN1-mediated CtIPcis-to-transisomerization is required for fork stabilization but dispensable for HR. We found that stalled forks are degraded in cells expressing non-phosphorylatable CtIP or lacking PIN1-p38α activity, while expression of a CtIPtrans-locked mutant overcomes the requirement for PIN1-p38α in fork protection. We further reveal thatBrca1-deficient mammary tumor cells that have acquired PARPi resistance regain chemosensitivity after PIN1 or p38α inhibition. Collectively, our findings identify the PIN1-p38-CtIP signaling pathway as a critical regulator of replication fork integrity.
Piezo1 is a mechanosensor of soft matrix viscoelasticity
Authors: Oliva Mariana A. G. , Ciccone Giuseppe , Luo Jiajun , Voigt Jonah L. , Romani Patrizia , Dobre Oana , Dupont Sirio , Vassalli Massimo , Salmeron-Sanchez Manuel 
Published: June 2024

AbstractMechanosensitive ion channels have emerged as fundamental proteins in sensing extracellular matrix (ECM) mechanics. Among those, Piezo1 has been proposed as a key mechanosensor in cells. However, whether and how Piezo1 senses time-dependent ECM mechanical properties (i.e., viscoelasticity) remains unknown. To address this question, we combined an immortalised mesenchymal stem cell (MSC) line with adjustable Piezo1 expression with soft (400 Pa) and stiff (25 kPa) viscoelastic hydrogels with independently tuneable Young’s modulus and stress relaxation. We demonstrate that Piezo1 is a mechanosensor of viscoelasticity in soft ECMs, consistent with the molecular clutch model. By performing RNA sequencing (RNA-seq), we identified the transcriptomic phenotype of MSCs response to matrix viscoelasticity and Piezo1 activity, highlighting gene signatures that drive MSCs mechanobiology in soft and stiff viscoelastic hydrogels.
Unraveling an unknown diversity of archaeal and bacterial tetraether membrane lipid producers in a euxinic marine system
Authors: Boukhchtaber Dina Castillo , von Meijenfeldt F. A. Bastiaan , Canavesi Diana X. Sahonero , Dorhout Denise , Bale Nicole J. , Hopmans Ellen C. , Villanueva Laura 
Published: June 2024

SummaryBacterial membrane lipids have been traditionally defined as fatty acids (FAs) bilayers linked through ester bonds, while those of Archaea as ether-linked isoprenoids forming bilayers or monolayers of membrane spanning lipids (MSLs) known as isoprenoidal glycerol dialkyl glycerol tetraethers (isoGDGTs). This paradigm has been challenged with the discovery of branched GDGTs (brGDGTs), membrane spanning ether-bound branched alkyl FAs, that are of bacterial origin but whose specific producers in the environment are often unknown. The limited number of available microbial cultures restricts the knowledge of the biological sources of membrane lipids, which in turn limits their potential applicability as biomarkers. To address this limitation, we detected membrane lipids in the Black Sea using high resolution accurate mass/mass spectrometry and inferred their potential producers by targeting lipid biosynthetic pathways encoded on the metagenome, in metagenome-assembled genomes and unbinned scaffolds. We also detected brGDGTs and overly branched GDGTs in the suboxic and euxinic waters, which are potentially attributed, to members of the Planctomycetota, Cloacimonadota, Desulfobacterota, Chloroflexota, Actinobacteria and Myxococcota—all anaerobic microorganisms. These results open a new chapter in the use of specific brGDGTs as biomarkers of anoxic conditions in marine settings and of the role of these membrane lipids in microbial adaptation.
Blocking HXA3-mediated neutrophil elastase release duringS. pneumoniaelung infection limits pulmonary epithelial barrier disruption and bacteremia
Authors: Xu Shuying , Tan Shumin , Romanos Patricia , Reedy Jennifer L. , Zhang Yihan , Mansour Michael K. , Vyas Jatin M. , Mecsas Joan , Mou Hongmei , Leong John M. 
Published: June 2024

AbstractStreptococcus pneumoniae(Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant three-fold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The majorSpvirulence factor, pneumolysin (PLY), triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination duringSplung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface (ALI) cultures that lack this enzyme to show that HXA3methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitantSpbarrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant fMLP did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased release of neutrophil elastase (NE) fromSp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3promotes barrier disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.ImportanceStreptococcus pneumoniae(Sp), a leading cause of pneumonia, can spread from the lung into the bloodstream to cause systemic disease. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that limit pathologic host immune responses toSp. Excessive polymorphonuclear leukocyte (PMN) infiltration intoSp-infected airways promotes systemic disease. Using stem cell-derived respiratory cultures that reflectbona fidelung epithelium, we identified the eicosanoid hepoxilin A3 as a critical pulmonary PMN chemoattractant that is sufficient to drive PMN-mediated epithelial damage by inducing the release of neutrophil elastase. Inhibition of the release or activity of this protease in mice limited epithelial barrier disruption and bacterial dissemination, suggesting a new host-directed treatment forSplung infection.
Realizing Mechanical Frustration at the Nanoscale Using DNA Origami
Authors: Madhvacharyula Anirudh S. , Li Ruixin , Swett Alexander A. , Du Yancheng , Simmel Friedrich C. , Choi Jong Hyun 
Published: June 2024

ABSTRACTStructural designs inspired by physical and biological systems have been previously utilized to develop advanced mechanical metamaterials. These are based on the clever geometric arrangement of their building blocks, resulting in enhanced mechanical properties such as shape morphing and auxetic behavior. Until now, the benefits from such designs have yet to be leveraged at the nanoscale. Here, we use the DNA origami method to realize a nanoscale metastructure exhibiting mechanical frustration, the mechanical counterpart of the well-known phenomenon of magnetic frustration. We show that this DNA metastructure can be precisely controlled to adopt either frustrated or non-frustrated mechanical states, each characterized by a distinct free energy profile. Switching among the states is achieved by engineering reconfigurable struts into the structure. Actuation of the struts causes a global deformation of the metastructures. In the non-frustrated state, strain can be distributed homogeneously throughout the structure, while in the frustrated state, strain is concentrated at a specific location. Molecular dynamics simulations reconcile the contrasting behaviors of the two modes and provide detailed insights into the mechanics. Our work demonstrates how combining programmable DNA self-assembly with mechanical design principles can overcome engineering limitations encountered at the macroscale, enabling the development of dynamic, deformable nanostructures with tunable responses. These may lay the foundation for mechanical energy storage elements, nanomechanical computation, and allosteric mechanisms in DNA-based nanomachinery.
Impediments to building information modelling-enabled construction waste management in Nigeria
Authors: Eze Emmanuel Chidiebere , Sofolahan Onyinye , Uzoma Clementina Nneji , Ameyaw Ernest Effah , Omoboye Olayinka 
Published: June 2024

PurposeBuilding Information modelling (BIM) has the potential to significantly minimise the quantity of construction waste (CW), but its adoption is low in construction waste management (CWM). This study examined the factors impeding the adoption of BIM in CWM efforts at the design and precontract stages from the perspective of construction stakeholders in Nigeria.Design/methodology/approachThe study was informed by a post-positivism philosophical stance, which involved using the structured questionnaire as a quantitative research design tool for data collection via snowball sampling technique. The data garnered from construction experts were analysed using Cronbach’s alpha test, normalities test, Frequency, Percentage, Kendall’s coefficient of concordance and Chi-square tests, Analysis of variance (ANOVA), and exploratory factors analysis (EFA).FindingsThe study concluded that the awareness of BIM potential for CWM is high, but the adoption in waste management (WM) is low. The factor analysis reduced the twenty assessed factors into four key clusters of impediments to BIM adoption in CWM: (1) knowledge and resistance barriers, (2) support and interest barriers, (3) interoperability and experts' factors, and (4) economic barriers. These factors are critical impediments to BIM-enabled CWM at the design and precontract stage, and there was no significant statistical difference in their rating by the construction stakeholders in Nigeria.Originality/valueStudies on the impediments to BIM adoption in CWM efforts, primarily at the design and pre-contract stages in emerging countries are scarce. This sought to fill this literature gap by establishing the critical impediments that should be overcome to improve BIM use in CWM.
So, you think you are a leader? A qualitative study to understand patterns of presentation and symmetry among dimensions of leader identity
Authors: McCombs Kate , Williams Ethlyn , Deptula Bryan 
Published: June 2024

PurposeThis study aims to explore individual leader identity development across four key dimensions: strength, integration, meaning and inclusiveness.Design/methodology/approachAround 70 semi-structured interviews with aspiring and practicing leaders were conducted to gather qualitative data.FindingsThe majority of individuals interviewed showed development or were developing in the dimensions of strength and integration. However, over half of the sample demonstrated underdevelopment in the dimensions of meaning and inclusiveness.Originality/valueThis study contributes to the existing literature by providing nuanced insights into the level and patterns of development across all four dimensions of leader identity within individuals. It reveals that while some symmetry of development across dimensions is possible, it is less prevalent than previously assumed.
Institutional governance priorities to foster exports in Egypt
Authors: Abulata Nermine N. 
Published: June 2024

PurposeThe paper studies types and mechanisms of vertical and horizontal multilevel institutional governance (IG) (multilevel governance [MLG]). The relation with exports is reviewed and quantified to attempt prioritizing institutional reforms fostering merchandise exports in Egypt.Design/methodology/approachThe paper studies data (from 1996 till 2020) to estimate impact of IG on Egyptian merchandise exports using two autoregressive distributed lag (ARDL) models: to test the World Governance Index (WGI) composite index, followed by its main indicators; and to determine governance priorities in Egypt. “Institutional” approach is adopted to assess mechanisms boosting Egyptian exports. Design comprises three sections – (1) conceptual and literature review, (2) main MLG mechanisms and (3) key findings of empirical results – to find out which institutional reforms enhance exports competitiveness in Egypt.FindingsAmong MLG different levels of governance, the macro level is highly related to boosting exports competitiveness. Institutional differentials between countries and regions affect competitive edge. In Egypt, results show that IG priorities that could foster exports are the rule of law, regulatory quality, government effectiveness and political stability and absence of violence.Practical implicationsBy adopting IG mechanisms, i.e. legislative, organizational and digital; and instruments, e.g. National Single Window, Time Release Standards and others, Egyptian exports could reach new heights.Originality/valueExports competitiveness does not rely solely on monetary and fiscal factors; IG dynamics could be more important in Egypt. ARDL model for Egyptian merchandise exports using WGI 2021 dataset.
The moderating roles of healthcare expenditure in the fossil fuel consumption‐ mortality rate conflicts in fossil fuel‐dependent sub‐Saharan African countries
Authors: Omokanmi Olatunde Julius , Ibrahim Ridwan Lanre , Olaoye Olumide Olusegun 
Published: June 2024

AbstractThis current study contributes to the extant literature by providing the first empirical evidence on the functional relationship between fossil fuel consumption, environmental pollution, and mortality rate in selected fossil fuels‐dependent nations in sub‐Saharan African countries with the moderating role of healthcare expenditures from 1982 to 2021. The empirical evidence relies on a battery of techniques comprising fully modified ordinary least squares, dynamic ordinary least squares, and panel quartile regression estimators. In order to establish sturdy empirical insights, fossil fuel is proxy by four indices including oil, coal, natural gas (at the disaggregated level), and fossil fuel (at the aggregated level). Mortality rate is also disaggregated into mortality rate, adult male, mortality rate, adult female, and infant mortality rate. Based on this disaggregation, the findings from the study reveal the following: First, the indicators for fossil fuel consumption have positive statistically significant impact on all three measures of mortality rate. Second, environmental pollution positively impacts the three indicators of mortality rate. Third, healthcare expenditure significantly reduces mortality rate, while its interaction with fossil fuel consumption moderates their unfavorable impacts on mortality rate. Fourth, with the exception of natural gas, the indicators of fossil fuel consumption and environmental pollution exert unfavorable impacts on mortality rate across all the quartiles. Emerging from these empirical findings, the study recommends promotion of cleaner sources of energy while at the same time improving healthcare expenditure as an interim measure pending full transition to renewable energy towards the attainment of a good health outcome in sub‐Saharan Africa countries.
Evidences of neurological injury caused by COVID‐19 from glioma tissues and glioma organoids
Authors: Hu Huimin , Wang Chen , Tao Rui , Liu Bohan , Peng Dazhao , Chen Yankun , Zhang Wei 
Published: June 2024

AbstractIntroductionDespite the extensive neurological symptoms induced by COVID‐19 and the identification of SARS‐CoV‐2 in post‐mortem brain samples from COVID‐19 patients months after death, the precise mechanisms of SARS‐CoV‐2 invasion into the central nervous system remain unclear due to the lack of research models.MethodsWe collected glioma tissue samples from glioma patients who had a recent history of COVID‐19 and examined the presence of the SARS‐CoV‐2 spike protein. Subsequently, spatial transcriptomic analyses were conducted on normal brain tissues, glioma tissues, and glioma tissues from glioma patients with recent COVID‐19 history. Additionally, single‐cell sequencing data from both glioma tissues and glioma organoids were collected and analyzed. Glioma organoids were utilized to evaluate the efficacy of potential COVID‐19 blocking agents.ResultsGlioma tissues from glioma patients with recent COVID‐19 history exhibited the presence of the SARS‐CoV‐2 spike protein. Differences between glioma tissues from glioma patients who had a recent history of COVID‐19 and healthy brain tissues primarily manifested in neuronal cells. Notably, neuronal cells within glioma tissues of COVID‐19 history demonstrated heightened susceptibility to Alzheimer's disease, depression, and synaptic dysfunction, indicative of neuronal aberrations. Expressions of SARS‐CoV‐2 entry factors were confirmed in both glioma tissues and glioma organoids. Moreover, glioma organoids were susceptible to pseudo‐SARS‐CoV‐2 infection and the infections could be partly blocked by the potential COVID‐19 drugs.ConclusionsGliomas had inherent traits that render them susceptible to SARS‐CoV‐2 infection, leading to their representability of COVID‐19 neurological symptoms. This established a biological foundation for the rationality and feasibility of utilization of glioma organoids as research and blocking drug testing model in SARS‐CoV‐2 infection within the central nervous system.
A transdisciplinary approach for assessing connections between soil, food, and people in Aotearoa New Zealand
Authors: Gillespie Julie , Cavanagh Jo‐Anne , Edwards Sarah , Jolly Dyanna , Payne Dione , Smith Carol 
Published: June 2024

AbstractWith increasing urbanisation, there is a growing disconnect between soil, food, and people, centred around those relying on Western food production models. This ‘wicked’ problem is challenging sustainable soil use and food insecurity. Knowledge of soils through scientific studies alone are unable to address this problem, and we need to extend the boundaries of soil science for real progress to be made. We present a conceptual framework for understanding the reciprocal connections between soil, food, and people in local food production systems in Aotearoa New Zealand, applying principles and practices from a transdisciplinary research methodology. The resultant Food‐Landscape Networks framework consists of seven factors that support understanding the inherent connections between soil, food, and people. The factors are: soil health, land suitability, climate, productivity, food quality, well‐being, and engagement. These factors have been identified from weaving together mātauraka (the Kāi Tahu mita [dialect] is used in this text, where the ‘ng’ diagraph is replaced with ‘k’, e.g., mātauranga = mātauraka) Māori (Māori knowledge, culture, worldview, and values) and soil science using the He Awa Whiria, Braided Rivers, epistemological framework. Mātauraka Māori guides the traditionally reductionist discipline of soil science into a more holistic space, in an Aotearoa New Zealand context.