bluuebunny/crossref_metadata_2025 huggingface dataset:
A multiscale theory for spreading and migration of adhesion-reinforced mesenchymal cells
Authors: Shu Wenya , Kaplan C. Nadir
Published: December 2023

We present a chemomechanical whole-cell theory for the spreading and migration dynamics of mesenchymal cells that can actively reinforce their adhesion to an underlying viscoelastic substrate as a function of its stiffness. Our multiscale model couples the adhesion reinforcement effect at the subcellular scale with the nonlinear mechanics of the nucleus–cytoskeletal network complex at the cellular scale to explain the concurrent monotonic area–stiffness and non-monotonic speed–stiffness relationships observed in experiments: we consider that large cell spreading on stiff substrates flattens the nucleus, increasing the viscous drag force on it. The resulting force balance dictates a reduction in the migration speed on stiff substrates. We also reproduce the experimental influence of the substrate viscosity on the cell spreading area and migration speed by elucidating how the viscosity may either maintain adhesion reinforcement or prevent it depending on the substrate stiffness. Additionally, our model captures the experimental directed migration behaviour of the adhesion-reinforced cells along a stiffness gradient, known as durotaxis, as well as up or down a viscosity gradient (viscotaxis or anti-viscotaxis), the cell moving towards an optimal viscosity in either case. Overall, our theory explains the intertwined mechanics of the cell spreading, migration speed and direction in the presence of the molecular adhesion reinforcement mechanism.
Uncovering loggerhead (
Caretta caretta
) navigation strategy in the open ocean through the consideration of their diving behaviour
Authors: Laforge Antoine , Gaspar Philippe , Barat Anne , Boyer Julien Temple , Candela Tony , Bourjea Jérôme , Ciccione Stéphane , Dalleau Mayeul , Ballorain Katia , Monsinjon Jonathan R. , Bousquet Olivier
Published: December 2023

While scientists have been monitoring the movements and diving behaviour of sea turtles using Argos platform terminal transmitters for decades, the precise navigational mechanisms used by these animals remain an open question. Until now, active swimming motion has been derived from total motion by subtracting surface or subsurface modelled ocean currents, following the approximation of a quasi-two-dimensional surface layer migration. This study, based on tracking and diving data collected from 25 late-juvenile loggerhead turtles released from Reunion Island during their pre-reproductive migration, demonstrates the importance of considering the subsurface presence of the animals. Using a piecewise constant heading model, we investigate navigation strategy using daily time-at-depth distributions and three-dimensional currents to calculate swimming velocity. Our results are consistent with a map and compass strategy in which swimming movements follow straight courses at a stable swimming speed (approx. 0.5 m s
−1
), intermittently segmented by course corrections. This strategy, previously hypothesized for post-nesting green and hawksbill turtles, had never been observed in juvenile loggerheads. These results confirm a common open-ocean navigation mechanism across ages and species and highlight the importance of considering diving behaviour in most studies of sea turtle spatial ecology.
Seasonality and the persistence of vector-borne pathogens
Authors: Khong Van Hai , Carmona Philippe , Gandon Sylvain
Published: December 2023

Many vector-borne diseases are affected by the seasonality of the environment. Yet, seasonality can act on distinct steps of the life cycle of the pathogen and it is often difficult to predict the influence of the periodic fluctuations of the environment on the basic reproduction ratio
R
0
of vector-borne pathogens. Here, we analyse a general vector-borne disease model and we account for periodic fluctuations of different components of the pathogen’s life cycle. We develop a perturbation analysis framework to obtain useful approximations to evaluate the overall consequences of seasonality on the
R
0
of the pathogen. This analysis reveals when seasonality is expected to increase or to decrease pathogen persistence. We show that seasonality in vector density or in the biting rate of the vector can have opposite effects on persistence and we provide a useful biological explanation for this result based on the covariance between key compartments of the epidemiological model. This framework could be readily extended to explore the influence of seasonality on other components of the life cycle of vector-borne pathogens.
LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians
Authors: Molina M. Dolores , Abduljabbar Dema , Guixeras Anna , Fraguas Susanna , Cebrià Francesc
Published: December 2023

Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial ‘LIM code’ to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in
Schmidtea mediterranea
. We found that
lim homeobox
(
lhx
) genes appear expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian, with some of them being co-expressed in the same cell types. We have identified that
Smed-islet1, -lhx1/5-1, -lhx2/9-3, -lhx6/8, -lmx1a/b-2
and -
lmx1a/b-3
are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while
Smed-lhx1/5.2
and
-lhx2/9.1
are required for the proper expression of intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in controlling axonal pathfinding (
lhx6/8
), axial patterning (
islet1
,
lhx1/5-1, lmx1a/b-3
), head/body proportions (
islet2
) and stem cell proliferation (
lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3
). Altogether, our results suggest that planarians might present a combinatorial LIM code that controls axial patterning and axonal growing and specifies distinct neuronal and intestinal cell identities.
Evaporation induced acoustic emissions in microfluidic vessels
Authors: Dutta S. , Bieling T. J. , Verbiest G. J.
Published: December 2023

Fluid flow processes such as drainage and evaporation in porous media are crucial in geological and biological systems. The motion of the displacement front of a moving fluid through multi-phase interfaces is often associated with abrupt mechanical energy release, detectable as acoustic emissions (AEs). The exact origin of these pulses and their damping mechanisms are still subjects of debate. Here, we study the characteristics of such AEs during evaporation of water from artificial microfluidic vessels, inspired by the physiology of vascular water-transport in plants. From the extracted settling times of the recorded AEs, we identify three pulse types and attribute their origins to bubble formation, snap-off events and rapid pore invasion. We also show that the resonance frequencies between 10 and 70 kHz present in specific pulse types decrease with increasing vessel radius (ranging from 0.25 to 1.0 mm) and length (ranging from 2.5 to 10.0 mm). Our findings provide insight into evaporation-induced AEs from microfluidic systems, and their potential use in non-invasive inspection or vascular health monitoring.
Evidence against egocentric prediction during language comprehension
Authors: Corps Ruth E. , Yang Fang , Pickering Martin J.
Published: December 2023

Although previous research has demonstrated that language comprehension can be egocentric, there is little evidence for egocentricity during prediction. In particular, comprehenders do not appear to predict egocentrically when the context makes it clear what the speaker is likely to refer to. But do comprehenders predict egocentrically when the context does not make it clear? We tested this hypothesis using a visual-world eye-tracking paradigm, in which participants heard sentences containing the gender-neutral pronoun
They
(e.g.
They would like to wear…
) while viewing four objects (e.g. tie, dress, drill, hairdryer). Two of these objects were plausible targets of the verb (tie and dress), and one was stereotypically compatible with the participant's gender (tie if the participant was male; dress if the participant was female). Participants rapidly fixated targets more than distractors, but there was no evidence that participants ever predicted egocentrically, fixating objects stereotypically compatible with their own gender. These findings suggest that participants do not fall back on their own egocentric perspective when predicting, even when they know that context does not make it clear what the speaker is likely to refer to.
Detection and Characterization of Microorganisms Linked to Unsealed drugs Sold in Ihiagwa Community, Owerri, Imo State
Authors: Ekeleme Uzochukwu Godswill , Ikwuagwu Vivian O. , Chukwuocha Uchechukwu , Nwakanma Jane , Adiruo Stephanie , Ogini Ikenna , Uche Ude Ifeoma
Published: December 2023

The contamination of pharmaceutical products by microorganisms poses a significant risk to public health. This study was conducted to detect and characterise microorganisms associated with unsealed drugs sold in Ihiagwa community in Owerri, Imo State. A variety of microbiological techniques were employed to analyze samples from unsealed drug containers. The identification process involved morphological, biochemical, and sugar utilisation methods, aiding in the accurate determination of microbial species. Microbial contamination was observed in 42 (84%) out of 50 samples, contaminants included bacteria and yeasts. The range of contamination is between 1.2 × 103 to 2.3 × 103 cfu/ml for viable count, 0.1 × 102 to 0.3 × 102 cfu/g for coliform count and 0.2 × 101 to 0.5 × 101 cfu/g. The identified microbes were Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. The most common bacterial isolate was Staphylococcus aureus (51.8%), while Candida albicans (73.3%) was the most prevalent fungi. The identification of potentially harmful microorganisms in these unsealed drug samples emphasize the importance of stringent quality control measures, improved handling, storage, and packaging practices to ensure product safety and efficacy especially among drug dealers.
miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity
Authors: Welle Theresa M. , Rajgor Dipen , Garcia Joshua D. , Kareemo Dean , Zych Sarah M. , Gookin Sara E. , Martinez Tyler P. , Dell’Acqua Mark L. , Ford Christopher P. , Kennedy Matthew J. , Smith Katharine R.
Published: December 2023

Activity-dependent protein synthesis is crucial for many long-lasting forms of synaptic plasticity. However, our understanding of the translational mechanisms controlling inhibitory synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the precise mechanisms controlling gephyrin translation during this process remain unknown. Here, we identify miR153 as a novel regulator ofGphnmRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting GABAergic synaptic structure and function. We find that iLTP induction downregulates miR153, reversing its translational suppression ofGphnmRNA and allowing for increasedde novogephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Overall, this work delineates a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.
Single cell sequencing as a general variant interpretation assay
Authors: Xu Hongxia , Chen Ling , Sun Mohan , Jean-Baptiste Ken , Cao Dan , Zhou Xingyan , Wong Sandy , Xiao Carmen , Liu Tong , Quijano Victor , Brandes Nadav , Germino Joe , Ntranos Vasilis , Ye Chun Jimmie , Aguet François , Farh Kyle Kai-How
Published: December 2023

The human genome contains ∼70 million possible protein-altering variants, the vast majority of which are of uncertain clinical significance. Closing this gap is essential for accurate diagnosis of disease-causing variants and understanding their mechanisms of action. Towards this goal, we developed a pooled perturbation approach combining saturation mutagenesis with single cell RNA sequencing to map the effects of every single nucleotide variant in a gene. We sequenced ∼440,000 cells expressing variants inCDKN2A(p16INK4a),TP53, andSOD1, observing almost all possible protein-coding variants, with a mean of 61 cells per variant. Using single cell gene expression signatures, we show that each gene may contain multiple types of pathogenic variants that affect distinct downstream pathways. We demonstrate that single cell expression signatures outperform existing bulk experimental assays and computational models for predicting pathogenicity, and summarize both the utility and potential limitations of single cell sequencing as a general variant interpretation assay.
Stochastic Epigenetic Mutations: Reliable Detection and Associations with Cardiovascular Aging
Authors: Markov Yaroslav , Levine Morgan , Higgins-Chen Albert T.
Published: December 2023

Stochastic Epigenetic Mutations (SEMs) have been proposed as novel aging biomarkers that have the potential to capture heterogeneity in age-related DNA methylation (DNAme) changes. SEMs are defined as outlier methylation patterns at cytosine-guanine dinucleotide (CpG) sites, categorized as hypermethylated (hyperSEM) or hypomethylated (hypoSEM) relative to a reference. While individual SEMs are rarely consistent across subjects, the SEM load – the total number of SEMs – increases with age. However, given poor technical reliability of measurement for many DNA methylation sites, we posited that many outliers might represent technical noise. Our study of whole blood samples from 36 individuals, each measured twice, found that 23.3% of hypoSEM and 45.6% hyperSEM are not shared between replicates. This diminishes the reliability of SEM loads, where intraclass correlation coefficients are 0.96 for hypoSEM and 0.90 for hyperSEM. We linked SEM reliability to multiple factors, including blood cell type composition, probe beta-value statistics, and presence of SNPs. A machine learning approach, leveraging these factors, filtered unreliable SEMs, enhancing reliability in a separate dataset of technical replicates from 128 individuals. Analysis of the Framingham Heart Study confirmed previously reported SEM association with mortality and revealed novel connections to cardiovascular disease. We discover that associations with aging outcomes are primarily driven by hypoSEMs at baseline methylated probes and hyperSEMs at baseline unmethylated probes, which are the same subsets that demonstrate highest technical reliability. These aging associations are preserved after filtering out unreliable SEMs and are enhanced after adjusting for blood cell composition. Finally, we utilize these insights to formulate best practices for SEM detection and introduce a novel R package,SEMdetectR, which utilizes parallel programming for efficient SEM detection with comprehensive options for detection, filtering, and analysis.
Tertiary-interaction characters enable fast, model-based structural phylogenetics beyond the twilight zone
Authors: Puente-Lelievre Caroline , Malik Ashar J. , Douglas Jordan , Ascher David , Baker Matthew , Allison Jane , Poole Anthony , Lundin Daniel , Fullmer Matthew , Bouckert Remco , Kim Hyunbin , Steinegger Martin , Matzke Nicholas
Published: December 2023

Protein structure is more conserved than protein sequence, and therefore may be useful for phylogenetic inference beyond the “twilight zone” where sequence similarity is highly decayed. Until recently, structural phylogenetics was constrained by the lack of solved structures for most proteins, and the reliance on phylogenetic distance methods which made it difficult to treat inference and uncertainty statistically. AlphaFold has mostly overcome the first problem by making structural predictions readily available. We address the second problem by redeploying a structural alphabet recently developed for Foldseek, a highly-efficient deep homology search program. For each residue in a structure, Foldseek identifies a tertiary interaction closest-neighbor residue in the structure, and classifies it into one of twenty “3Di” states. We test the hypothesis that 3Dis can be used as standard phylogenetic characters using a dataset of 53 structures from the ferritin-like superfamily. We performed 60 IQtree Maximum Likelihood runs to compare structure-free, PDB, and AlphaFold analyses, and default versus custom model sets that include a 3DI-specific rate matrix. Analyses that combine amino acids, 3Di characters, partitioning, and custom models produce the closest match to the structural distances tree of Malik et al. (2020), avoiding the long-branch attraction errors of structure-free analyses. Analyses include standard ultrafast bootstrapping confidence measures, and take minutes instead of weeks to run on desktop computers. These results suggest that structural phylogenetics could soon be routine practice in protein phylogenetics, allowing the re-exploration of many fundamental phylogenetic problems.
Inhibition of hypoxia-inducible factors suppresses subretinal fibrosis
Authors: Shoda Chiho , Lee Deokho , Miwa Yukihiro , Yamagami Satoru , Nakashizuka Hiroyuki , Nimura Kazumi , Okamoto Kazutoshi , Kawagishi Hirokazu , Negishi Kazuno , Kurihara Toshihide
Published: December 2023

Age-related macular degeneration (AMD) is a common cause of vision loss. The aggressive form of AMD is associated with ocular neovascularization and subretinal fibrosis, representing a responsive outcome against neovascularization mediated by epithelial-mesenchymal transition of retinal pigment epithelium cells. A failure of the current treatment (anti-vascular endothelial growth factor therapy) has also been attributed to the progression of subretinal fibrosis. Hypoxia-inducible factors (HIFs) increase gene expressions to promote fibrosis and neovascularization. HIFs act as a central pathway in the pathogenesis of AMD. HIF inhibitors may suppress ocular neovascularization. Nonetheless, further investigation is required to unravel the aspects of subretinal fibrosis. In this study, we used RPE-specific HIFs or von Hippel-Lindau (VHL, a regulator of HIFs) conditional knockout (cKO) mice, along with pharmacological HIF inhibitors, to demonstrate the suppression of subretinal fibrosis. Fibrosis was suppressed by treatments of HIF inhibitors, and similar suppressive effects were detected in RPE-specificHif1a/Hif2a-andHif1a-cKO mice. Promotive effects were observed in RPE-specificVhl-cKO mice, where fibrosis-mediated pathologic processes were evident. Marine products’ extracts and their component taurine suppressed fibrosis as HIF inhibitors. Our study shows critical roles of HIFs in the progression of fibrosis, linking them to the potential development of therapeutics for AMD.
Functional divergence shaped the network architecture of plant immune receptors
Authors: Huang Ching-Yi , Huang Yu-Seng , Sugihara Yu , Wang Hung-Yu , Huang Lo-Ting , Lopez-Agudelo Juan Carlos , Chen Yi-Feng , Lin Kuan-Yu , Chiang Bing-Jen , Toghani AmirAli , Kourelis Jiorgos , Derevnina Lida , Wu Chih-Hang
Published: December 2023

In solanaceous plants, several sensor NLRs and their helper NLRs, known as NRC, form a complex network to confer immunity against pathogens. While the sensor NLRs and downstream NRC helpers display diverse genetic compatibility, the evolution and molecular basis of the complex network structure remained elusive. Here we demonstrated that functional divergence of NRC3 variants has shaped the genetic architecture of the NLR network. Natural NRC3 variants form three allelic groups displaying distinct compatibilities with sensor NLRs. Ancestral sequence reconstruction and analyses of natural and chimeric variants identified six key amino acids involved in sensor-helper compatibility, with two residues critical for subfunctionalization. Co-functioning Rpi-blb2 and NRC3 variants showed stronger transient interactions upon effector detection, with NRC3 membrane-associated complexes forming subsequently. Our findings reveal how mutations in helper NLRs, particularly NRC3, have driven the evolution of their transient interactions with sensor NLRs, leading to subfunctionalization and contributing significantly to the complexity of the NRC network in plant immunity.

Teaser

Helper NLR subfunctionalization alters transient interactions with sensor NLRs, enhancing plant immune system complexity.
Optimizing representations for integrative structural modeling using Bayesian model selection
Authors: Arvindekar Shreyas , Pathak Aditi S. , Majila Kartik , Viswanath Shruthi
Published: December 2023

Motivation

Integrative structural modeling combines data from experiments, physical principles, statistics of previous structures, and prior models to obtain structures of macromolecular assemblies that are challenging to characterize experimentally. The choice of model representation is a key decision in integrative modeling, as it dictates the accuracy of scoring, efficiency of sampling, and resolution of analysis. But currently, the choice is usually madead hoc, manually.

Results

Here, we report NestOR (Nested Sampling forOptimizingRepresentation), a fully automated, statistically rigorous method based on Bayesian model selection to identify the optimal coarse-grained representation for a given integrative modeling setup. Given an integrative modeling setup, it determines the optimal representations from given candidate representations based on their model evidence and sampling efficiency. The performance of NestOR was evaluated on a benchmark of four macromolecular assemblies.

Availability

NestOR is implemented in the Integrative Modeling Platform (https://integrativemodeling.org) and is available athttps://github.com/isblab/nestor.

Data for the benchmark is athttps://www.doi.org/10.5281/zenodo.10360718.

Supplementary Information is available online.
Benchmarking the translational potential of spatial gene expression prediction from histology
Authors: Chan Adam S. , Wang Chuhan , Fu Xiaohang , Ghazanfar Shila , Kim Jinman , Patrick Ellis , Yang Jean YH
Published: December 2023

Spatial transcriptomics has enabled the quantification of gene expression at spatial coordinates, offering crucial insights into molecular underpinnings of diseases. In light of this, several methods predicting spatial gene expression from paired histology images have offered the opportunity of enhancing the utility of readily obtainable and cost-effective haematoxylin-and-eosin-stained histology images. To this end, we conducted a comprehensive benchmarking study encompassing six developed methods. These methods were reproduced and evaluated using HER2-positive breast tumour and human cutaneous squamous cell carcinoma datasets, followed by external validation using The Cancer Genome Atlas data. Our evaluation incorporates diverse metrics which capture the performance of predicted gene expression, model generalisability, translational potential, usability and computational efficiency of each method. Our findings demonstrate the capacity of methods to spatial gene expression from histology and highlight key areas that can be addressed to support the advancement of this emerging field.
An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity
Authors: Sahoo Ajaya Kumar , Chivukula Nikhil , Ramesh Kundhanathan , Singha Jasmine , Marigoudar Shambanagouda Rudragouda , Sharma Krishna Venkatarama , Samal Areejit
Published: December 2023

Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs), using a data-centric approach. By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.
Amino acid characteristics in protein native state structures
Authors: Škrbić Tatjana , Giacometti Achille , Hoang Trinh X. , Maritan Amos , Banavar Jayanth R.
Published: December 2023

We present a geometrical analysis of the protrusion statistics of side chains in more than 4,000 high-resolution protein structures. We employ a coarse-grained representation of the protein backbone viewed as a linear chain of Cαatoms and consider just the heavy atoms of the side chains. We study the large variety of behaviors of the amino acids based on both rudimentary structural chemistry as well as geometry. Our geometrical analysis uses a backbone Frenet coordinate system for the common study of all amino acids. Our analysis underscores the richness of the repertoire of amino acids that is available to nature to design protein sequences that fit within the putative native state folds.
Role of Ribeye PXDLS/T-binding cleft in normal synaptic ribbon function
Authors: Zhu Jie , Lv Caixia , Henry Diane , Viviano Stephen , Santos-Sacchi Joseph , Matthews Gary , Zenisek David
Published: December 2023

Non-spiking sensory hair cells of the auditory and vestibular systems encode a dynamic range of graded signals with high fidelity by vesicle exocytosis at ribbon synapses. Ribeye, the most abundant protein in the synaptic ribbon, is composed of a unique A domain specific for ribbons and a B-domain nearly identical to the transcriptional corepressor CtBP2. CTBP2 and the B-domain of Ribeye contain a surface cleft that binds to proteins harboring a PXDLS/T peptide motif. Little is known about the importance of this binding site in synaptic function. Piccolo has a well-conserved PVDLT motif and we find that overexpressed Ribeye exhibits striking co-localization with Piccolo in INS-cells, while two separate mutants containing mutations in PXDLS/T-binding region, fail to co-localize with Piccolo. Similarly, co-transfected Ribeye and a piccolo fragment containing the PVDLT region co-localize in HEK cells. Expression of wild-type Ribeye-YFP in zebrafish neuromast hair cells returns electron densities to ribbon structures and mostly rescued normal synaptic transmission and morphological phenotypes in a mutant zebrafish lacking most Ribeye. By contrast, Ribeye-YFP harboring a mutation in the PXDLS/T-binding cleft resulted in ectopic electron dense aggregates that did not collect vesicles and the persistence of ribbons lacking electron densities. Furthermore, overexpression failed to return capacitance responses to normal levels. These results point toward a role for the PXDLS/T-binding cleft in the recruitment of Ribeye to ribbons and in normal synaptic function.

Significance statement

Hair cell synaptic ribbons are evolutionarily conserved structures that appear dense in electron micrographs, extend from the release site into the cytoplasm and tether synaptic vesicles for release. Here, we show that Ribeye, the major component of the synaptic ribbon electron density is directed to ribbons via its PXDLS/T-binding site and that mutant isoforms of Ribeye with point mutations disrupting these interactions fail to rescue normal function in mutant zebrafish lacking most Ribeye.
A generative model of the hippocampal formation trained with theta driven local learning rules
Authors: George Tom M , Barry Caswell , Stachenfeld Kimberly , Clopath Claudia , Fukai Tomoki
Published: December 2023

Advances in generative models have recently revolutionised machine learning. Meanwhile, in neuroscience, generative models have long been thought fundamental to animal intelligence. Understanding the biological mechanisms that support these processes promises to shed light on the relationship between biological and artificial intelligence. In animals, the hippocampal formation is thought to learn and use a generative model to support its role in spatial and non-spatial memory. Here we introduce a biologically plausible model of the hippocampal formation tantamount to a Helmholtz machine that we apply to a temporal stream of inputs. A novel component of our model is that fast theta-band oscillations (5-10 Hz) gate the direction of information flow throughout the network, training it akin to a high-frequency wake-sleep algorithm. Our model accurately infers the latent state of high-dimensional sensory environments and generates realistic sensory predictions. Furthermore, it can learn to path integrate by developing a ring attractor connectivity structure matching previous theoretical proposals and flexibly transfer this structure between environments. Whereas many models trade-off biological plausibility with generality, our model captures a variety of hippocampal cognitive functions under one biologically plausible local learning rule.
Senolytic Intervention Improves Cognition, Metabolism, and Adiposity in Female APPNL-F/NL-FMice
Authors: Fang Yimin , Peck Mackenzie R. , Quinn Kathleen , Chapman Jenelle E. , Medina David , McFadden Samuel A. , Bartke Andrzej , Hascup Kevin N. , Hascup Erin R.
Published: December 2023

Senescent cells accumulate throughout the body and brain contributing to unhealthy aging and Alzheimer’s disease (AD). The APPNL-F/NL-Famyloidogenic AD mouse model exhibits increased markers of senescent cells and the senescence-associated secretory phenotype (SASP) in visceral white adipose tissue before plaque accumulation and cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory in APPNL-F/NL-Fmice. Thus, four month old male and female APPNL-F/NL-Fmice were treated monthly with vehicle, 5 mg/kg Dasatinib + 50 mg/kg Quercetin, or 100 mg/kg Fisetin. Blood glucose levels, energy metabolism, spatial memory, amyloid burden, and senescent cell markers were assayed. Dasatinib + Quercetin treatment in female APPNL-F/NL-Fmice increased oxygen consumption and energy expenditure resulting in decreased body mass. White adipose tissue mass was decreased along with senescence markers, SASP, blood glucose, and plasma insulin and triglycerides. Hippocampal senescence markers and SASP were reduced along with soluble and insoluble amyloid-β (Aβ)42and senescence associated-β-gal activity leading to improved spatial memory. Fisetin had negligible effects on these measures in female APPNL-F/NL-Fmice while neither senolytic intervention altered these parameters in the male mice. Considering women have a greater risk of dementia, identifying senotherapeutics appropriate for sex and disease stage is necessary for personalized medicine.
Corporate social responsibility performance and social reputation via corporate social responsibility awarding: is there a threshold effect?
Authors: Kuzey Cemil , Uyar Ali , Ellili Nejla Ould Daoud , Karaman Abdullah S.
Published: December 2023

Purpose

This study aims to examine the potential threshold effect in the association between corporate social responsibility (CSR) performance and social reputation.

Design/methodology/approach

This study includes an international and cross-sector sample covering 41 countries, nine sectors and 45,395 firm-year observations. It applies a parabolic relationship, rather than linear regressions, between CSR engagement and social reputation via CSR awarding. This implies that CSR performance should increase until a certain point to gain a social reputation but then should decrease after reaching that threshold point considering limited financial resources.

Findings

The findings of country-industry-year fixed-effects logistic regressions confirm the threshold effect with an inverted U-shaped relationship between CSR and CSR awarding. More specifically, firms increase their environmental and social engagement until a certain point, and then they reduce it after reaching a social reputation. This finding is confirmed by three dimensions of the environmental pillar (i.e. resource use, emissions and eco-innovation) as well as four dimensions of the social pillar (i.e. workforce, human rights, community and product responsibility). The findings are robust to alternative samples, alternative methodology and endogeneity concerns.

Practical implications

The findings of this study have implications for firms about the better allocation of available funds between CSR and operations. The findings could be particularly useful for CSR teams/committees of the firms who formulate CSR policies and how to mobilize firm resources for better social enhancement via environmental and social reputation.

Originality/value

This study examines deeper the nature of the association between CSR engagement and social reputation and considers the possibility of an inverted U-shaped relationship between them. The determination of a threshold effect suggests that CSR engagement increases social reputation, but once it reaches a certain point, social reputation will decrease owing to financial resource constraints.
Parameters calculation method of energetic model for symmetrical static hysteresis loop and asymmetrical minor loop
Authors: Ji Junan , Zhao Zhigang , Zhang Shi , Chen Tianyuan
Published: December 2023

Purpose

This paper aims to propose an energetic model parameter calculation method for predicting the materials’ symmetrical static hysteresis loop and asymmetrical minor loop to improve the accuracy of electromagnetic analysis of equipment.

Design/methodology/approach

For predicting the symmetrical static hysteresis loop, this paper deduces the functional relationship between magnetic flux density and energetic model parameters based on the materials’ magnetization mechanism. It realizes the efficient and accurate symmetrical static hysteresis loop prediction under different magnetizations. For predicting the asymmetrical minor loop, a new algorithm is proposed that updates the energetic model parameters of the asymmetrical minor loop to consider the return-point memory effect.

Findings

The comparison of simulation and experimental results verifies that the proposed parameters calculation method has high accuracy and strong universality.

Originality/value

The proposed parameter calculation method improves the existing parameter calculation method’s problem of relying on too much experimental data and inaccuracy. Consequently, the presented work facilitates the application of the finite element electromagnetic field analysis method coupling the hysteresis model.
Mapping the landscape of tourism cities research: a bibliometric analysis of the International Journal of Tourism Cities
Authors: Gurung Deep Jyoti , Gowreesunkar Vanessa
Published: December 2023

Purpose

This research addresses the pressing need for comprehensive studies in the rapidly evolving field of city tourism. This study aims to understand the overall performance of the International Journal of Tourism Cities (IJTC), the structure of knowledge in city tourism research and the prevalent themes and trends arising from IJTC.

Design/methodology/approach

A bibliometric analysis was conducted to scrutinize the publication patterns in IJTC. This involved examining parameters such as the annual count of published articles, the keywords used in them and their respective authors.

Findings

The findings reveal that IJTC has a growing and diverse publication output, establishing itself as a reputable and influential publication within urban tourism research. The results reflect various aspects and themes in city tourism research.

Research limitations/implications

The study has certain limitations. The data used for analysis was obtained exclusively from the Scopus database. The analysis was conducted using only one software package, Bibliometrix. Other software packages may offer different features for bibliometric analysis. The study relied exclusively on quantitative methods for data analysis. Qualitative methods could have provided more nuanced interpretations of the data.

Practical implications

Comparative analyses could be conducted between IJTC and other journals within urban tourism or related disciplines. Such research would yield valuable insights into the current state of the field and aid in identifying areas warranting further investigation.

Social implications

The findings from this study can inform the decisions and actions of various stakeholders involved in urban tourism. Practitioners and policymakers can draw from this research to make informed decisions. Existing and emerging authors can identify relevant topics for their research. Readers can access pertinent information for their needs.

Originality/value

This study offers a unique contribution by thoroughly comprehending the performance of IJTC between 2015 and 2023. It progresses the existing body of knowledge on city tourism research by examining its current status and future trends.
Study on the influence of non-Gaussian honing surface on contact and flow characteristics
Authors: Tang Yihu , Huang Li , Meng Xianghui
Published: December 2023

Purpose

The contact and lubrication performances, which were previously estimated assuming a Gaussian surface, are insufficient due to the non-Gaussian surface characteristics of the honing liner. The purpose of this study is to analyze the liner honing surface and examine its effects on the contact and flow performance.

Design/methodology/approach

The fast Fourier transform (FFT) method was used to generate the liner honing texture. Subsequently, an elastoplastic contact model based on boundary element theory was constructed and simulated for the honing surface. The results were compared with those obtained using a Gaussian surface. In addition, flow factors of the honing surfaces were also compared.

Findings

The contact pressure and flow factors demonstrate significant disparities when dealing with non-Gaussian surfaces. In the deterministic model, the pressure exhibits considerably diminished magnitudes and a more evenly distribution. Moreover, when the gap between surfaces is narrow, the discrepancy in flow factor across different directions on the real honing surface becomes more prominent compared with the Gaussian surface.

Originality/value

The model incorporates the influence of the non-Gaussian honing surface, thereby enabling more accurate prediction.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-07-2023-0198/
Financial management and family business: a perspective article
Authors: Strong John Scott
Published: December 2023

Purpose

This study aims to review major themes and findings of research into financial management of family business and to suggest new directions for future research.

Design/methodology/approach

This is a perspective article beginning with literature review to summarize prior research and to identify main findings and issues. The paper then develops themes, questions and opportunities for future research.

Findings

This paper presents a summary of principal research streams in the financial management of family business. Prior research has found significant differences in financial performance, in financial policies and in ownership and governance structures and behavior. These research findings vary by industry, by country and by stage of economic development. While extensions of these streams will add additional richness to the author’s understanding of finance in family business, recent innovations in the role and organization of the firm and in access to key resources suggest promising new research paths. There are also important lessons from financial practices in family business that have broader applicability.

Originality/value

This is a perspective article suggesting that many financial and governance issues central to family business have broader applicability to nonfamily business. Substantial value can be added by applying these learnings to a broader corporate finance context. Innovations in financing, governance and organizational design are transforming financial management in family business. In addition, changes in markets and industries create new opportunities for financing family business and for new strategic opportunities.
Dialogue for strategy implementation: how framing processes enable the evolution of new opportunities
Authors: Bellis Paola , Magnanini Silvia , Verganti Roberto
Published: December 2023

Purpose

Taking the dialogic organizational development perspective, this study aims to investigate the framing processes when engaging in dialogue for strategy implementation and how these enable the evolution of implementation opportunities.

Design/methodology/approach

Through a qualitative exploratory study conducted in a large multinational, the authors analyse the dialogue and interactions among 25 dyads when identifying opportunities to contribute to strategy implementation. The data analysis relies on a process-coding approach and linkography, a valuable protocol analysis for identifying recursive interaction schemas in conversations.

Findings

The authors identify four main framing processes – shaping, unveiling, scattering and shifting – and provide a framework of how these processes affect individuals’ mental models through increasing the tangibility of opportunities or elevating them to new value hierarchies.

Research limitations/implications

From a theoretical perspective, this study contributes to the strategy implementation and organizational development literature, providing a micro-perspective of how dialogue allows early knowledge structures to emerge and shape the development of opportunities for strategy implementation.

Practical implications

From a managerial perspective, the authors offer insights to trigger action and change in individuals to contribute to strategy when moving from formulation to implementation.

Originality/value

Rather than focusing on the structural control view of strategy implementation and the role of the top management team, this study considers strategy implementation as a practice and what it takes for organizational actors who do not take part in strategy formulation to enact and shape opportunities for strategy implementation through constructive dialogue.
How does a shared cognitive schema emerge and evolve in an interdisciplinary research team: a case study of IAM
Authors: Duan Xuening , Chang Yu , Huang Wei , Hasan Md Moynul
Published: December 2023

Purpose

A shared cognitive schema is the fundamental source of tacit understanding within a team. This study aims to address how such a shared cognitive schema emerges and evolves in an interdisciplinary research team.

Design/methodology/approach

This study uses an exploratory single case study to analyze the emergence and evolution of a shared cognitive schema in an interdisciplinary research team systematically. The authors spent more than two years collecting data from the IAM team via semistructured interviews, archival data and observation. Subsequently, a framework for the resulting mechanism model was developed by analyzing the data using a three-step process.

Findings

This study shows that as the interdisciplinary research team develops, the shared cognitive schema passes through three stages: overlapping cognitive schema, complementary cognitive schema and synergetic cognitive schema. The mechanisms of overlap, complement and synergy play important roles. The convergent roles of partner-based recruiting, knowledge categorization and following the existing institution facilitate the overlapping of knowledge structures. Complementary cognitive schema sharing is facilitated by interdisciplinary member selection, knowledge stock expansion and the effects of accomplished mentors. The synergetic behaviors of group voice, interactive cognition and adaptive learning facilitate synergetic cognitive schema sharing.

Originality/value

This study is the first to discuss the emergence and evolution of a shared cognitive schema at the microlevel of knowledge structure and belief structure. It offers a new theoretical perspective on the development rules of scientific research teams and provides practical enlightenment regarding the establishment and operation of interdisciplinary research teams.
Spillover effects and transmission of shocks in Visegrad equity markets
Authors: Aliu Florin , Asero Vincenzo , Asllani Alban , Kučera Jiří
Published: December 2023

Purpose

Paper aims to investigate the interdependencies and spillover effects that the Visegrad (V4 hereafter) Equity Markets hold on each other. The V4 group stands for the political alliance of four Central European countries: Poland, the Czech Republic, Hungary and Slovakia.

Design/methodology/approach

The study uses Wavelet coherence, dynamic conditional correlation GARCH (1, 1) and unrestricted vector autoregression (VAR) methodologies. Daily data series (covering the period from January 2, 2006, to February 2, 2023) are analyzed to assess coherence, time-varying conditional correlation and shock transmission among the V4 Equity Markets.

Findings

Wavelet analysis reveals that the Slovak equity market does not maintain coherence with three other equity markets. The time-varying conditional correlation documents for the high interdependence during the COVID-19 outbreak of the four indexes. The VAR estimates reveal that shocks in the Warsaw equity market are easily transmitted in Prague and Budapest exchanges but not in Bratislava. The results show that the Slovak equity market tends to be isolated from the influence of other three V4 exchanges. This isolation is attributed to its size, limited volume and adoption of the euro in 2009. The study emphasizes the Slovak financial system’s gravitation toward the Eurozone after euro adoption.

Originality/value

Notably, the findings provide important signals for local and international investors as the results cover four significant international shocks. The global meltdown of 2008/09, the Greek debt crisis of 2010/11, the COVID-19 pandemic and the Russia-Ukraine war.