bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic Consequences of Damage Dynamics in Single-Cell Ageing
Authors: Tuğrul Murat , Steiner Ulrich K
Published: May 2023

Ageing is driven by damage accumulation leading to a decline in function over time. In single-cell systems, in addition to this damage accumulation within individuals, asymmetric damage partitioning at cell division can play a crucial role in shaping demographic ageing patterns. Despite empirical single-cell studies providing quantitative data at the molecular and demographic level, a comprehensive theory of how cellular damage production and asymmetric partitioning propagate and influence demographic patterns is still lacking. Here, we present a generic and flexible damage model using a stochastic differential equation approach that incorporates stochastic damage accumulation and asymmetric damage partitioning at cell divisions. We formulate an analytical approximation linking cellular and damage parameters to demographic ageing patterns. Interestingly, the lifespan of cells follows an inverse-gaussian distribution whose underlying properties derive from cellular and damage parameters. We demonstrate how stochasticity (noise) in damage production, asymmetry in damage partitioning, and division frequency shape lifespan distribution. Confronting the model to various empiricalE.colidata reveals non-exponential scaling in mortality rates, a scaling that cannot be captured by classical Gompertz-Makeham models. Our findings provide a deep understanding of how fundamental processes contribute to cellular damage dynamics and generate demographic patterns. Our damage model’s generic nature offers a valuable framework for investigating ageing in diverse biological systems.

Significance

Asymmetries and randomness in cellular events play important roles in establishing the diversity at evolutionary and demographic scales. Looking at single-cells, ageing processes are influenced by stochastic damage accumulation and asymmetric damage partitioning at cell divisions. Utilising stochastic differential equations, we develop a cellular damage model that encapsulate both noisy damage accumulation within cells and asymmetric damage partitioning among cells when they divide. In doing so we bridge molecular stochastic processes, demographic fates of individuals, and population level demographic distributions. Our model aligns with empirical data fromE.colisingle-cell studies and advances our understanding compared to traditional demographic models. The generic and adaptable nature of our model paves the way for broader applications in ageing research across biological systems, highlighting the influences of stochasticity and asymmetry on cellular biology.
Integrating stereotypes and factual evidence in interpersonal communication
Authors: Koch Saskia B. J. , Tyborowska Anna , Niermann Hannah C. M. , Cillessen Antonius H. N. , Roelofs Karin , Bašnáková Jana , Toni Ivan , Stolk Arjen
Published: May 2023

Stereotypes can exert a powerful influence on our interactions with others, potentially leading to prejudice when factual evidence is ignored. Here, we identify neuroanatomical and developmental factors that influence the real-time integration of stereotypes and factual evidence during live social interactions. The study uses precisely quantified communicative exchanges in a longitudinal cohort of seventeen-year-olds followed since infancy, testing their ability to moderate stereotype tendencies toward children as contrary evidence accumulates. Our results indicate that the impact of stereotypes on communicative behavior is linked to individual variations in gray matter density and cortical thickness in the right anterior cingulate gyrus. In contrast, the ability to moderate stereotype tendencies is influenced by developmental exposure to social interactions during the initial years of life, beyond the effects of familial environment and later experiences. These findings pinpoint a key brain structure underlying stereotype tendencies and suggest that early-life social experiences have lasting consequences on how individuals integrate factual evidence in interpersonal communication.
Demographic consequences of an extreme heatwave are mitigated by spatial heterogeneity in an annual monkeyflower
Authors: McDonald Laura M. , Scharnagl Anna , Turcu Andrea K. , Patterson Courtney M. , Kooyers Nicholas J.
Published: May 2023

Heatwaves are becoming more frequent and intense with climate change, but the demographic and evolutionary consequences of heatwaves are rarely investigated in herbaceous plant species. We examine the consequences of a short but extreme heatwave in Oregon populations of the common yellow monkeyflower (Mimulus guttatus) by leveraging a common garden experiment planted with range-wide populations and observational studies of eleven local populations. In the common garden, 89% of seedlings died during the heatwave including >96% of seedlings from geographically-local populations. Some populations from hotter and drier environments had higher fitness, however others from comparable environments performed poorly. Observational studies of local natural populations drastically differed in the consequences of the heatwave - one population was completely extirpated and nearly half had a >50% decrease in fitness. However, a few populations hadgreaterfitness during the heatwave year. Differences in mortality corresponded to the impact of the heatwave on soil moisture – retention of soil moisture throughout the heatwave led to greater survivorship. Our results suggest that not all populations experience the same intensity or degree of mortality during extreme events and such heterogeneity could be important for genetic rescue or to facilitate the distribution of adaptive variants throughout the region.
The carbapenem inoculum effect provides insight into the molecular mechanisms underlying carbapenem resistance inEnterobacterales
Authors: Cartagena Alexis Jaramillo , Taylor Kyra L. , Smith Joshua T. , Manson Abigail L. , Pierce Virginia M. , Earl Ashlee M. , Bhattacharyya Roby P.
Published: May 2023

Carbapenem-resistantEnterobacterales(CRE) are important pathogens that can develop resistance via multiple molecular mechanisms, including hydrolysis or reduced antibiotic influx. Identifying these mechanisms can improve pathogen surveillance, infection control, and patient care. We investigated how resistance mechanisms influence the carbapenem inoculum effect (IE), a phenomenon where inoculum size affects antimicrobial susceptibility testing (AST). We demonstrated that seven different carbapenemases impart a meropenem IE inEscherichia coli. Across 110 clinical CRE isolates, the carbapenem IE strictly depended on resistance mechanism: all carbapenemase-producing CRE (CP-CRE) exhibited a strong IE, whereas porin-deficient CRE displayed none. Concerningly, 50% and 24% of CP-CRE isolates changed susceptibility classification to meropenem and ertapenem, respectively, across the allowable inoculum range in clinical guidelines. The meropenem IE, and the ratio of ertapenem to meropenem minimal inhibitory concentration (MIC) at standard inoculum, reliably identified CP-CRE. Understanding how resistance mechanisms affect AST could improve diagnosis and guide therapies for CRE infections.
Enhanced Annotation of CD45RA to Distinguish T cell Subsets in Single Cell RNA-seq via Machine Learning
Authors: Ran Ran , Brubaker Douglas K.
Published: May 2023

T cell heterogeneity presents a challenge for accurate cell identification, understanding their inherent plasticity, and characterizing their critical role in adaptive immunity. Immunologists have traditionally employed techniques such as flow cytometry to identify T cell subtypes based on a well-established set of surface protein markers. With the advent of single-cell RNA sequencing (scRNA-seq), researchers can now investigate the gene expression profiles of these surface proteins at the single-cell level. The insights gleaned from these profiles offer valuable clues and a deeper understanding of cell identity. However, CD45RA, the isoform of CD45 which distinguish between naïve/central memory T cells and effector memory/effector memory cells re-expressing CD45RA T cells, cannot be well profiled by scRNA-seq due to the difficulty in mapping short reads to genes. In order to facilitate cell type annotation in T cell scRNA-seq analysis, we employed machine learning and trained a CD45RA+/-classifier on single-cell mRNA count data annotated with known CD45RA antibody levels provided by cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) data. Among all algorithms we tested, the trained support vector machine (SVM) with a radial basis function (RBF) kernel with optimized hyperparameters achieved a 99.96% accuracy on an unseen dataset. The multilayer Perceptron (MLP) classifier, the second most predictive method overall, also achieved a decent accuracy of 99.74%. Our simple yet robust machine learning approach provides a valid inference on the CD45RA level, assisting the cell identity annotation and further exploring the heterogeneity within human T cells.
On the cusp of adaptive change: the hierarchical radiation of phyllostomid bats
Authors: Grossnickle David M. , Sadier Alexa , Patterson Edward , Cortés-Viruet Nashaly N. , Rivera Stephanie Jimenez , Sears Karen E. , Santana Sharlene E.
Published: May 2023

Adaptive radiations are bursts in biodiversity that lead to the origin of new evolutionary lineages and phenotypes. However, adaptive radiations typically occur over millions of years and it is unclear how the macroevolutionary dynamics that underpin them vary through time and among groups of organisms. Phyllostomid bats radiated extensively for diverse diets –from insects to vertebrates, fruit, nectar, and blood– and we use their molars as a model system to examine the dynamics of adaptive radiations. Three-dimensional shape analyses of lower molars of Noctilionoidea (Phyllostomidae and close relatives) indicate that different diet groups exhibit distinct morphotypes. Comparative analyses further reveal that phyllostomids are a striking example of a hierarchical radiation; their initial, higher-level diversification involved an ‘early burst’ in molar morphological disparity as lineages invaded new diet-affiliated adaptive zones, followed by subsequent lower-level diversifications within adaptive zones involving less dramatic morphological changes. We posit that strong selective pressures related to initial shifts to derived diets may have freed molars from morpho-functional constraints associated with the ancestral molar morphotype. Then, lineages with derived diets (frugivores and nectarivores) diversified considerably within broad adaptive zones, likely reflecting finer-scale niche partitioning. The observed early burst pattern is only evident when examining molar traits that are strongly linked to diet, highlighting the importance of ecomorphological traits in comparative studies. Our results support the hypothesis that adaptive radiations are commonly hierarchical and involve different tempos and modes at different phylogenetic scales, with early bursts being more common at broader scales.

SIGNIFICANCE STATEMENT

Many groups of organisms are exceptionally diverse in their ecology, morphology, and number of species. But there is debate as to whether these groups commonly achieved this diversity through ‘bursts’ in diversification early in their history. Phyllostomid bats are one of the most ecologically diverse mammalian families and a classic example of an adaptive radiation. We use their molar shapes, which correlate with diet, as a model for examining macroevolutionary patterns during diversifications. We find that phyllostomids experienced a two-step process of diversification; the first step involved a rapid burst, whereas the second involved finer-scale changes as lineages filled ecological niches. We posit that this is a common, yet underappreciated, pattern during the early histories of many diverse clades.
Spp1 secreted by macrophages impairs osteogenic ability of Ctsk+Fmod+periosteal cells in jaw bone
Authors: Yi Zumu , Liu Yeyu , Wang Jing , Hu Chen , Man Yi
Published: May 2023

Periosteum, which covers the surface of most bones, mediates bone regeneration through endochondral ossification during fracture repair and intramembranous ossification under steady state. Periosteal cells (PCs) of jaw bones are different from those of long bones in phenotypic characteristics and functions. So far, the role of periosteum in jaw bones during bone grafting remain unclarified. Here we propose a subperiosteal bone grafting model based on the clinical procedures. By integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic (ST), we found a functional Ctsk+Fmod+subset of PCs in jaw bones. The Ctsk+Fmod+PCs had the potential of multi-directional differentiation. Furthermore, Spp1 secreted by macrophages could impair the osteogenic capacity of Ctsk+Fmod+PCs, which could be partly rescued by blocking Spp1. The identification of this Ctsk+Fmod+subclusters, which shows osteoprogenitor characteristics and close interaction with macrophages, reveals the heterogeneity of periosteal cells in jaw bones, and may provide target of intervention to improve osteogenesis during bone augmentation surgery.
The unexpected loss of the “hunger hormone” ghrelin in true passerines: A game changer in migration physiology
Authors: Prost Stefan , Elbers Jean P. , Slezacek Julia , Fuselli Silvia , Smith Steve , Fusani Leonida
Published: May 2023

Migratory birds must accumulate large amounts of fat prior to migration to sustain long flights. In passerines, the small body size limits the amount of energy stores that can be transported and therefore birds undergo cycles of extreme fattening and rapid exhaustion of reserves. Research on these physiological adaptations was rattled by the discovery that birds have lost the main vertebrate regulator of fat deposition,leptin. Recent studies have thus focused onghrelin, known as the “hunger hormone”, a peptide secreted by the gastrointestinal tract to regulate food intake, body mass, and other important functions in vertebrates. Studies on domestic species showed that in birdsghrelinhas effects opposite to those described in mammals, such as inhibiting instead of promoting food intake. Furthermore, a series of recent studies have shown thatghrelinadministration influences migratory behaviour in passerine birds, suggesting an important role of this hormone in bird migration. However, using comparative genomic analyses we show thatghrelinhas been lost in the largest avian taxon Eupasseres, after the basic split from Acanthisitti about 50 million years ago. Eupasserines, also known as True passerines, include all but two of the ca. 10,000 known passerine species. We further found that theghrelinreceptor (growth hormone secretagogue receptor, GHS-R) is still conserved in passerine birds, as indicated by sites under purifying selection and in line with the effects ofghrelinadministration. Thus,ghrelinadds to a list of hormones highly conserved in vertebrates that have lost their main functions in specific taxa. The maintenance of a functional receptor system, however, suggests that in eupasserine birds another ligand has replacedghrelin, perhaps to bypass the feedback system that would hinder large pre-migratory accumulation of subcutaneous fat.
De novomotor learning creates structure in neural activity space that shapes adaptation
Authors: Chang Joanna C. , Perich Matthew G. , Miller Lee E. , Gallego Juan A. , Clopath Claudia
Published: May 2023

Animals can quickly adapt learned movements in response to external perturbations. Motor adaptation is likely influenced by an animal’s existing movement repertoire, but the nature of this influence is unclear. Long-term learning causes lasting changes in neural connectivity which determine the activity patterns that can be produced. Here, we sought to understand how a neural population’s activity repertoire, acquired through long-term learning, affects short-term adaptation by modeling motor cortical neural population dynamics duringde novolearning and subsequent adaptation using recurrent neural networks. We trained these networks on different motor repertoires comprising varying numbers of movements. Networks with multiple movements had more constrained and robust dynamics, which were associated with more defined neural ‘structure’—organization created by the neural population activity patterns corresponding to each movement. This structure facilitated adaptation, but only when small changes in motor output were required, and when the structure of the network inputs, the neural activity space, and the perturbation were congruent. These results highlight trade-offs in skill acquisition and demonstrate how prior experience and external cues during learning can shape the geometrical properties of neural population activity as well as subsequent adaptation.
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine
Authors: MacMillen Zachary , Hatzakis Kiara , Simpson Adrian , Shears Melanie J. , Watson Felicia , Erasmus Jesse H. , Khandhar Amit P. , Wilder Brandon , Murphy Sean C. , Reed Steven G. , Davie James W. , Avril Marion
Published: May 2023

Malaria, caused byPlasmodiumparasites, remains one of the most devastating infectious diseases worldwide, despite control efforts that have lowered morbidity and mortality. The onlyP. falciparumvaccine candidates to show field efficacy are those targeting the asymptomatic pre-erythrocytic (PE) stages of infection. The subunit (SU) RTS,S/AS01 vaccine, the only licensed malaria vaccine to date, is only modestly effective against clinical malaria. Both RTS,S/AS01 and the SU R21 vaccine candidate target the PE sporozoite (spz) circumsporozoite (CS) protein. These candidates elicit high-titer antibodies that provide short-term protection from disease, but do not induce the liver-resident memory CD8+T cells (Trm) that confer strong PE immunity and long-term protection. In contrast, whole-organism (WO) vaccines, employing for example radiation-attenuated spz (RAS), elicit both high antibody titers and Trm, and have achieved high levels of sterilizing protection. However, they require multiple intravenous (IV) doses, which must be administered at intervals of several weeks, complicating mass administration in the field. Moreover, the quantities of spz required present production difficulties. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. While the priming dose is a self-replicating RNA encodingP. yoeliiCS protein, delivered via an advanced cationic nanocarrier (LIONTM), the trapping dose consists of WO RAS. This accelerated regime confers sterile protection in theP. yoeliimouse model of malaria. Our approach presents a clear path to late-stage preclinical and clinical testing of dose-sparing, same-day regimens that can confer sterilizing protection against malaria.
Functional Subtypes of Synaptic Dynamics in Mouse and Human
Authors: Beninger John , Rossbroich Julian , Tóth Katalin , Naud Richard
Published: May 2023

Synapses show preferential responses to particular temporal patterns of activity. Across individual synapses, there is a large degree of response heterogeneity that is informally or tacitly separated into classes, and typically only two: facilitating and depressing short-term plasticity. Here we combined a kernel-based model and machine learning techniques to infer the number and the characteristics of functionally distinct subtypes of short-term synaptic dynamics in a large dataset of glutamatergic cortical connections. To this end, we took two independent approaches. First, we used unsupervised techniques to group similar synapses into clusters. Second, we used supervised prediction of cell subclasses to reveal features of synaptic dynamics that characterized cellular genetic profiles. In rodent data, we found five clusters with a remarkable degree of convergence with the transgenic-associated subtypes. Two of these clusters corresponded to different degrees of facilitation, two corresponded to depression with different degrees of variability and one corresponded to depression-then-facilitation. Strikingly, the application of the same clustering method in human data inferred highly similar clusters to those observed in rodents, supportive of a stable clustering procedure and suggesting a homology of functional subtypes across species. This nuanced dictionary of functional subtypes shapes the heterogeneity of cortical synaptic dynamics and provides a lens into the basic motifs of information transmission in the brain.
Embryonic organizer specification in the mud snailIlyanassa obsoletadepends on intercellular signaling
Authors: Wandelt Jessica E. , Nakamoto Ayaki , Goulding Morgan Q , Nagy Lisa M.
Published: May 2023

In early embryos of the neogastropodIlyanassa obsoleta, cytoplasmic segregation of a polar lobe is required for establishment of the D macromere, empowering its great-granddaughter macromere 3D to act as a single-celled organizer that induces body patterning along the secondary axis. We present evidence that polar lobe inheritance is not sufficient to specify 3D potential, but rather makes the D macromere lineage responsive to some intercellular signal(s) required for activating the special properties of 3D. Experimental removal of micromeres results in loss of organizer-linked MAPK activation, complete and specific defects of organizer-dependent larval organs, and progressive cell cycle retardation leading to equalization of the normally accelerated division schedule of 3D. Ablation of the second-quartet micromere 2d greatly potentiates the effects of first-quartet micromere ablation. Our findings link 3D establishment inI. obsoletato the putative ancestral spiralian mechanism in which a signal from micromeres leads to specification of 3D among four initially equivalent macromeres.

Summary Statement

Cell ablation experiments on embryos of the snailIlyanassareveal that specification of the organizer cell 3D depends on cell-extrinsic cues as well as polar lobe inheritance.
Generation of aPlasmodium falciparumreporter line for studies of parasite biology throughout the life cycle
Authors: Suárez-Cortés Pablo , Costa Giulia , Andres Manuela , Eyermann Daniel , Kreschel Cornelia , Spohr Liane , Goosmann Christian , Brinkmann Volker , Levashina Elena A.
Published: May 2023

Fluorescence reporter strains of human malaria parasites are powerful tools to study the interaction of the parasites with both human and mosquito hosts. However, low fluorescence intensity in transmission-relevant parasite stages and the choice of insertion loci that cause parasite developmental defects in the mosquito largely limits usefulness of currently available lines. To overcome these limitations, we used a CRISPR-Cas9-mediated approach to generatePfOBC13GFP, a novel selection marker-free reporter parasite in the background of the African NF54Plasmodium falciparumline. As docking site, we selected theOBC13locus that is dispensable for asexual and sexual developmentin vitro.PfOBC13GFPparasites encode GFP flanked byhsp70UTRs that drive strong fluorescence reporter expression throughout blood and mosquito stages, enabling parasite detection by such high throughput methods as flow cytometry. When compared to the parental line,PfOBC13GFPparasites showed normal development during blood and mosquito stages, and they efficiently infected the main African vectorAnopheles coluzzii,overcoming one of the limitations of the previously developed fluorescent reporter lines based on thePfs47locus.PfOBC13GFPconstitutes a potent tool enabling host-pathogen studies throughoutPlasmodiumlife cycle.

Importance

Fluorescence reporter strains have been very useful in malaria research, however, up to date they had limitations in mosquito infectivity and fluorescence intensity. Here we report the generation ofPfOBC13GFP, a new fluorescent parasite strain of the human malaria parasiteP. falciparum.PfOBC13GFPparasites are highly fluorescent throughout the life cycle, making them an ideal tool for the study the parasite progression through blood and mosquito stages. They efficiently infect the African mosquitovector A. coluzzii, allowing the study of this African parasite in its biological background. Moreover, strong parasite fluorescence enables flow cytometry and live microscopy characterization of all parasite stages, especially those involved in transmission.
Transposon dynamics in the emerging oilseed cropThlaspi arvense
Authors: Contreras-Garrido Adrián , Galanti Dario , Movilli Andrea , Becker Claude , Bossdorf Oliver , Drost Hajk-Georg , Weigel Detlef
Published: May 2023

Genome evolution is partly driven by the mobility of transposable elements (TEs) which often leads to deleterious effects, but their activity can also facilitate genetic novelty and catalyze local adaptation. We explored how the intraspecific diversity of TE polymorphisms is shaping the broad geographic success and adaptation capacity of the emerging oil cropThlaspi arvense. We achieved this by classifying the TE inventory of this species based on a high-quality genome assembly, age estimation of retrotransposon TE families and a comprehensive assessment of their mobilization potential. Our survey of TE insertion polymorphisms (TIPs) captured 280 accessions from 12 regions across the Northern hemisphere. We quantified over 90,000 TIPs, with their distribution mirroring genetic differentiation as measured by single nucleotide polymorphisms (SNPs). The number and types of mobile TE families vary substantially across populations, but there are also shared patterns common to all accessions. We found that Ty3/Athila elements are the main drivers of TE diversity inT. arvensepopulations, while a single Ty1/Alesia lineage might be particularly important for molding transcriptome divergence. We further observed that the number of retrotransposon TIPs is associated with variation at genes related to epigenetic regulation while DNA transposons are associated with variation at a Heat Shock Protein (HSP19). We propose that the high rate of mobilization activity can be harnessed for targeted gene expression diversification, which may ultimately present a toolbox for the potential use of transposition in breeding and domestication ofT. arvense.
All-optical interrogation of brain-wide activity in freely swimming larval zebrafish
Authors: Chai Yuming , Qi Kexin , Wu Yubin , Li Daguang , Tan Guodong , Guo Yuqi , Chu Jun , Mu Yu , Shen Chen , Wen Quan
Published: May 2023

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in freely swimming larval zebrafish. The system consists of three main components: a 3D tracking module, a dual color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca2+activity from signals contaminated by motion artifacts. The method also incorporates rapid 3D image reconstruction and registration, facilitatingreal-timeselective optogenetic stimulation of different regions of the brain. By demonstrating that selective light activation of the midbrain regions in larval zebrafish could reliably trigger biased turning behavior and changes of brain-wide neural activity, we present a valuable tool for investigating the causal relationship between distributed neural circuit dynamics and naturalistic behavior.

Highlights

We develop an all-optical technique that enables simultaneous whole brain imaging and optogenetic manipulation of selective brain regions in freely behaving larval zebrafish.

A combination of a genetically encoded calcium indicator and a long Stokes-shift red fluorescence protein, together with the adaptive filter algorithm, enables us to reliably distinguish calcium activity from motion-induced signal contamination.

Rapid 3D image reconstruction and registration enables real-time targeted optogenetic stimulation of distinct brain regions in a freely swimming larval zebrafish.
cytoviewer:an R/Bioconductor package for interactive visualization and exploration of highly multiplexed imaging data
Authors: Meyer Lasse , Eling Nils , Bodenmiller Bernd
Published: May 2023

Highly multiplexed imaging enables single-cell-resolved detection of numerous biological molecules in their spatial tissue context. Interactive data visualization of multiplexed imaging data is necessary for quality control and hypothesis examination. Here, we describecytoviewer, an R/Bioconductor package for interactive visualization and exploration of multi-channel images and segmentation masks. Thecytoviewerpackage supports flexible generation of image composites, allows side-by-side visualization of single channels, and facilitates the spatial visualization of single-cell data in the form of segmentation masks. The package operates onSingleCellExperiment, SpatialExperimentandCytoImageListobjects and therefore integrates with the Bioconductor framework for single-cell and image analysis. Users ofcytoviewerneed little coding expertise, and the graphical user interface allows user-friendly navigation. We showcase the functionality ofcytoviewerby analysis of an imaging mass cytometry dataset of cancer patients.

Availability

Thecytoviewerpackage can be installed from Bioconductor viahttps://www.bioconductor.org/packages/release/bioc/html/cytoviewer.html. The development version and further instructions can be found on GitHub athttps://github.com/BodenmillerGroup/cytoviewer. We provide an R script to exemplify the usage ofcytoviewerin the supplementary information.

Supplementary informations

Supplementary data are available online.
YAP/TAZ are Crucial Regulator of Macrophage-mediated Pulmonary Inflammation and Fibrosis after Bleomycin-induced Injury
Authors: Mia Masum M. , Abdul Ghani Siti Aishah Binte , Cibi Dasan Mary , Bogireddi Hanumakumar , Wong Wai Shiu Fred , Singh Manvendra K.
Published: May 2023

Pulmonary fibrosis (PF) is the most common form of end stage interstitial devastating lung disease characterized by the scarring of lung due to excessive production of extracellular matrix (ECM). Recent studies have revealed the impact of macrophages in inflammation-induced fibrosis and distinct subsets of macrophages differentially contributes to the development of PF. However, the regulatory mechanisms and proinflammatory/profibrotc behaviour of heterogeneous population of lung macrophages during fibrogenesis remain incompletely understood. Here, we demonstrate the macrophage-specific role of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in the development of bleomycin-induced inflammation and PF in mice. Both YAP/TAZ are activated in lung macrophages of fibrotic patients and of mice after bleomycin-induced injury. Myeloid-specific genetic deletion ofYap/Tazresulted in reduced recruitment of monocyte-derived alveolar macrophages (Mo-AMs), leading to an impaired inflammatory response, reduced PF and improved regeneration of alveolar epithelial cells in bleomycin-injured lung. However, overexpression ofYapin macrophages augmented the Mo-AMs recruitment in lung leading to increased proinflammatory response, exacerbated fibrotic response and decreased regeneration of alveolar epithelial cells in bleomycin-injured lung. We demonstrate that YAP/TAZ regulate PF through the activation of macrophage recruitment driver C-C motif chemokine ligand 2 (CCL2) and blocking of CCL2 with neutralizing antibody prevented YAP-induced inflammatory and fibrotic response. We also demonstrate that YAP/TAZ regulate macrophage polarization as well as macrophage-fibroblasts crosstalk by regulating expression of Methyl-CpG–binding domain 2 (MBD2) during bleomycin-induced PF. Taken together, we show that YAP/TAZ are potent regulators of macrophage polarization, infiltration and macrophage–mediated proinflammatory/profibrotic response during PF.
Method to detect the bolt thread defect in the aerospace vehicle with ultrasonic image and its implementation
Authors: Liu Chunhua , Li Ming , Chen Peng , Zhang Chaoyun
Published: May 2023

Purpose

This study aims to solve the problems of ambiguous localization, large calculation, poor real-time and limited applicability of bolt thread defect detection.

Design/methodology/approach

First, the acquired ultrasound image is used to acquire the larger area of the image, which is set as the compliant threaded area. Second, based on the determined coordinates of the center point in each selected region, the set of coordinates on the left and right sides of the bolts is acquired by DBSCAN method with parameters eps and MinPts, which is determined by data set dimension D and the k-distance curve. Finally, the defect detection boundary line fitting is completed using the acquired coordinate set, and the relationship between the distance from each detection point to the curve and d, which is obtained from the measurement of the standard bolt sample with known thread defect, is used to locate the bolt thread defect simultaneously.

Findings

In this paper, the bolt thread defect detection method with ultrasonic image is proposed; meanwhile, the ultrasonic image acquisition system is designed to complete the real-time localization of bolt thread defects.

Originality/value

The detection results show that the method can effectively detect bolt thread defects and locate the bolt thread defect location with wide applicability, small calculation and good real-time performance.
Estimation of the wind drift factor and uncertainty analysis based on CFD computer simulations
Authors: Sbragio Ricardo , Martins Marcelo Ramos
Published: May 2023

Purpose

The purpose of this work is to present a procedure for determining the wind drift factor through two-dimensional computational fluid dynamics (CFD) simulations of the wind acting on a wavy sea surface, such that the subjectivity of its estimation is reduced.

Design/methodology/approach

The wind drift factor was determined by two-dimensional CFD analyses with open-channel condition. The characteristic wave was determined by the Sverdrup–Munk–Bretschneider (SMB) method. The uncertainty analysis is based on convergence studies using a single parameter refinement (grid and time step).

Findings

This procedure allows the estimation of the wind drift factor in a fetch-limited domain. The domain's value in the analyzed region is 0.0519 ± 4.92% which is consistent with the upper values of the wind drift factors reported in the literature.

Research limitations/implications

The use of a three-dimensional domain was impractical with the available computational resources because of the fine mesh required for wave modeling. The uncertainty analysis consisted only of a verification procedure. Validation against real data was not possible because of the lack of measured data in the analyzed region.

Originality/value

The wind drift factor is usually estimated based on either experience or random sampling. The original contribution of this work is the presentation of a CFD procedure for estimating the wind drift factor, in which the domain inlet is subjected to a wave boundary condition and to a wind velocity.
The impact of energy certificates on sales and rental prices: a comparative analysis
Authors: Gerassimenko Alesia , Defau Laurens , De Moor Lieven
Published: May 2023

Purpose

The current literature on energy certificates shows that Energy Performance Certificate labels have an important effect on real estate prices. However, interestingly, the limited studies that address the rental market find significantly lower price premiums than the sales market. The purpose of this paper is to add to this literature, by doing a comparative analysis of price premiums in the sales and rental market in Flanders (Belgium).

Design/methodology/approach

This study uses a hedonic regression model to analyze 177,670 real estate listings between 2016 and 2021. The data is provided by Immoweb – the largest online real estate platform in Belgium. The data set was divided in sold and rented properties: the authors evaluated 126,217 sales listings and 51,453 rent listings.

Findings

The results confirm that energy efficient properties generate a price premium, but that this premium is significantly larger in the sales market than in the rental market. In addition, the findings indicate that both investors and landlords could benefit strongly from renovating dwellings – especially when renovating from an F label to an A label.

Originality/value

Previous research focuses strongly on the sales market, although in many countries the rental market is similar in size and responsible from much energy consumption. Interestingly, the few studies that are addressing the rental market, find singificantly smaller price premiums than in the sales market. The findings add to this literature tradition and offer a comparative analysis of price premiums in the sales and rental market in Flanders. This allows us to not only show the similarities between both markets but also highlight the differences – creating valuable insights for academia, governments and real estate professionals.
Adult safeguarding in Ireland: a critical review of context and gaps
Authors: Phelan Amanda
Published: May 2023

Purpose

The purpose of this paper is to critically review the context of adult protection in Ireland with a focus on older people. The paper traces advances and current limitations in policy, regulation, practice and legislation.

Design/methodology/approach

A review of historical and current contexts in adult safeguarding in Ireland is presented with consideration of key public reviews and commentaries related to care provision, governance and the legislative status of adults at risk.

Findings

While Ireland’s journey to provide adult safeguarding responses for older people has progressed since 2002, there remain many gaps. Further work needs to be addressed urgently to enable a comprehensive alignment of fit-for-purpose, responsive legislation, practice and policy to meet the complex and diverse needs of an increasing ageing population who may require safeguarding support. This includes fostering robust inter-sectorial collaboration, safeguarding legislation and cultural change related to human rights approaches.

Research limitations/implications

The paper is a discussion on the context of adults safeguarding in relation to practice, policy and legislation.

Practical implications

Identifies the need for significant reform in the Irish system of health service. Argues for an overarching, inter-sectorial approach to addressing adult safeguarding, which focuses on prevention as well as early intervention.

Originality/value

The paper offers a review of the current diverse elements comprising current adult safeguarding and older people in Ireland and integrates legislative, regulatory, policy and practice realities. Challenges are illustrated within the context of reactive rather than proactive safeguarding agendas which are linked to public scandals and debates. The paper argues for a more integrated and robust inter-sectorial approach to safeguarding underpinned by adult safeguarding legislation and an overarching governance structure.
The African continental free trade area: the road ahead for the continent’s bold integration project
Authors: Hagos Bereket Alemayehu
Published: May 2023

Purpose

This paper aims to examine the road ahead for the African Continental Free Trade Area (AfCFTA), focusing on its potential opportunities and challenges. It is intended to help the AfCFTA’s effective implementation by highlighting the major areas of intervention for State Parties.

Design/methodology/approach

The paper analyses relevant economic, political and legal research sources on regional integration in Africa and offers some personal views of the author to evaluate the past, present and future of the AfCFTA.

Findings

The paper shows that the AfCFTA can support its State Parties’ industrialization and diversification, better integrate micro-, small- and medium-sized enterprises (MSMEs) to regional value chains, create jobs, encourage sustainable investments and help its State Parties have common positions on global issues and achieve development. But, it also shows the challenges facing the AfCFTA, which include infrastructure gap, revenue and job losses, overlapping membership of State Parties in Regional Economic Communities, cumbersome customs systems, difficulty to cross African borders, fledgling MSMEs and inadequate technical capacity on trade policy. Accordingly, it recommends that State Parties continuously take various actions to address these challenges and maximize the multiple benefits of the AfCFTA.

Originality/value

The paper provides a comprehensive and up-to-date appraisal of the opportunities and challenges of the AfCFTA, both in the context of the history of regional integration in Africa and the recent global shocks that adversely impacted the continent (COVID-19 and the war in Ukraine).
Key aspects of sustainability reporting quality and the future of GRI
Authors: Luque-Vílchez Mercedes , Cordazzo Michela , Rimmel Gunnar , Tilt Carol A.
Published: May 2023

Purpose

This paper aims to investigate the current state of knowledge in key reporting aspects in relation to sustainability reporting in general and to reflect on their relevance to Global Reporting Initiative (GRI) in particular. In doing so, the major gaps in that knowledge are identified, and the paper proceeds to suggest further research avenues.

Design/methodology/approach

The authors conduct a review of papers published in leading journals concerning sustainability reporting to analyse the progress in the literature regarding three important reporting topics: materiality, comparability and assurance.

Findings

The review conducted in this study shows that there is still work to be done to ensure high-quality and consistent sustainability reporting. Key takeaways from the review of the extant literature are as follows: there is ongoing debate about the nature of sustainability reporting materiality, and single versus double materiality. Clearer guidance and better contextualisation are seen as essential for comparability, and, as GRI suggests, there is an important link to materiality that needs to be considered. Finally, assurance has not been mandatory under the GRI, but the current development at EU level might lead to the GRI principles being incorporated in the primary assurance standards.

Practical implications

In this paper, the authors review and synthesise the previous literature on GRI reporting dealing with three key reporting aspects.

Social implications

The authors extract some takeaways from the literature on materiality, comparability and assurance that will all be key challenges for GRI in the future.

Originality/value

This paper provides an updated review of the literature on GRI reporting dealing with three key reporting aspects.
How do ecotourists co-create value on digital platforms? The moderating role of ecotourist typology
Authors: Hernández-López Laura , Del Barrio-García Salvador , Prados-Peña Maria Belen
Published: May 2023

Purpose

This study aims to examine the process of value co-creation (VCC) on digital ecotourism platforms and the role of perceived platform usefulness and user participation behavior in that process. The study also seeks to determine the extent to which the typology of the ecotourist moderates VCC.

Design/methodology/approach

A total of 420 users of a digital ecotourism platform participated in a study analyzing the factors that influence VCC. A mediation, moderation and conditional process analysis was used to test the proposed hypotheses. A K-means cluster analysis was also used to classify the ecotourists into four groups.

Findings

The results show that perceived platform usefulness has a strong influence on the generation of VCC and also on user participation behavior. In turn, user participation behavior is an important driver of VCC. This study also highlights the moderating role of the ecotourist typology in the formation of VCC on these digital platforms.

Practical implications

This study offers managers of digital ecotourism platforms a means to identify and motivate those ecotourists with the necessary skills and characteristics to become true co-creators of value.

Originality/value

This study contributes to the existing knowledge on how value is co-created on digital ecotourism platforms, confirming the important antecedent role of perceived platform usefulness and user participation behavior, as well as the moderating role of ecotourist typology.
Limit equilibrium slope stability analysis of column-supported embankment on weak ground
Authors: R.S.V. Rashma , B.R. Jayalekshmi , R. Shivashankar
Published: May 2023

Purpose

The study aims to analyse the stability of embankments over the improved ground with stone column (SC) and pervious concrete column (PCC) inclusions using limit equilibrium method. The short-term stability of PCC-supported embankment system is rarely addressed. Therefore, the factor of safety (FOS) of column-supported embankment system is calculated using individual column and equivalent area models.

Design/methodology/approach

The stability analysis of column-supported embankment system is conducted using PLAXIS LE 2D. The various geometrical and shear strength parameters influencing the FOS of these embankment systems such as diameter of columns, spacing between columns, embankment height, friction angle of column material, undrained cohesion of weak ground and cohesion of PCC are considered.

Findings

The critical failure envelope of PCC-supported embankment system is observed to be of toe failure, whereas the failure envelope of stone column-supported embankment system is generally of deep-seated nature.

Originality/value

It is found that for PCC embankment system, FOS and failure envelope are not influenced by the geometrical/shear strength parameters other than height of embankment. However, for stone column-supported embankment system, FOS and failure envelope are dependent on all the shear strength and geometrical parameters considered in this study.
Human Trafficking: Iconic Victims, Folk Devils and the Nationality and Borders Act 2022
Authors: Haynes Jason
Published: May 2023

On 28 April 2022, the Westminster Parliament passed the controversial Nationality and Borders Act. The Act is the single biggest overhaul of the UK's immigration system in decades. The Act aims to deter illegal entry into the UK; remove more easily those with no right to be in the UK; and increase the overall fairness of the system. Notwithstanding these seemingly laudable objectives, however, this article argues that the Act represents a retrograde step in the protection of victims of human trafficking. Relying upon Nils Christie's ‘ideal/iconic victims’ and Stanley Cohen's ‘folk devils’ critique, the article contends that, in an age of heightened securitisation and moral panics, the Act will create ‘folk devils’ of victims of trafficking who do not self‐identify, and unduly penalise victims of trafficking who have committed offences in the course, or as a consequence, of being trafficked.