bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods for decoding cortical gradients of functional connectivity
Authors: Peraza Julio A. , Salo Taylor , Riedel Michael C. , Bottenhorn Katherine L. , Poline Jean-Baptiste , Dockès Jérôme , Kent James D. , Bartley Jessica E. , Flannery Jessica S. , Hill-Bowen Lauren D. , Lobo Rosario Pintos , Poudel Ranjita , Ray Kimberly L. , Robinson Jennifer L. , Laird Robert W. , Sutherland Matthew T. , de la Vega Alejandro , Laird Angela R.
Published: August 2023

Macroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a two-segment solution determined by a k-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Finally, we proposed a method for decoding additional components of the gradient decomposition. The current work aims to provide recommendations on best practices and flexible methods for gradient-based functional decoding of fMRI data.
Conductive microgel annealed scaffolds enhance myogenic potential of myoblastic cells
Authors: Casella Alena , Lowen Jeremy , Shimamoto Nathan , Griffin Katherine H. , Filler Andrea C. , Panitch Alyssa , Leach J. Kent
Published: August 2023

Bioelectricity is an understudied phenomenon to guide tissue homeostasis and regeneration. Conductive biomaterials may capture native or exogenous bioelectric signaling, but incorporation of conductive moieties is limited by cytotoxicity, poor injectability, or insufficient stimulation. Microgel annealed scaffolds are promising as hydrogel-based materials due to their inherent void space that facilitates cell migration and proliferation better than nanoporous bulk hydrogels. We generated conductive microgels from poly(ethylene) glycol and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) to explore the interplay of void volume and conductivity on myogenic differentiation. PEDOT:PSS increased microgel conductivity over 2-fold while maintaining stiffness, annealing strength, and viability of associated myoblastic cells. C2C12 myoblasts exhibited increases in the late-stage differentiation marker myosin heavy chain as a function of both porosity and conductivity. Myogenin, an earlier marker, was influenced only by porosity. Human skeletal muscle derived cells exhibited increasedMyod1, IGF-1, and IGFBP-2 at earlier timepoints on conductive microgel scaffolds compared to non-conductive scaffolds. They also secreted higher levels of VEGF at early timepoints and expressed factors that led to macrophage polarization patterns observed during muscle repair. These data indicate that conductivity aids myogenic differentiation of myogenic cell lines and primary cells, motivating the need for future translational studies to promote muscle repair.
R2ROC: An efficient method of comparing two or more correlated AUC from out-of-sample prediction using polygenic scores
Authors: Momin Md. Moksedul , Wray Naomi R , Lee S. Hong
Published: August 2023

Polygenic risk scores (PRSs) enable early prediction of disease risk. Evaluating PRS performance for binary traits commonly relies on the area under the receiver operating characteristic curve (AUC). However, the widely used DeLong’s method for comparative significance tests suffer from limitations, including computational time and the lack of a one-to-one mapping between test statistics based on AUC andR2. To overcome these limitations, we propose a novel approach that leverages the Delta method to derive the variance and covariance of AUC values, enabling a comprehensive and efficient comparative significance test. Our approach offers notable advantages over DeLong’s method, including reduced computation time (up to 150-fold), making it suitable for large-scale analyses and ideal for integration into machine learning frameworks. Furthermore, our method allows for a direct one-to-one mapping between AUC andR2values for comparative significance tests, providing enhanced insights into the relationship between these measures and facilitating their interpretation. We validated our proposed approach through simulations and applied it to real data comparing PRSs for diabetes and coronary artery disease (CAD) prediction in a cohort of 28,880 European individuals. The PRSs were derived using genome-wide association study summary statistics from two distinct sources. Our approach enabled a comprehensive and informative comparison of the PRSs, shedding light on their respective predictive abilities for diabetes and CAD. This advancement contributes to the assessment of genetic risk factors and personalized disease prediction, supporting better healthcare decision-making.
Continuous lifelong learning for modeling of gene regulation from single cell multiome data by leveraging atlas-scale external data
Authors: Yuan Qiuyue , Duren Zhana
Published: August 2023

Accurate context-specific Gene Regulatory Networks (GRNs) inference from genomics data is a crucial task in computational biology. However, existing methods face limitations, such as reliance on gene expression data alone, lower resolution from bulk data, and data scarcity for specific cellular systems. Despite recent technological advancements, including single-cell sequencing and the integration of ATAC-seq and RNA-seq data, learning such complex mechanisms from limited independent data points still presents a daunting challenge, impeding GRN inference accuracy. To overcome this challenge, we present LINGER (LIfelong neural Network for GEne Regulation), a novel deep learning-based method to infer GRNs from single-cell multiome data with paired gene expression and chromatin accessibility data from the same cell. LINGER incorporates both 1) atlas-scale external bulk data across diverse cellular contexts and 2) the knowledge of transcription factor (TF) motif matching tocis-regulatory elements as a manifold regularization to address the challenge of limited data and extensive parameter space in GRN inference. Our results demonstrate that LINGER achieves 2-3 fold higher accuracy over existing methods. LINGER reveals a complex regulatory landscape of genome-wide association studies, enabling enhanced interpretation of disease-associated variants and genes. Additionally, following the GRN inference from a reference sc-multiome data, LINGER allows for the estimation of TF activity solely from bulk or single-cell gene expression data, leveraging the abundance of available gene expression data to identify driver regulators from case-control studies. Overall, LINGER provides a comprehensive tool for robust gene regulation inference from genomics data, empowering deeper insights into cellular mechanisms.
The genome ofLitomosoides sigmodontisilluminates the origins of Y chromosomes in filarial nematodes
Authors: Stevens Lewis , Kieninger Manuela , Chan Brian , Wood Jonathan M D , de la Rosa Pablo Gonzalez , Allen Judith , Blaxter Mark
Published: August 2023

Heteromorphic sex chromosomes are usually thought to have originated from a pair of autosomes that acquired a sex-determining locus and subsequently stopped recombining, leading to degeneration of the sex-limited chromosome. In contrast, in rhabditid nematodes, sex is determined by an X-chromosome counting mechanism and males are hemizygous for one or more X chromosomes (XX/X0). Some species of filarial nematodes, including important parasites of humans, have heteromorphic XX/XY systems. It has been assumed that sex is determined by a Y-linked locus in these species. However, karyotypic analyses suggested that filarial Y chromosomes are derived from the unfused autosome following an X-to-autosome fusion. Here, we generated a chromosome-level reference genome forLitomosoides sigmodontis, a filarial nematode with the ancestral filarial karyotype and sex determination mechanism (XX/X0). We mapped the assembled chromosomes to the rhabditid nematode ancestral linkage (or Nigon) elements. We found that theL. sigmodontisX chromosome was formed from a fusion of NigonX (the ancestrally X-linked element) and NigonD (ancestrally autosomal) that occurred in the last common ancestor of all filarial nematodes. In the two filarial lineages with XY systems, the X chromosomes were formed from two recent and independent fusions of the ancestral X chromosome with different autosomal Nigon elements. In both lineages, the region shared by the neo-X and neo-Y chromosomes is within the ancestrally autosomal portion of the X, confirming that the filarial Y chromosomes are derived from unfused autosomes. Sex determination in XY filarial nematodes therefore likely continues to operateviathe ancestral X-chromosome counting mechanism, rather thanviaa neo-Y-linked sex-determining locus.
DOCK2-deficiency causes defects in anti-viral T cell responses and poor control of herpes simplex virus infection
Authors: Randall Katrina L. , Flesch Inge E.A. , Mei Yan , Miosge Lisa A. , Aye Racheal , Yu Zhijia , Domaschenz Heather , Hollett Natasha A. , Russell Tiffany A. , Stefanovic Tijana , Wong Yik Chun , Goodnow Christopher C. , Bertram Edward M. , Enders Anselm , Tscharke David C.
Published: August 2023

The expanding number of rare immunodeficiency syndromes offers an opportunity to understand key genes that support immune defence against infectious diseases. However, patients with these diseases are by definition rare. In addition, any analysis is complicated by treatments and co-morbid infections requiring the use of mouse models for detailed investigations. Here we develop a mouse model of DOCK2 immunodeficiency and demonstrate that these mice have delayed clearance of herpes simplex virus type 1 (HSV-1) infections. Further, we found that they have a critical, cell intrinsic role of DOCK2 in the clonal expansion of anti-viral CD8+T cells despite normal early activation of these cells. Finally, while the major deficiency is in clonal expansion, the ability of primed and expanded DOCK2-deficient CD8+T cells to protect against HSV-1-infection is also compromised. These results provide a contributing cause for the frequent and devastating viral infections seen in DOCK2-deficient patients and improve our understanding of anti-viral CD8+T cell immunity.
Elucidating the Membrane Binding Process of a Disordered Protein: Dynamic Interplay of Anionic Lipids and the Polybasic Region
Authors: Alavizargar Azadeh , Gass Maximilian , Krahn Michael P. , Heuer Andreas
Published: August 2023

Intrinsically disordered regions of proteins are responsible for many biological processes such as in the case of liver kinase LKB1 – a serine/threonine kinase, relevant for cell proliferation and cell polarity. LKB1 itself becomes fully activated upon recruitment to the plasma membrane by binding of its disordered C-terminal polybasic motif consisting of eight lysines/arginines to phospholipids. Here we present extensive molecular dynamics (MD) simulations of the polybasic motif interacting with a model membrane composed of phosphatidylcholin (POPC) and phosphatidic acid (PA) and cell culture experiments. Protein-membrane binding effects are due to the electrostatic interactions between the polybasic amino acids and PAs. For significant binding the first three lysines turn out to be dispensable, which was also recapitulated in cell culture using transfected GFP-LKB1 variants. LKB1-membrane binding results in a non-monotonous changes in the structure of the protein as well as of the membrane, in particular accumulation of PAs and reduced thickness at the protein-membrane contact area. The protein-lipid binding turns out to be highly dynamic due to an interplay of PA-PA repulsion and protein-PA attraction. The thermodynamics of this interplay is captured by a statistical fluctuation model, which allows the estimation of both energies. Quantification of the significance of each polar amino acid in the polybasic provides detailed insights into the molecular mechanism of the protein-membrane binding of LKB1. These results can be likely transferred to other proteins, which interact by intrinsically disordered polybasic regions with anionic membranes.
Modeling Allosteric Mechanisms of Eukaryotic Type II Topoisomerases
Authors: Evoli Stefania , Kariyawasam Nilusha L. , Nitiss Karin C. , Nitiss John L. , Wereszczynski Jeff
Published: August 2023

Type II topoisomerases (TopoIIs) are essential enzymes involved in critical nuclear processes such as genome organization, chromosome segregation, and various DNA metabolic events. As large, homodimeric complexes, they undergo a complex ATPase cycle that regulates capturing and passing one DNA double-helix through a second, cleaved DNA molecule. To date, the molecular-level details of how information about the bound nucleotide state is transmitted over vast ranges in the TopoII complex, and how protein substitutions disrupt these mechanisms, remain largely unknown. Here, we conducted extensive molecular dynamics simulations of the yeast TopoII enzyme in multiple nucleotide-bound states and with various amino acid substitutions. Our results reveal remarkable flexibility in the ATPase domains on the sub-microsecond timescale, with dynamics modulated by the identity of the bound nucleotides and the presence of local and distant amino acid substitutions. We identified specific allosteric networks that transmit information as the complex progresses through the hydrolysis cycle that involve residues within the protein and the bound DNA molecule. Notably, amino acid substitutions weakened many of these pathways. Collectively, our findings provide crucial molecular-level insights into the control of the TopoII catalytic cycle through nucleotide binding and hydrolysis and shed light on how mutations may disrupt this process.
Social context and the evolution of delayed reproduction in birds
Authors: Taylor Liam U. , Uyeda Josef C. , Prum Richard O.
Published: August 2023

One puzzling feature of avian life histories is that individuals in many different lineages delay reproduction for several years after they finish growing. Intraspecific field studies suggest that various complex social contexts--such as cooperative breeding groups, nesting colonies, and display leks--result in delayed reproduction because they require forms of sociosexual development that extend beyond physical maturation. Here, we explicitly propose this hypothesis and use a full suite of phylogenetic comparative methods to test it, analyzing the evolution of age at first reproduction (AFR) in females and males across 963 species of birds. Phylogenetic regressions support increased AFR in colonial females and males, cooperatively breeding males, and lekking males. Continuous Ornstein-Uhlenbeck models support distinct evolutionary regimes with increased AFR for all of cooperative, colonial, and lekking lineages. Discrete hidden state Markov models suggest a net increase in delayed reproduction for social lineages, even when accounting for hidden state heterogeneity and the potential reverse influence of AFR on sociality. Our results support the hypothesis that the evolution of social contexts reshapes the dynamics of life history evolution in birds. Comparative analyses of even the most broadly generalizable characters, such as AFR, must reckon with unique, heterogeneous, historical events in the evolution of individual lineages.
A type VII secretion system toxin functioning as a biofilm-specific intercellular signal inBacillus subtilis
Authors: Kobayashi Kazuo
Published: August 2023

Biofilms are cooperative bacterial communities, in which diffusible signal-mediated quorum sensing coordinates the activities of member cells. However, limited diffusion in extracellular polymeric substance (EPS)-filled biofilms suggests existence of another intercellular signaling mechanism that is more adapted to the biofilm environment. Here, I demonstrate that theyfjAoperon ofBacillus subtilisencodes one such signaling mechanism. TheyfjAoperon was induced by the two-component system DegSU, which controls biofilm development. Deleting theyfjAoperon resulted in increased expression of DegSU-regulated genes under nutrient-rich conditions, hastening the onset of sporulation in biofilms. TheyfjAoperon encoded the type VII secretion system effector toxin YFJ in addition to its related proteins. YFJ toxin-mediated intercellular competition required EPS components which promote close cell-cell association, suggesting that the contact-dependent YFJ toxin system functions specifically in biofilms. The YFJ toxin also functioned as an intercellular signal that controlled the activity of DegSU. I propose that the YFJ toxin system is a biofilm-specific intercellular signaling mechanism that controls cell fate in biofilms in response to nutrient conditions and population size.
Body weight, gonadectomy, and other risk factors for diagnosis of osteoarthritis in companion dogs
Authors: Graves Jessica L , McKenzie Brennen A , Koch Zane , Naka Alexander , Spofford Nathaniel , Morrison JoAnn
Published: August 2023

OBJECTIVE

To evaluate age, sex, body weight, breed, neuter status, and age at neutering as risk factors for diagnosis of osteoarthritis in companion dogs

ANIMALS

Dogs seen as patients at Banfield Pet Hospital in the United States from 1998-2019 with a date of death in 2019. The final cohort consisted of 131,140 dogs.

METHODS

In this retrospective cohort study, Cox proportional hazard models were used to test for associations between osteoarthritis incidence and age at baseline, sex, maximum body weight, maximum body condition score, neuter status, and age at neutering. The same model was used to test these associations in 12 representative breeds, chosen based on breed weight and sample size.

RESULTS

Older age, higher adult body weight, gonadectomy, and younger age at gonadectomy were significantly associated with higher risks of osteoarthritis in the total cohort and in all 12 breeds evaluated. Higher body condition score and sex were also significantly associated with osteoarthritis but with minimal effect sizes in the overall cohort, and these risk factors were not consistently significant in all breeds tested.

CLINICAL RELEVANCE

These results will assist veterinarians in identifying dogs at higher risk for osteoarthritis and applying appropriate diagnostic, preventative, and treatment interventions. An understanding of potentially modifiable risk factors, such as body condition, and neutering, will support evidence-based discussions with dog owners about risk management in individual patients.
An unconventional mechanism of IL-1β secretion that requires Type I IFN in lupus monocytes
Authors: Caielli Simone , Balasubramanian Preetha , Rodriguez-Alcazar Juan , Balaji Uthra , Wan Zurong , Baisch Jeanine , Smitherman Cynthia , Walters Lynnette , Sparagana Paola , Nehar-Belaid Djamel , Marches Radu , Nassi Lorien , Stewart Katie , Fuller Julie , Banchereau Jacques F. , Gu Jinghua , Wright Tracey , Pascual Virginia
Published: August 2023

Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN1. Thus, defective removal of mitochondria from mature red blood cells (Mito+RBCs), a feature of SLE, contributes to IFN production by myeloid cells2. Here we identify blood monocytes (Mo) that have internalized RBCs and co-express IFN-stimulated genes (ISGs) and interleukin-1β (IL-1β) in SLE patients with active disease. We show that ISG expression requires the interaction between Mito+RBC-derived mitochondrial DNA (mtDNA) and cGAS, while IL-1β production entails Mito+RBC-derived mitochondrial RNA (mtRNA) triggering of RIG-I-like receptors (RLRs). This leads to the cytosolic release of Mo-derived mtDNA that activates the NLRP3 inflammasome. Importantly, IL-1β release depends on the IFN-inducible myxovirus resistant protein 1 (MxA), which enables the translocation of this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. Our study highlights a novel and synergistic pathway involving IFN and the NLRP3 inflammasome in SLE.
In vitroimpact of fluconazole on oral microbial communities, bacterial growth and biofilm formation
Authors: Dornelas-Figueira Louise Morais , Ricomini Filho Antônio Pedro , Junges Roger , Åmdal Heidi Aarø , Cury Altair Antoninha Del Bel , Petersen Fernanda Cristina
Published: August 2023

Anti-fungal agents are widely used to specifically eliminate infections by fungal pathogens. However, the specificity of anti-fungal agents has been challenged by a few studies demonstrating anti-bacterial inhibitory effects against Mycobateria and Streptomyces species. Here we evaluated for the first time the potential effect of fluconazole, the most clinically used antifungal agent, on a human oral microbiota biofilm model. The results showed that biofilm viability on blood and mitis-salivarius agar media was progressively increased in the presence of fluconazole at clinically relevant concentrations, despite of a reduction in biomass. Target PCR revealed higher proportions ofVeillonella atypica, Veillonella disparandLactobacillusspp. in the fluconazole treated samples compared to the control, whileFusobacterium nucleatumwas reduced andStreptococcusspp was not significantly affected. Further, we tested the potential impact of fluconazole using single-species models. Our results usingStreptococcus mutansandStreptococcus mitisluciferase reporters showed thatS. mutansplanktonic growth was not significantly affected by fluconazole, while forS, mitisplanktonic growth, but not biofilm viability, was inhibited at the highest concentration. Fluconazole effects onS. mitisbiofilm biomass were concentration and time-dependent. Exposure for 48h to the highest concentration of fluconazole was associated withS. mitisbiofilms with the most increased biomass. Potential growth inhibitory effects were further tested using four non-streptococcal species. Among these, planktonic growth of bothEscherichia coliandGranulicatella adiacenswere inhibited by fluconazole. Conclusions: The data indicate bacterial responses to fluconazole that extend to a broader range of bacterial species than previously anticipated from the literature, with the potential to disturb microbial biofilm communities. Future studies are warranted to further identify the breath of species for which growth may be impacted by anti-fungal agents, and possible mechanisms involved.
Gbx2 controls amacrine cell dendrite stratification through Robo1/2 receptors
Authors: Kerstein Patrick C. , Agreda Yessica Santana , Curran Bridget M. , Ma Le , Wright Kevin M.
Published: August 2023

Within the neuronal classes of the retina, amacrine cells (ACs) exhibit the greatest neuronal diversity in morphology and function. We show that the selective expression of the transcription factorGbx2is required for cell fate specification and dendritic stratification of an individual AC subtype in the mouse retina. We identify Robo1 and Robo2 as downstream effectors that when deleted, phenocopy the dendritic misprojections seen inGbx2mutants. Slit1 and Slit2, the ligands of Robo receptors, are localized to the OFF layers of the inner plexiform layer where we observe the dendritic misprojections in bothGbx2andRobo1/2mutants. We show that Robo receptors also are required for the proper dendritic stratification of additional AC subtypes, such as Vglut3+ ACs. These results show both that Gbx2 functions as a terminal selector in a single AC subtype and identify Slit-Robo signaling as a developmental mechanism for ON-OFF pathway segregation in the retina.
Ice nucleation proteins self-assemble into large fibres to trigger freezing at near 0 °C
Authors: Hansen Thomas , Lee Jocelyn C. , Reicher Naama , Ovadia Gil , Guo Shuaiqi , Guo Wangbiao , Liu Jun , Braslavsky Ido , Rudich Yinon , Davies Peter L.
Published: August 2023

In nature, frost can form at a few degrees below 0 °C. However, this process requires the assembly of tens of thousands of ice-like water molecules that align together to initiate freezing at these relatively high temperatures. Water ordering on this scale is mediated by the ice nucleation proteins of common environmental bacteria likePseudomonas syringaeandP. borealis. However, individually, these 100-kDa proteins are too small to organize enough water molecules for frost formation, and it is not known how giant, megadalton-sized multimers, which are crucial for ice nucleation at high sub-zero temperatures, form. The ability of multimers to self-assemble was suggested when the transfer of an ice nucleation protein gene intoEscherichia coliled to efficient ice nucleation. Here we demonstrate that a positively-charged sub-domain at the C-terminal end of the central beta-solenoid of the ice nucleation protein is crucial for multimerization. Truncation, relocation, or change of the charge of this subdomain caused a catastrophic loss of ice nucleation ability. Cryo-electron tomography of the recombinantE. colishowed that the ice nucleation protein multimers form fibres that are ∼ 5 nm across and up to 200 nm long. A model of these fibres as an overlapping series of antiparallel dimers can account for all their known properties and suggests a route to making cell-free ice nucleators for biotechnological applications.
Positive feedback regulation ofPparγ1svandPparγ2during adipogenesis in 3T3-L1 cells
Authors: Takenaka Yasuhiro , Kakinuma Yoshihiko , Inoue Ikuo
Published: August 2023

We have previously identified the novel splicing variant of mousePparγ(Pparγ1sv) and proposed the synergistic regulation of the early stage of adipocyte differentiation byPparγ1svandPparγ2. Here, we report the finding of PPARγ-binding sites within thePparγgene locus and its importance in adipogenesis and propose the positive feedback regulation ofPparγ1svandPparγ2expression during the adipocyte differentiation of 3T3-L1 cells.
Curved crease origami and topological singularities at a cellular scale enable hyper-extensibility ofLacrymaria olor
Authors: Flaum Eliott , Prakash Manu
Published: August 2023

Eukaryotic cells undergo dramatic morphological changes during cell division, phagocytosis and motility. Fundamental limits of cellular morphodynamics such as how fast or how much cellular shapes can change without harm to a living cell remain poorly understood. Here we describe hyper-extensibility in the single-celled protistLacrymaria olor, a 40µm cell which is capable of reversible and repeatable extensions (neck-like protrusions) up to 1500µm in 30 seconds. We discover that a unique and intricate organization of cortical cytoskeleton and membrane enables these hyper-extensions that can be described as the first cellular scale curved crease origami. Furthermore, we show how these topological singularities including d- cones and twisted domain walls provide a geometrical control mechanism for the deployment of membrane and microtubule sheets as they repeatably spool thousands of time from the cell body. We lastly build physical origami models to understand how these topological singularities provide a mechanism for the cell to control the hyper-extensile deployable structure. This new geometrical motif where a cell employs curved crease origami to perform a physiological function has wide ranging implications in understanding cellular morphodynamics and direct applications in deployable micro-robotics.

Significance statement

Here we present the discovery of curved crease origami at the scale of a single cell. We show how topological singularities in the origami (d-cones) and twist walls in microtubule ribbons control deployment of a hyper-extensile neck in a single-celled protist. Our work establishes a direct link between geometry and cell behavior, connecting form and function of cellular morphodynamics.
Bronchoconstriction damages airway epithelia by excess crowding-induced extrusion
Authors: Bagley Dustin C. , Russell Tobias , Ortiz-Zapater Elena , Fox Kristina , Redd Polly F. , Joseph Merry , Deering-Rice Cassandra , Reilly Christopher , Parsons Maddy , Rosenblatt Jody
Published: August 2023

Asthma is deemed an inflammatory disease, yet the defining diagnostic symptom is mechanical bronchoconstriction. We previously discovered a conserved process that drives homeostatic epithelial cell death in response to mechanical cell crowding called cell extrusion(1, 2). Here, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion. While relaxing airways with the rescue treatment albuterol did not impact these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these symptoms. Our findings propose a new etiology for asthma, dependent on the mechanical crowding of a bronchoconstrictive attack. Our studies suggest that blocking epithelial extrusion, instead of ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.
Rapid and unbiased enrichment of extracellular vesicles via meticulously engineered peptide
Authors: Wang Le , Gong Zhou , Wang Ming , Liang Yi-Zhong , Zhao Jing , Xie Qi , Wu Xiao-Wei , Li Qin-Ying , Zhang Cong , Ma Li-Yun , Zheng Si-Yang , Jiang Ming , Yu Xu , Xu Li
Published: August 2023

Extracellular vesicles (EVs) have garnered significant attention in biomedical applications, particularly as biomarkers and therapeutic agents for cancer diagnosis and treatment. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance concentration in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the rapid isolation of EVs in 20 min with ∼ 80% recovery. By inserting the peptide into the phospholipid bilayer of EVs, our method enables the unbiased isolation of EVs. Moreover, our approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, we show that the isolated EVs could be directly applied for downstream protein and nucleic acids analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of EGFR and KRAS gene mutation in clinical plasma samples. Our approach offers new possibilities for utilizing EVs in cancer diagnostics through liquid biopsy, as well as in various other biomedical applications.
RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis
Authors: Quiroz Erik J. , Kim Seongjae , Gautam Lalit K. , Borok Zea , Kintner Christopher , Ryan Amy L.
Published: August 2023

A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance.
Poly[[[μ3-3-(2-carboxylatophenyl)propionato][μ2-N,N′-(ethane-1,2-diyl)bis(pyridine-4-carboxamide)]copper(II)] monohydrate], a layered coordination polymer with (4,4) topology
Authors: Gaskin Gabrielle J. , LaDuca Robert L.
Published: August 2023

In the title compound, {[Cu(C10H8O4)(C14H14N4O2)]·H2O}
n
, the CuII cations are coordinated in a square-pyramidal fashion, with trans pyridyl-N donor atoms from two N-(2-(pyridin-3-ylamino)ethyl)isonicotinamide (pein) ligands in the basal plane. The other three coordination sites are taken up by carboxylate O-atom donors from three different 3-(2-carboxyphenyl)propionate (cpp) ligands. The central ethylenediamine segments of the pein ligands are disordered equally over two sets of positions. {Cu2O2} rhomboid clusters are connected into [Cu(cpp)(pein)]
n
(4,4) coordination polymer grids by the full span of the cpp and pein ligands. Individual layer motifs stack in an AAA pattern along the a axis by means of interlayer hydrogen-bonding interactions.
Unlocking the gender diversity–group performance link: the moderating role of relative cultural distance
Authors: Andrieu Guillaume , Montani Francesco , Setti Ilaria , Sommovigo Valentina
Published: August 2023

Purpose

This study aims to shed light on the relationship between gender diversity and group performance by considering the moderating role of relative cultural distance. Drawing from the categorization–elaboration model (CEM), the authors hypothesize that gender-diverse collaborative learning groups perform better when a low level of relative cultural distance in country-level individualism–collectivism or power distance exists among group members.

Design/methodology/approach

To test this hypothesis, the authors conducted a study on 539 undergraduate students organized into 94 groups. The assessment of group performance was based on scores given by external raters.

Findings

The authors found that relative cultural distance significantly moderated the gender diversity–group performance relationship such that gender diversity was positively related to group performance when the collaborative learning group included members who similarly valued individualism–collectivism or power distance (i.e. relative cultural distance was low) and was negatively related to group performance when the collaborative learning group comprised members who differently valued individualism–collectivism or power distance (i.e. relative cultural distance was high).

Originality/value

This study contributes to understanding when gender diversity is positively associated with group performance by expanding the range of previously examined diversity dimensions to include relative cultural distance in country-level individualism–collectivism and power distance.
Market development of Islamic banking in Pakistan and its economic impact
Authors: Shaikh Salman Ahmed
Published: August 2023

Purpose

This study aims to examine the dynamics of the market development of Islamic banking in Pakistan. This study investigates how shocks to the economy in the form of changes in benchmark rate and exchange rate and internal factors such as efficiency, profitability and asset quality affect the development of Islamic banking. The study also evaluates the impact of Islamic banking on the real economy in the macro perspective and society at large in terms of inclusiveness, competitiveness and fairness.

Design/methodology/approach

Autoregressive distributed lagged model method is used for analysing the short-run and long-run determinants of market development of Islamic banking and the economic impact of Islamic banking on the real economy.

Findings

Profitability and exchange rate have a positive effect on market development of Islamic banking while higher inefficiency and interbank rate have a negative effect. On the other hand, financing intensity and profitability in Islamic banking positively affect the large-scale manufacturing sector.

Practical implications

Stable profits, high asset quality, efficiency and rising import demand with low policy rate environment complement Islamic banking growth. Moreover, the economic assessment shows that Islamic banks have been able to achieve the financial inclusion of those who want to avoid Riba, but they need concerted efforts to improve competitiveness and distinction with regard to distributional impact.

Originality/value

To the best of the authors’ knowledge, this is the first study in Pakistan to evaluate determinants of market development of Islamic banking taking 16-year quarterly data and assessing the economic effects of Islamic banking on inclusiveness, competitiveness and fairness.
How to program autonomous vehicle (AV) crash algorithms: an Islamic ethical perspective
Authors: Elmahjub Ezieddin , Qadir Junaid
Published: August 2023

Purpose

Fully autonomous self-driving cars not only hold the potential for significant economic and environmental advantages but also introduce complex ethical dilemmas. One of the highly debated issues, known as the “trolley problems,” revolves around determining the appropriate actions for a self-driving car when faced with an unavoidable crash. Currently, the discourse on autonomous vehicle (AV) crash algorithms is primarily shaped by Western ethical traditions, resulting in a Eurocentric bias due to the dominant economic and political influence of the West. However, considering that AV technology will be deployed across diverse cultural and religious contexts, this paper aims to contribute to the discourse by providing an Islamic perspective on programming the response of AVs in the event of an imminent crash.

Design/methodology/approach

This study proposes a novel methodology based on the Islamic concept of maṣlaḥa for the normative assessment of ethical decisions related to AV programming.

Findings

Drawing upon the works of classic Islamic jurists, this study highlights two distinct normative visions within Islamic traditions (akin to deontology and consequentialism) concerning the preservation of human lives in the context of AVs. This study explores the shared and divergent elements between Islamic and Western ethical approaches proposed for AVs.

Originality/value

This pioneering work examines AV crash algorithms from an Islamic perspective, filling a void in the global ethical discourse. This work will also serve an important role to bridge the gap between the theoretical Islamic ethical principles and their practical application in the realm of AVs.
Factors influencing initial public acceptance of integrating the ChatGPT-type model with government services
Authors: Yang Liu , Wang Jian
Published: August 2023

Purpose

Integrating the Chat Generative Pre-Trained Transformer-type (ChatGPT-type) model with government services has great development prospects. Applying this model improves service efficiency but has certain risks, thus having a dual impact on the public. For a responsible and democratic government, it is necessary to fully understand the factors influencing public acceptance and their causal relationships to truly encourage the public to accept and use government ChatGPT-type services.

Design/methodology/approach

This study used the Latent Dirichlet allocation (LDA) model to analyze comment texts and summarize 15 factors that affect public acceptance. Multiple-related matrices were established using the grey decision-making trial and evaluation laboratory (grey-DEMATEL) method to reveal causal relationships among factors. From the two opposite extraction rules of result priority and cause priority, the authors obtained an antagonistic topological model with comprehensive influence values using the total adversarial interpretive structure model (TAISM).

Findings

Fifteen factors were categorized in terms of cause and effect, and the antagonistic topological model with comprehensive influence values was also analyzed. The analysis showed that perceived risk, trust and meeting demand were the three most critical factors of public acceptance. Meanwhile, perceived risk and trust directly affected public acceptance and were affected by other factors. Supervision and accountability had the highest driving power and acted as the causal factor to influence other factors.

Originality/value

This study identified the factors affecting public acceptance of integrating the ChatGPT-type model with government services. It analyzed the relationship between the factors to provide a reference for decision-makers. This study introduced TAISM to form the LDA-grey-DEMATEL-TAISM method to provide an analytical paradigm for studying similar influencing factors.
Critical Junctures: Independence Movements and Democracy in Africa
Authors: García‐Ponce Omar , Wantchekon Leonard
Published: August 2023

We show that current levels of democracy in Africa are linked to the nature of its independence movements. Using different measures of political regimes and historical data on anticolonial movements, we find that countries that experienced rural insurgencies tend to have autocratic regimes, while those that faced urban protests tend to have more democratic institutions. The association between the type of independence movement and democracy is statistically significant for the post‐Cold War period and robust to a number of potential confounding factors and sensitivity checks. We provide evidence for causality in this relationship by using an instrumental variables approach and a difference‐in‐differences design with fixed effects. Furthermore, we adjudicate between two potential mechanisms and find support for a behavioral path dependence hypothesis. Urban protests enabled participants to develop norms of peaceful political behavior, which provided cultural bases for liberal democracy. In contrast, armed rebellions generated behavioral patterns that perpetuated political exclusion and the use of violence as a form of political dissent.
Topical corticosteroids inhibit allergic skin inflammation but are ineffective in impeding the formation and expansion of resident memory T cells
Authors: Ono Emi , Lenief Vanina , Lefevre Marine‐Alexia , Cuzin Roxane , Guironnet‐Paquet Aurélie , Mosnier Amandine , Nosbaum Audrey , Nicolas Jean‐Francois , Vocanson Marc
Published: August 2023

Background

Tissue‐resident memory T (TRM) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease.

Methods

We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal TRM cells in a preclinical model of ACD to 2,4‐dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ TRM by flow cytometry and RNA sequencing.

Results

The impact of TA on TRM formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of TRM upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of TRM. Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin TRM, but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific TRM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, TRM re‐expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications.

Conclusions

Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen‐specific TRM, which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis.
Do you ‘like’ problems? The linkage between college students' interactions with alcohol‐related content on social media and their alcohol‐related problems
Authors: Steers Mai‐Ly N. , Strowger Megan , Tanygin Angela B. , Ward Rose Marie
Published: August 2023

Introduction

Alcohol‐related content (ARC) on social media and drinking motives impact college students' drinking. Most studies have examined peer‐generated ARC on drinking outcomes but have yet to extend this relationship to other sources of influence. The current study explores the link between drinking motives, alcohol company ARC, celebrity ARC, and alcohol‐related problems among college students.

Methods

Students (N = 454) from two US universities completed a cross‐sectional online survey assessing demographics; drinking motives (Drinking Motives Questionnaire‐Revised; Cooper, Psychol Assess. 1994;6:117–28); following/awareness of alcohol company ARC; engagement with celebrity ARC; peak drinks (most drinks consumed on one occasion); and alcohol‐related problems (e.g., passed out).

Results

Greater celebrity ARC was linked to coping, enhancement, and conformity motives, and peak drinks. Frequent engagement with celebrity ARC was associated with higher problems. Positive indirect effects were observed from celebrity ARC to problems through coping and conformity motives, and peak drinks. After having adjusted for the influence of celebrity ARC, no significant pathways were found between alcohol company ARC and any of the drinking motives, peak drinks or problems, nor were there any indirect effects between alcohol company ARC and problems.

Discussion and Conclusions

Results revealed that a possible explanation for why students who engaged with celebrity ARC experience problems was due to coping and conformity motives as well as peak drinks. Interventions targeting alcohol cognitions might assess engagement with and exposure to different sources of ARC given their potential to influence problems.