bluuebunny/crossref_metadata_2025 huggingface dataset:
Super-Resolved FRET and Co-Tracking in pMINFLUX
Authors: Cole Fiona , Zähringer Jonas , Bohlen Johann , Schröder Tim , Steiner Florian , Stefani Fernando D. , Tinnefeld Philip
Published: March 2023

Single-molecule FRET (smFRET) is widely used to investigate dynamic (bio) molecular interactions taking place over distances of up to 10 nm. With the advent of recent super-resolution methods such as MINFLUX, MINSTED or RASTMIN, the spatiotemporal resolution of these techniques advanced towards the smFRET regime. While these methods do not suffer from the spatial restriction of FRET, they only visualize one emitter at a time, thus rendering fast dynamics of interactions out of reach. Here, we describe two approaches to overcome this limitation in pMINFLUX using its intrinsic fluorescence lifetime information. First, we combined pMINFLUX with smFRET. This enabled us to track a FRET donor fluorophore and simultaneously colocalize its FRET acceptor with nanometer precision. To extend co-localized tracking beyond the FRET range, we developed pMINFLUX lifetime multiplexing, a method to simultaneously track two fluorophores with similar spectral properties but distinct fluorescence lifetimes. We demonstrated its application on both static and dynamic DNA origami systems with a precision better than 2 nm. Within the FRET range, pMINFLUX lifetime multiplexing additionally uses a novel combined phasor-microtimegating approach. This paves the way for nanometer precise co-localized tracking for inter-dye distances between 4 nm and 100 nm, closing the resolution gap between smFRET and co-tracking.

Graphical Abstract
Primate TRIM34 is a broadly-acting, TRIM5-dependent lentiviral restriction factor
Authors: Twentyman Joy , Khalifeh Anthony , Felton Abby L. , Emerman Michael , OhAinle Molly
Published: March 2023

Human immunodeficiency virus (HIV) and other lentiviruses adapt to new hosts by evolving to evade host-specific innate immune proteins that differ in sequence and often viral recognition between host species. Understanding how these host antiviral proteins, called restriction factors, constrain lentivirus replication and transmission is key to understanding the emergence of pandemic viruses like HIV-1. Human TRIM34, a paralogue of the well-characterized lentiviral restriction factor TRIM5α, was previously identified by our lab via CRISPR-Cas9 screening as a restriction factor of certain HIV and SIV capsids. Here, we show that diverse primate TRIM34 orthologues from non-human primates can restrict a range of Simian Immunodeficiency Virus (SIV) capsids including SIVAGM-SAB, SIVAGM-TANand SIVMACcapsids, which infect sabaeus monkeys, tantalus monkeys, and rhesus macaques, respectively. All primate TRIM34 orthologues tested, regardless of species of origin, were able to restrict this same subset of viral capsids. However, in all cases, this restriction also required the presence of TRIM5α. We demonstrate that TRIM5α is necessary, but not sufficient, for restriction of these capsids, and that human TRIM5α functionally interacts with TRIM34 from different species. Finally, we find that both the TRIM5α SPRY v1 loop and the TRIM34 SPRY domain are essential for TRIM34-mediated restriction. These data support a model in which TRIM34 is a broadly-conserved primate lentiviral restriction factor that acts in tandem with TRIM5α, such that together, these proteins can restrict capsids that neither can restrict alone.
Inferring CpG methylation signatures accumulated along human history from genetic variation catalogs
Authors: Si Yichen , Zöllner Sebastian
Published: March 2023

Understanding the DNA methylation patterns in the human genome is a key step to decipher gene regulatory mechanisms and model mutation rate heterogeneity in the human genome. While methylation rates can be measured e.g. with bisulfite sequencing, such measures do not capture historical patterns. Here we present a new method, Methylation Hidden Markov Model (MHMM), to estimate the accumulated germline methylation signature in human population history leveraging two properties: (1) Mutation rates of cytosine to thymine transitions at methylated CG dinucleotides are orders of magnitude higher than that in the rest of the genome. (2) Methylation levels are locally correlated, so the allele frequencies of neighboring CpGs can be used jointly to estimate methylation status. We applied MHMM to allele frequencies from the TOPMed and the gnomAD genetic variation catalogs. Our estimates are consistent with whole genome bisulfite sequencing (WGBS) measured human germ cell methylation levels at 90% of CpG sites, but we also identified ∼ 442, 000 historically methylated CpG sites that could not be captured due to sample genetic variation, and inferred methylation status for ∼ 721, 000 CpG sites that were missing from WGBS. Hypo-methylated regions identified by combining our results with experimental measures are 1.7 times more likely to recover known active genomic regions than those identified by WGBS alone. Our estimated historical methylation status can be leveraged to enhance bioinformatic analysis of germline methylation such as annotating regulatory and inactivated genomic regions and provide insights in sequence evolution including predicting mutation constraint.
Clonal differences underlie variable responses to sequential and prolonged treatment
Authors: Schaff Dylan L. , Fasse Aria J. , White Phoebe E. , Vander Velde Robert J. , Shaffer Sydney M.
Published: March 2023

Cancer cells exhibit dramatic differences in gene expression at the single-cell level which can predict whether they become resistant to treatment. Treatment perpetuates this heterogeneity, resulting in a diversity of cell states among resistant clones. However, it remains unclear whether these differences lead to distinct responses when another treatment is applied or the same treatment is continued. In this study, we combined single-cell RNA-sequencing with barcoding to track resistant clones through prolonged and sequential treatments. We found that cells within the same clone have similar gene expression states after multiple rounds of treatment. Moreover, we demonstrated that individual clones have distinct and differing fates, including growth, survival, or death, when subjected to a second treatment or when the first treatment is continued. By identifying gene expression states that predict clone survival, this work provides a foundation for selecting optimal therapies that target the most aggressive resistant clones within a tumor.
The conserved protein CBA1 is required for vitamin B12uptake in different algal lineages
Authors: Sayer Andrew P. , Llavero-Pasquina Marcel , Geisler Katrin , Holzer Andre , Bunbury Freddy , Mendoza-Ochoa Gonzalo I. , Lawrence Andrew D. , Warren Martin J. , Mehrshahi Payam , Smith Alison G.
Published: March 2023

Microalgae play an essential role in global net primary productivity and global biogeochemical cycling, but despite their phototrophic lifestyle, over half of algal species depend on a supply of the corrinoid vitamin B12(cobalamin) for growth. This essential organic micronutrient is produced only by a subset of prokaryotic organisms, which implies that for algal species to use this compound, they must first acquire it from external sources. Previous studies have identified protein components involved in vitamin B12uptake in bacterial species and humans. However, little is known about how it is taken up in algae. Here, we demonstrate the essential role of a protein, CBA1 (for cobalamin acquisition protein 1), in B12uptake inPhaeodactylum tricornutum, using CRISPR-Cas9 to generate targeted knockouts, and inChlamydomonas reinhardtii, by insertional mutagenesis. In both cases, CBA1 knockout lines are no longer able to take up exogenous vitamin B12. Complementation of theC. reinhardtiimutants with the wildtypeCBA1gene restores B12uptake, and regulation ofCBA1expression via a riboswitch element can be used to control the phenotype. When visualised by confocal microscopy, a YFP-fusion withC. reinhardtiiCBA1 shows association with membranes. A bioinformatics analysis found that CBA1-like sequences are present in all the major eukaryotic phyla. Its presence is correlated with B12-dependent enzymes in many, although not all, taxa, suggesting CBA1 has a conserved role. Our results thus provide insight into the molecular basis of algal B12acquisition, a process that likely underpins many interactions in aquatic microbial communities.

One sentence summary

Knockout mutants and physiological studies demonstrate that the CBA1 protein is essential for uptake of vitamin B12in bothChlamydomonas reinhardtiiand the unrelatedPhaeodactylum tricornutum.
An open-source FACS automation system for high-throughput cell biology
Authors: Wiener Diane M. , Huynh Emily , Jeyakumar Ilakkiyan , Bax Sophie , Sama Samia , Cabrera Joana P. , Todorova Verina , Vangipuram Madhuri , Vaid Shivanshi , Otsuka Fumitaka , Sakai Yoshitsugu , Leonetti Manuel D. , Gómez-Sjöberg Rafael
Published: March 2023

Recent advances in gene editing are enabling the engineering of cells with an unprecedented level of scale. To capitalize on this opportunity, new methods are needed to accelerate the different steps required to manufacture and handle engineered cells. Here, we describe the development of an integrated software and hardware platform to automate Fluorescence-Activated Cell Sorting (FACS), a central step for the selection of cells displaying desired molecular attributes. Sorting large numbers of samples is laborious, and, to date, no automated system exists to sequentially manage FACS samples, likely owing to the need to tailor sorting conditions (“gating”) to each individual sample. Our platform is built around a commercial instrument and integrates the handling and transfer of samples to and from the instrument, autonomous control of the instrument’s software, and the algorithmic generation of sorting gates, resulting in walkaway functionality. Automation eliminates operator errors, standardizes gating conditions by eliminating operator-to-operator variations, and reduces hands-on labor by 93%. Moreover, our strategy for automating the operation of a commercial instrument control software in the absence of an Application Program Interface (API) exemplifies a universal solution for other instruments that lack an API. Our software and hardware designs are fully open-source and include step-by-step build documentation to contribute to a growing open ecosystem of tools for high-throughput cell biology.
Label-free observation of individual solution phase molecules
Authors: Needham Lisa-Maria , Saavedra Carlos , Rasch Julia K. , Sole-Barber Daniel , Schweitzer Beau S. , Fairhall Alex J. , Vollbrecht Cecilia H. , Mehlenbacher Brandon , Zhang Zhao , Tenbrake Lukas , Pfeifer Hannes , Chapman Edwin R. , Goldsmith Randall H.
Published: March 2023

The vast majority of chemistry and biology occurs in solution, and new label-free analytical techniques that can help resolve solution-phase complexity at the single-molecule level can provide new microscopic perspectives of unprecedented detail. Here, we use the increased light-molecule interactions in high-finesse fiber Fabry-Pérot microcavities to detect individual biomolecules as small as 1.2 kDa with signal-to-noise ratios >100, even as the molecules are freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of sub-populations in mixed samples. Strikingly, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight can also be resolved. Detection is based on a novel molecular velocity filtering and dynamic thermal priming mechanism leveraging both photo-thermal bistability and Pound-Drever-Hall cavity locking. This technology holds broad potential for applications in life and chemical sciences and represents a major advancement in label-freein vitrosingle-molecule techniques.
Clinical Evaluation of Post-Surgical Scar Hyperesthesia; an Exploratory Longitudinal Study
Authors: Kennedy Donna L. , Hettiaratchy Shehan , Alexander Caroline M.
Published: March 2023

Evidence for the objective clinical evaluation of scar hyperesthesia is lacking. This exploratory study investigated the clinical relevance and responsiveness of objective scar evaluation measures in adults following hand surgery.

With ethical approval and consent, participants were enrolled from one NHS hospital. Patient reported and investigator completed scar morphology, cosmesis, pain and function were evaluated at 1- and 4-months post-surgery. Statistical analysis investigated the responsiveness of outcome measures and association of physical measures with the Palmar Pain Severity Scale (PPS).

21 participants enrolled prior to premature study closure due to the COVID-19 pandemic; 13 completed follow up. Scar pain (p=.002); scar interference (PPI [p=.009]) and Brief Pain Inventory (BPI) scores (p=.03) improved. Neuropathic Pain Symptom Inventory (NPSI) scores demonstrated heterogeneity in scar pain; evoked pain predominated. Patient Scar Assessment Questionnaire (PSAQ) indicated improvement in cosmetic dissatisfaction and consciousness (p=.03; p=.003), respectively. Baseline psychological screening scores correlated with scar pain (p=.04), and interference (p< .001). Scar morphology, pliability and inflammation were not associated with scar pain. Significant differences in scar mechanical pain sensitivity (p=.04) and cold pain threshold (p=.05) were identified.

PPS and PPI scores were responsive in a heterogeneous hand surgery sample. BPI ‘worst pain’ identified severe pain, suggesting composite scar pain scores are required. The PSAQ robustly measured scar appearance and consciousness. Psychophysical tests of mechanical and thermal sensitivity are potential candidate objective measures of scar hyperesthesia. The NPSI demonstrates clinical utility for exploring scar pain symptoms and may support the elucidation of the drivers of persistent scar pain.
Reframing dopamine: Controlling the controller at the limbic-motor interface
Authors: Lloyd Kevin , Dayan Peter
Published: March 2023

Pavlovian influences notoriously interfere with operant behaviour; various such may be associated with the release of the neuromodulator dopamine in the nucleus accumbens. One role for cognitive control is suppressing these influences. Here, using the examples of active avoidance and omission behaviour, we examine the possibility that one instrument of control is direct manipulation of the dopamine signal itself.
Gut-associated functions are favored during microbiome assembly acrossC. eleganslife
Authors: Zimmermann Johannes , Piecyk Agnes , Sieber Michael , Petersen Carola , Johnke Julia , Moitinho-Silva Lucas , Künzel Sven , Bluhm Lena , Traulsen Arne , Kaleta Christoph , Schulenburg Hinrich
Published: March 2023

The microbiome expresses a variety of functions that influence host biology. The range of functions depends on composition of the microbiome, which itself can change during the lifetime of the host as a consequence of neutral assembly processes, host-mediated selection, and/or environmental conditions. To date, the exact dynamics of microbiome assembly, the underlying determinants as well as the resulting effects on host-associated functions are not always well understood. Here, we used the nematodeCaenorhabditis elegansand a defined community of fully sequenced, naturally associated bacteria to study microbiome dynamics and functions across the lifetime of individual hosts under controlled experimental conditions. By applying the neutral and null models, we demonstrate that bacterial community composition initially shows strongly declining levels of stochasticity, which, however, increase during late worm life, suggesting the action of random assembly processes in aged hosts following first colonization ofC. elegans. The adult microbiome is enriched in strains of the generaOchrobactrumandEnterobacterin comparison to the direct substrate and a host-free control environment. Using pathway analysis, metabolic, and ecological modelling, we further found that the lifetime assembly dynamics lead to an increase in gut-associated functions in the host-associated microbiome, possibly indicating that the initially colonizing bacteria are beneficial for the worm. Overall, our study introduces a framework for studying microbiome assembly dynamics based on the stochastic models and inference of functions, yielding new insights into the processes determining host-associated microbiome composition and function.

Importance

The microbiome plays a crucial role in host biology, with its functions depending on microbiome composition that can change during a host’s lifetime. To date, the dynamics of microbiome assembly and the resulting functions are not well understood. This study introduces a new approach to characterize the functional consequences of microbiome assembly by modelling both, the relevance of stochastic processes and metabolic characteristics of microbial community changes. The approach was applied to experimental time series data, obtained for the microbiome of the nematodeCaenorhabditis elegans. The results revealed significant differences in host-associated and environmental microbiomes. Stochastic processes only played a minor role, and the host showed an increase in beneficial bacteria and an enrichment of gut-associated functions, possibly indicating that the host actively shapes composition of its microbiome. Overall, this study provides a framework for studying microbiome assembly dynamics and yields new insights intoC. elegansmicrobiome functions.
Modulation of Pore Opening of Eukaryotic Sodium Channels by π-helices in S6
Authors: Choudhury Koushik , Delemotte Lucie
Published: March 2023

Voltage-gated sodium channels are heterotetrameric sodium selective ion channels that play a central role in electrical signaling in excitable cells. With recent advances in structural biology, structures of eukaryotic sodium channels have been captured in several distinct conformations corresponding to different functional states. The secondary structure of the pore lining S6 helices of subunit DI, DII, and DIV has been captured with both short π-helix stretches and in fully α-helical conformations. The relevance of these secondary structure elements for pore gating is not yet understood. Here, we propose that a π helix in at least DI-S6, DIII-S6, and DIV-S6 results in a fully conductive state. On the other hand, the absence of π-helix in either DI-S6 or DIV-S6 yields a sub-conductance state, and its absence from both DI-S6 and DIV-S6 yields a non-conducting state. This work highlights the impact of the presence of a π-helix in the different S6 helices of an expanded pore on pore conductance, thus opening new doors towards reconstructing the entire conformational landscape along the functional cycle of Nav Channels and paving the way to the design of state-dependent modulators.

Graphical Abstract
Autism is Associated within vivoChanges in Gray Matter Neurite Architecture
Authors: Christensen Zachary P. , Freedman Edward G. , Foxe John J.
Published: March 2023

Postmortem investigations in autism have identified anomalies in neural cytoarchitecture across limbic, cerebellar, and neocortical networks. These anomalies include narrow cell mini-columns and variable neuron density. However, difficulty obtaining sufficient post-mortem samples has often prevented investigations from converging on reproducible measures. Recent advances in processing magnetic resonance diffusion weighted images (DWI) makein vivocharacterization of neuronal cytoarchitecture a potential alternative to post-mortem studies. Using extensive DWI data from the Adolescent Brain Cognitive Developmentsm(ABCD®) study 142 individuals with an Autism diagnosis were compared with 8971 controls using a restriction spectrum imaging (RSI) framework that characterized total neurite density (TND), its component restricted normalized directional diffusion (RND), and restricted normalized isotropic diffusion (RNI). A significant decrease in TND was observed in Autism in the right cerebellar cortex (β=-0.005, SE =0.0015, p=0.0267), with significant decreases in RNI and significant increases in RND found diffusely throughout posterior and anterior aspects of the brain, respectively. Furthermore, these regions remained significant inpost-hocanalysis when the ASD sample was compared against a subset of 1404 individuals with other psychiatric conditions (pulled from the original 8971). These findings highlight the importance of characterizing neuron cytoarchitecture in Autism and the significance of their incorporation as physiological covariates in future studies.

Lay abstract

Children with autism have differences in neuron structure unique from the general populationandpopulations with attention, anxiety, and depression disorders. Brain imaging data on over 11,000 children was acquired at ages 9 and 11 years-of-age. Estimates of neuron density were derived from brain imaging data using recently validated techniques and comparative groups were composed using parent reported diagnosis of autism and other common psychiatric disorders. Consistent macro-structural changes in brain have been difficult to replicate and micro-structural changes have been historically difficult to acquire with other methodologies. We identified regional differences in the density of neuron cell bodies, neuron branching, and total neuron density in those with a reported diagnosis of ASD. Findings were consistent when compared against those with other psychiatric disorders in post-hoc analysis. These findings demonstrate the viability and importance of investigatingin vivochanges to neurons in those with autism to advance our current understanding of related physiology.
Likelihood-ratio test statistic for the finite-sample case in nonlinear ordinary differential equation models
Authors: Tönsing Christian , Steiert Bernhard , Timmer Jens , Kreutz Clemens
Published: March 2023

Likelihood ratios are frequently utilized as basis for statistical tests, for model selection criteria and for assessing parameter and prediction uncertainties, e.g. using the profile likelihood. However, translating these likelihood ratios into p-values or confidence intervals requires the exact form of the test statistic’s distribution. The lack of knowledge about this distribution for nonlinear ordinary differential equation (ODE) models requires an approximation which assumes the so-called asymptotic setting, i.e. a sufficiently large amount of data. Since the amount of data from quantitative molecular biology is typically limited in applications, this finite-sample case regularly occurs for mechanistic models of dynamical systems, e.g. biochemical reaction networks or infectious disease models. Thus, it is unclear whether the standard approach of using statistical thresholds derived for the asymptotic large-sample setting in realistic applications results in valid conclusions. In this study, empirical likelihood ratios for parameters from 19 published nonlinear ODE benchmark models are investigated using a resampling approach for the original data designs. Their distributions are compared to the asymptotic approximation and statistical thresholds are checked for conservativeness. It turns out, that corrections of the likelihood ratios in such finite-sample applications are required in order to avoid anti-conservative results.

Author summary

Statistical methods based on the likelihood ratio are ubiquitous in mathematical modelling in systems biology. For example confidence intervals of estimated parameters rely on the statistical properties of the likelihood-ratio test. However, it is often overlooked that these intervals sizes rely on assumptions on the amounts of data, which are regularly violated in typical applications in systems biology. By checking the appropriateness of these assumptions in models from the literature, this study shows that in a surprisingly large fraction confidence intervals might be too small. Using a geometric interpretation of parameter estimation in the so-called data space, it is motivated why these issues appear and how they depend on the identifiability of the model parameters. In order to avoid such problematic situations, this work makes suggestions on how to adapt the statistical threshold values for likelihood-ratio test. By this, it can be assured that valid statistical conclusions are drawn from the analysis, also in situations where only smaller data sets are available. Such corrections yield for example more conservative confidence interval sizes and thus decrease a potential underestimation of the parameter uncertainty.
Integrated Drivers of Basal and Acute Immunity in Diverse Human Populations
Authors: Souquette Aisha , Allen E. Kaitlynn , Oshansky Christine M. , Tang Li , Wong Sook-san , Jeevan Trushar , Shi Lei , Pounds Stanley , Elias George , Kuan Guillermina , Balmaseda Angel , Zapata Raul , Shaw-Saliba Kathryn , Damme Pierre Van , Tendeloo Viggo Van , Dib Juan Carlos , Ogunjimi Benson , Webby Richard , Schultz-Cherry Stacey , Pekosz Andrew , Rothman Richard , Gordon Aubree , Thomas Paul G.
Published: March 2023

Prior studies have identified genetic, infectious, and biological associations with immune competence and disease severity; however, there have been few integrative analyses of these factors and study populations are often limited in demographic diversity. Utilizing samples from 1,705 individuals in 5 countries, we examined putative determinants of immunity, including: single nucleotide polymorphisms, ancestry informative markers, herpesvirus status, age, and sex. In healthy subjects, we found significant differences in cytokine levels, leukocyte phenotypes, and gene expression. Transcriptional responses also varied by cohort, and the most significant determinant was ancestry. In influenza infected subjects, we found two disease severity immunophenotypes, largely driven by age. Additionally, cytokine regression models show each determinant differentially contributes to acute immune variation, with unique and interactive, location-specific herpesvirus effects. These results provide novel insight into the scope of immune heterogeneity across diverse populations, the integrative effects of factors which drive it, and the consequences for illness outcomes.
Multiple mechanisms of self-association of chemokine receptors CXCR4 and CCR5 demonstrated by deep mutagenesis
Authors: Gill Kevin S. , Mehta Kritika , Heredia Jeremiah D. , Krishnamurthy Vishnu V. , Zhang Kai , Procko Erik
Published: March 2023

Chemokine receptors are members of the rhodopsin-like class A GPCRs whose signaling through G proteins drives the directional movement of cells in response to a chemokine gradient. Chemokine receptors CXCR4 and CCR5 have been extensively studied due to their roles in white blood cell development and inflammation and their status as coreceptors for HIV-1 infection, among other functions. Both receptors form dimers or oligomers but the function/s of self-associations are unclear. While CXCR4 has been crystallized in a dimeric arrangement, available atomic resolution structures of CCR5 are monomeric. To investigate the dimerization interfaces of these chemokine receptors, we used a bimolecular fluorescence complementation (BiFC)-based screen and deep mutational scanning to find mutations that modify receptor self-association. Many disruptive mutations promoted self-associations nonspecifically, suggesting they aggregated in the membrane. A mutationally intolerant region was found on CXCR4 that matched the crystallographic dimer interface, supporting this dimeric arrangement in living cells. A mutationally intolerant region was also observed on the surface of CCR5 by transmembrane helices 3 and 4. Mutations from the deep mutational scan that reduce BiFC were validated and were localized in the transmembrane domains as well as the C-terminal cytoplasmic tails where they reduced lipid microdomain localization. The reduced self-association mutants of CXCR4 had increased binding to the ligand CXCL12 but diminished calcium signaling. There was no change in syncytia formation with cells expressing HIV-1 Env. The data highlight that multiple mechanisms are involved in self-association of chemokine receptor chains.
Oxidation-sensitive cysteines drive IL-38 amyloid formation
Authors: Diaz-Barreiro Alejandro , Cereghetti Gea , Tonacini Jenna , Talabot-Ayer Dominique , Kieffer-Jaquinod Sylvie , Huard Arnaud , Swale Christopher , Couté Yohann , Peter Matthias , Francés-Monerris Antonio , Palmer Gaby
Published: March 2023

Cytokines of the interleukin (IL)-1 family are widely expressed in epithelial surfaces, including the epidermis, where they play a key role in the maintenance of barrier integrity and host defense. A recent report associated the IL-1 family member IL-33 with stress granules (SGs) in epithelial cells. Formation of SGs is promoted by the aggregation of proteins harboring low complexity regions (LCRs). In this study, using computational analyses, we predicted the presence of LCRs in six of the eleven IL-1 family members. Among these, IL-38 contained a long LCR and localized to Ras GTPase-activating protein binding protein 1 (G3BP1) positive SGs, as well as to G3BP1 negative intracellular protein condensates in keratinocytes exposed to oxidative stress (OS). In addition, we identified two highly aggregation-prone amyloid core (AC) motifs in the IL-38 LCR and detected the formation of amyloid IL-38 aggregates in response to OS in cells andin vitro. Disulfide bond mapping,in silicomodelling and the analysis of specific cysteine mutants supported a model in which specific oxidation-sensitive cysteines act as redox switches to modify the conformation of IL-38 and thus the surface exposure of its ACs, shuttling it from a soluble state into biomolecular condensates. Finally, the presence of IL-38 granules in human epidermal layers highly exposed to environmental OS suggests that oxidation-induced formation of amyloid aggregates, as a previously unrecognized intrinsic biological property of IL-38, may be physiologically relevant at this epithelial barrier.
Machine learning-based estimation of spatial gene expression pattern during ESC-derived retinal organoid development
Authors: Fujimura Yuki , Sakai Itsuki , Shioka Itsuki , Takata Nozomu , Hashimoto Atsushi , Funatomi Takuya , Okuda Satoru
Published: March 2023

Organoids, which can reproduce the complex tissue structures found in embryos, are revolutionizing basic research and regenerative medicine. In order to use organoids for research and medicine, it is necessary to assess the composition and arrangement of cell types within the organoid, i.e., spatial gene expression. However, current methods are invasive and require gene editing and immunostaining. In this study, we developed a non-invasive estimation method of spatial gene expression patterns using machine learning. A deep learning model was trained with an encoder-decoder architecture on a dataset of retinal organoids derived from mouse embryonic stem cells. This method successfully estimated spatially plausible fluorescent patterns with appropriate intensities, enabling the non-invasive, quantitative estimation of spatial gene expression patterns within each tissue. Thus, this method could lead to new avenues for evaluating spatial gene expression patterns across a wide range of biology and medicine fields.

Highlights

A non-invasive estimation method of spatial gene expression pattern is proposed

A CNN architecture is employed to convert a phase-contrast to fluorescence image

The method was trained on a dataset of mouse ESC-derived retinal organoids

Spatially plausible patterns of Rx gene expressions were successfully estimated
Modelling contractile ring formation and division to daughter cells for simulating proliferative multicellular dynamics
Authors: Okuda Satoru , Hiraiwa Tetsuya
Published: March 2023

Cell proliferation is a fundamental process underlying embryogenesis, homeostasis, wound healing, and cancer. The process involves multiple events during each cell cycle, such as cell growth, contractile ring formation, and division to daughter cells, which affect the surrounding cell population geometrically and mechanically. However, existing methods do not comprehensively describe the dynamics of multicellular structures involving cell proliferation at a subcellular resolution. In this study, we present a novel model for proliferative multicellular dynamics at the subcellular level by building upon the nonconservative fluid membrane (NCF) model that we developed in earlier research. The NCF model utilizes a dynamically-rearranging closed triangular mesh to depict the shape of each cell, enabling us to analyze cell dynamics over extended periods beyond each cell cycle, during which cell surface components undergo dynamic turnover. The proposed model represents the process of cell proliferation by incorporating cell volume growth and contractile ring formation through an energy function and topologically dividing each cell at the cleavage furrow formed by the ring. Numerical simulations demonstrated that the model recapitulated the process of cell proliferation at subcellular resolution, including cell volume growth, cleavage furrow formation, and division to daughter cells. Further analyses suggested that the orientation of actomyosin stress in the contractile ring plays a crucial role in the cleavage furrow formation, i.e., circumferential orientation can form a cleavage furrow but isotropic orientation cannot. Furthermore, the model replicated tissue-scale multicellular dynamics, where the successive proliferation of adhesive cells led to the formation of a cell sheet and stratification on the substrate. Overall, the proposed model provides a basis for analyzing proliferative multicellular dynamics at subcellular resolution.
Grassroots accountability: the practical and symbolic aspects of performance
Authors: Millar John , Mueller Frank , Carter Chris
Published: March 2023

Purpose

The paper provides a theoretical framework for interdisciplinary accounting scholars interested in performances of accountability in front of live audiences.

Design/methodology/approach

This is a processual case study of “Falkirk in crisis” that covers the period from September 2021 to September 2022. The focus of this paper is two-fan-Q&A sessions held in October 2021 and June 2022. Both are naturally occurring discussions between two groups such as are found in previous research on routine events and accountability. This is a theoretically consequential case study.

Findings

A key insight of the paper is to identify the practical and symbolic dimensions of accountability. The paper demonstrates the need to align these two dimensions when responding to questions: a practical question demands a practical answer and a symbolic question requires a symbolic answer. Second, the paper argues that most fields contain conflicting logics and highlights that a complete performance of accountability needs to cover the different conflicting logics within the field. In this case, this means paying full attention to both the communitarian and results logics. A third finding is that a performance of accountability cannot succeed if the audience rejects attempts to impose an unpalatable definition of the situation. If these three conditions are not met, the performance is bound to fail.

Research limitations/implications

An important theoretical coontribution of the study is the application of Jeffery Alexander’s work on political performance to public performances of accountability.

Practical implications

The phenomenon explored in the paper (what the authors term “grassroots accountability”) has broad applicability to any situation in organizational or civic life where the power apex of an organization is required to engage with a group of informed and committed stakeholders – the “community”. For those who find themselves in the position of the fans in this study, the observations set out in the empirical narrative can serve as a useful practical guide. Attempts to answer a practical complaint with a symbolic answer (or vice versa) should be challenged as evasive.

Social implications

This paper studies an engagement of elite actors with ordinary (or grassroots) actors. The study shows important rules of engagement, including the importance of respecting the power of practical questions and the need to engage with these questions appropriately.

Originality/value

This paper offers a new vista for interdisciplinary accounting by synthesizing the accountability literature with the political performance literature. Specifically, the paper employs Jeffery Alexander’s work on practical and symbolic performance to study the microprocesses underpinning successful and unsuccessful performances of accountability.
Competition, risk-taking behavior and stability of commercial banks: evidence from Kenya
Authors: Wahinya Purity Wanjiru , Ondiba Rogers Ochenge , Kariuki Peter Wang’ombe
Published: March 2023

Purpose

This study analyzes the effects of competition and risk-taking behavior on the stability of commercial banks in Kenya.

Design/methodology/approach

An unbalanced panel dataset of 36 licensed commercial banks in Kenya for 2001–2020 was extracted from the published financial statements. A dynamic panel data analysis model, a two-step system generalized method of moments (GMM), was employed.

Findings

The results indicate that competition reinforces bank stability, whereas banks’ risk-taking behavior has an inverse relationship with strength.

Practical implications

The study confirms the competition-stability nexus, implying that measures may be implemented to foster competition among banks with reduced concentration. These measures may include, but are not limited to, reduced entry barriers and optimal capital requirements. Second, efforts should be made to ensure excessive risk-taking by banks. Employing an elaborate exposure monitoring system with clear warning signs is recommended.

Originality/value

This study is unique in several ways. First, it employs structural and nonstructural measures of competition and ex post standards of banks’ risk-taking behavior. Second, contrary to past studies, this study uses various firm-level measures of bank stability. Lastly, it provides essential empirical evidence from the context of a developing economy, whose institutional and macroeconomic environments differ significantly from those of a developed economy.
Consumer preferences for rice in East Africa
Authors: Twine Edgar Edwin , Ndindeng Sali Atanga , Mujawamariya Gaudiose , Adur-Okello Stella Everline , Kilongosi Celestine
Published: March 2023

Purpose

Improving the competitiveness of East Africa's rice industries necessitates increased and viable production of rice of the quality desired by consumers. This paper aims to understand consumer preferences for rice quality attributes in Uganda and Kenya to inform the countries' rice breeding programs and value chain development interventions.

Design/methodology/approach

Rice samples are obtained from retail markets in various districts/counties across the two countries. The samples are analyzed in a grain quality laboratory for the rice's physicochemical characteristics and the resulting data are used to non-parametrically estimate hedonic price functions. District/county dummies are included to account for potential heterogeneity in consumer preferences.

Findings

Ugandan consumers are willing to pay a price premium for rice with a relatively high proportion of intact grains, but the consumers discount chalkiness. Kenyan consumers discount high amylose content and impurities. There is evidence of heterogeneity in consumer preferences for rice in Mbale, Butaleja and Arua districts of Uganda and in Kericho and Busia counties of Kenya.

Originality/value

The study makes a novel contribution to the literature on consumer preferences for rice in East Africa by applying a hedonic pricing model to the data generated from a laboratory analysis of the physicochemical characteristics of rice samples obtained from the market. Rather than base our analysis on consumers' subjective sensory assessment of the quality characteristics of rice, standard laboratory methods are used to generate the data, which enables a more objective assessment of the relationship between market prices and the quantities of attributes present in the rice samples.
Generative artificial intelligence as a new context for management theories: analysis of ChatGPT
Authors: Korzynski Pawel , Mazurek Grzegorz , Altmann Andreas , Ejdys Joanna , Kazlauskaite Ruta , Paliszkiewicz Joanna , Wach Krzysztof , Ziemba Ewa
Published: March 2023

Purpose

The primary purpose of this paper is to examine how generative Artificial Intelligence (AI) such as ChatGPT may serve as a new context for management theories and concepts.

Design/methodology/approach

The paper presents the analyses of selected management theories on decision-making, knowledge management, customer service, human resource management and administrative tasks and explains what may change after generative AI adoption.

Findings

The paper indicates that some management theories and concepts need to be studied in the generative AI environment that may influence managerial work at the strategic, functional and administrative levels.

Research limitations/implications

This paper is an opinion piece article and does not refer to empirical data. It formulates some conclusions to further empirical research studies.

Originality/value

The paper analyzes selected management theories in a new technological setting. The paper also provides information about the functions of generative AI that are useful in understanding and overcoming how new technology may change organizations and management.
Getting the measure of the fourth industrial revolution: advantages and challenges of Industry 4.0 in the Turkish white goods industry
Authors: Şimşek Demirbağ Kübra , Yıldırım Nihan
Published: March 2023

Purpose

Industry 4.0 (I40) is an open window of opportunity for Turkey, a developed country, to eliminate technological dependence and produce with maximum productivity. However, I40, which corresponds to the fourth wave of industrial revolutions, brings both opportunities and challenges. In this context, this study aims to reveal the foresight of managers in the Turkish white goods industry (TWGI) regarding the advantages and challenges of I40 and compare them with the literature.

Design/methodology/approach

The Delphi method was used for the study. Data were collected from managers of companies that are members of the White Goods Suppliers Association (BEYSAD). Seventy managers from 55 companies participated in the first round, and 19 managers participated in the second round of Delphi.

Findings

The results show that the most frequently cited advantages are productivity/resource efficiency, data and information-enabled effectiveness/productivity, quality 4.0 and competitiveness/strategy. The most frequently mentioned challenges are financial resources/investment, employee qualification/training, technical/processual challenges and organizational transformation/leadership.

Research limitations/implications

The sample was limited to the managers of the TWGI.

Practical implications

Players in similar ecosystems and policymakers should consider the advantages and respond to potential challenges when creating roadmaps, taking the necessary steps and positioning themselves in the marketplace. In particular, the TWGI – Turkey’s showcase in international markets – should consider the undeniable benefits of the I40 transition to increase innovation.

Originality/value

The findings for the first time highlight the advantages and challenges of I40 in an industry in Turkey, and they will benefit the TWGI, which is among the leaders in Turkey in terms of digital maturity and innovation in its journey to I40.
Do SARS-CoV-2 hazards influence stakeholders? Evidence from a Polish seafood company
Authors: Wiśniewska Małgorzata Zdzisława , Grybek Tomasz
Published: March 2023

Purpose

The article presents the phenomenon of hazards related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the food supply chain (FSC) by identifying possible stakeholders of a seafood company who might be influenced by the hazards.

Design/methodology/approach

A case study analysis was conducted with a review of the organization's documentation alongside a semi-structured interview and an impact effort matrix.

Findings

Seven out of 18 stakeholders had to strongly engage in minimizing the effects of hazards related to SARS-CoV-2. The most important areas of cooperation regarded safety were identified. Both external and internal documents and reports regarding the minimizing of negative effects of hazards related to SARS-CoV-2 were required by institutional clients, official authorities and the studied organization itself. The proper identification of stakeholders and up-to-date knowledge about them allowed the organization to react faster and protect the FSC.

Research limitations/implications

The authors’ research was based on qualitative methods, so it lacked a diagnostic survey, along with similar studies for comparison of results and approaches.

Practical implications

The surveyed company may be a good benchmark for others to follow when choosing the appropriate approach in the field of stakeholder analysis for addressing new emerging risks.

Originality/value

The findings are important, timely and original, and they focus on a subject rarely studied in the literature. The information from the paper applies to numerous groups of food companies.
The effect of entrepreneurial education on entrepreneurial intention among master students: prior self-employment experience as a moderator
Authors: Le Trung Thanh , Nguyen Thanh Hieu , Ha Son Tung , Nguyen Quang Khai , Tran Nhat Minh , Duong Cong Doanh
Published: March 2023

Purpose

This article aims to draw a conceptual model that integrates the view from the entrepreneurial event model with entrepreneurial education and prior self-employment experience. The model tests the role of entrepreneurial education on the formation of intentions to become an entrepreneur and examines whether prior self-employed experiences moderate the route from entrepreneurial education, entrepreneurial perceived feasibility (PF) and perceived desirability (PD) into the entrepreneurial intention (EI).

Design/methodology/approach

The authors operated on a sample of 389 master's students by applying Cronbach's alpha, exploratory factor analysis, confirmatory factor analysis and structural equation modelling to illustrate the links between constructs.

Findings

The study found that entrepreneurial education is positively correlated with PF, PD, and intention to enter entrepreneurial activities. PD is determined as a partial mediator in the entrepreneurial education–intention link and full mediator in PF and EI. Moreover, the study revealed that prior self-employed experiences serve as a positive moderator in the path from entrepreneurial education and PD to EI.

Practical implications

The study offers several recommendations based on research findings so as to nurture and promote entrepreneurial activities among master's students.

Originality/value

The current research provides novel insights about the relationship between entrepreneurial education and intentions to become an entrepreneur over and about the central antecedents in the entrepreneurial event model and moderation effects of prior self-employed experiences.