bluuebunny/crossref_metadata_2025 huggingface dataset:
The Infraslow Fluctuation of Sigma Power During Sleep: Links to Markers of Arousal and Memory Reactivation Across Development
Authors: Dimitriades Maria E. , Osorio-Forero Alejandro , Fattinger Sara , von Arx Simone , Kurth Salome , Pugin Fiona , Jaramillo Valeria , Volk Carina , Krugliakova Elena , Furrer Melanie , Leach Sven , Achermann Peter , Gerstenberg Miriam , Huber Reto
Published: November 2024

Sleep is both a state of disconnection from the environment and a critical period for restoration. But how does sleep balance responsiveness with the protection of key functions? The infraslow fluctuation of sigma power (ISFS)—the clustering of sleep spindles over 10-100 seconds—is thought to regulate this trade-off in rodents. However, the organization of arousal and memory reactivation markers within the human ISFS and its conservation in younger ages remain unclear. This study characterizes the ISFS from childhood to young adulthood (N = 154; ages 8-26), examining its relationship with functional markers. Results indicate that the ISFS is present across all ages, with frequency, variability, and strength increasing from early to late adolescence. Notably, markers of arousal and memory reactivation are organized within the spindle-rich ISFS peak. The consistent presence and organization of the ISFS suggest it is intrinsic to sleep, with adolescence marking a dynamic window. These insights may guide interventions to promote healthier sleep across development.
Cocaine, via ΔFosB, remodels gene expression and excitability in ventral hippocampus
Authors: Eagle Andrew L. , Doyle Marie A. , Sugimoto Chiho , Dykstra Megan , Kuhn Hayley M. , Murray Brooklynn R. , Bastle Ryan M. , Jin He , Maze Ian , Mazei-Robison Michelle S. , Robison Alfred J.
Published: November 2024

Ventral hippocampus (vHPC) CA1 pyramidal neurons send glutamatergic projections to nucleus accumbens (NAc), and this vHPC-NAc circuit mediates cocaine seeking and reward, but it is unclear whether vHPC-NAc neuron properties are modulated by cocaine exposure to drive subsequent behavior. The immediate early gene transcription factor ΔFosB is induced throughout the brain by cocaine and is critical for cocaine seeking, but it’s function in vHPC-NAc neurons is not understood. We now show that circuit-specific knockout of ΔFosB in vHPC-NAc neurons impaired cocaine reward expression and forced abstinence-induced seeking. We also found that vHPC-NAc excitability was decreased by experimenter-administered repeated cocaine and cocaine self-administration, and this cocaine-induced excitability decrease was mediated by ΔFosB expression. To uncover the mechanism of this change in circuit function, we used circuit-specific translating ribosome affinity purification (TRAP) to assess cocaine-induced, ΔFosB-dependent changes in gene expression in vHPC-NAc. We found that cocaine causes a ΔFosB-dependent increase in the expression of calreticulin, an ER-resident calcium-buffering protein. Calreticulin expression mediated vHPC-NAc excitability and was necessary for cocaine reward. These findings uncover a novel, non-canonical mechanism by which cocaine increases calreticulin in vHPC leading to decreased vHPC-NAc excitability and drives cocaine seeking and reward.
Lignocellulose Degradation in Bacteria and Fungi for Biomass Conversion
Authors: Hsin Kuan-Ting , Lee HueyTyng , Lin Ying-Chung Jimmy , Chen Pao-Yang
Published: November 2024

Lignocellulose biomass is one of the most abundant resources for sustainable biofuels. However, scaling up the biomass-to-biofuels conversion process for widespread usage is still pending. Bottlenecks during the process of enzymatic hydrolysis are the high cost of enzymes and the labor-intensive need for substrate-dependent enzyme mixtures. Current research efforts are therefore targeted at searching for or engineering lignocellulolytic enzymes of high efficiency. One way is to engineer multi-enzyme complexes that mimic the bacterial cellulosomal system, known to increase degradation efficiency up to 50-fold when compared to freely-secreted enzymes. However, these designer cellulosomes are instable and less efficient than wild type cellulosomes. Fungi cellulosomes discovered in recent years have significant differences from bacterial counterparts and hold great potential for industrial applications, both as designer cellulosomes and as additions to the enzymatic repertoire. Up to date, they are only found in a few anaerobic fungi. In this review, we extensively compared the degradation mechanisms in bacteria and fungi, and highlighted the essential gaps in applying these mechanisms in industrial applications. To better understand cellulosomes in microorganisms, we examined their sequences in 66,252 bacterial species and 823 fungal species and identified several bacterial species that are potentially cellulosome-producing. These findings act as a valuable resource in the biomass community for further proteomic and genetic sequence analysis. We also collated the current strategies of bioengineering lignocellulose degradation to suggest concepts that could be favorable for industrial usage.
Inhibiting DPP4 activity protects hiPSC-derived steatotic HLCs by supporting fatty acid and purine metabolism and dampening inflammation
Authors: Loerch Christiane , Wruck Wasco , Julian Reiss , Adjaye James , Graffmann Nina
Published: November 2024

Background and Aim

Metabolic dysfunction-associated steatotic liver disease (MASLD/MAFLD) has a high prevalence and high co-morbidity for other diseases. Due to the complexity of this multifactorial disease, therapy options are still rather limited. We employed anin vitropluripotent stem cell-based model to decipher basic disease-associated molecular pathways and to study the mode of action of potential drugs.

Methods

We induced the steatosis phenotype in human induced pluripotent stem cell (iPSC) derived hepatocyte-like cells (HLCs) by oleic acid (OA)-feeding and confirmed regulation of clinically relevant pathways by NGS-based global transcriptomic analyses. Analysis of the secretome of steatotic HLCs revealed Dipeptidyl peptidase 4 (DPP4) as a potential key mediator of the disease. To further elucidate its role in the development of MAFLD, we inhibited DPP4 activity with Vildagliptin (VILDA) and analyzed the global transcriptome changes as well as specific gene and protein expression of steatosis-associated genes with and without DPP4 inhibition.

Results

MAFLD-associated pathways such as PPAR– and TNF signaling were differentially regulated in hiPSC-derived steatotic HLCs. We found increased hepatic DPP4 activity and secretion upon OA. Fatty acid and purine metabolism and inflammation response pathways were improved upon DPP4 inhibition.

Conclusion

Our HLC-model confirmed clinically-relevant association of DPP4 with metabolism and inflammation which foster the development of MAFLD. Inhibiting DPP4 with VILDA partially relieved the steatotic phenotype.

Impact and implications

Given the difficulties of identifying suitable anti-MAFLD drugs, novel model systems are urgently needed. Ourin vitroHLC-model reproduced DPP4-dependent aspects of the disease and responded positively to Vildagliptin treatment. Further elucidation of the role of DPP4 in the etiology of MAFLD is warranted.
Correction of RBFOX1 deficit rescues Huntington’s disease mis-splicing and pathology
Authors: Lozano-Muñoz David , Elorza Ainara , Mayor Lucía , Santos-Galindo María , Lucas-Santamaría Miriam , Parras Alberto , Lucas José J.
Published: November 2024

RNA mis-splicing correction therapies have been developed for neurological disorders like spinal muscular atrophy and neuronal ceroid lipofuscinosis. In Huntington’s disease (HD), pathogenic mis-splicing was initially observed in genes linked to neurodegeneration, such asHTTitself,MAPT, andTAF1. Later, genome-wide analyses identified a broader mis-splicing signature in HD brains, involving additional neurodegeneration-related genes. Correcting each mis-spliced gene individually would be unfeasible, highlighting the need to target upstream splicing factors altered in HD. Our previous motif-enrichment analyses of intronic sequences flanking the exons mis-spliced in HD identified RBFOX and U2AF2 as candidate splicing factors, both of which are reduced in HD brains. In this study, we tested their pathogenic relevance generating conditional transgenic mouse models that overexpress RBFOX1 or U2AF2 in forebrain neurons and combining them with HD mice. Our results show that moderate overexpression of RBFOX1, but not U2AF2, corrects multiple HD-associated mis-splicing events and alleviates HD mice neuropathology and motor symptoms. These findings demonstrate that RBFOX1 downregulation contributes to HD pathology and underscore the therapeutic potential of strategies aimed at increasing RBFOX1 levels.
Spinal cord phosphoproteome of a SCA2/ALS13 mouse model reveals alteration of ATXN2-N-term SH3-actin interactome and of autophagy via WNK1-MYO6-OPTN-SQSTM1
Authors: Almaguer-Mederos Luis-Enrique , Kandi Arvind Reddy , Sen Nesli-Ece , Canet-Pons Júlia , Berger Luca-Malena , Key Jana , Brunstein Melinda-Elaine , Münch Christian , Gispert Suzana , Auburger Georg
Published: November 2024

Toxic polyglutamine (polyQ) expansions in ATXN2 trigger neurodegenerative processes, causing Spinocerebellar Ataxia type 2 (SCA2), and enhancing TDP-43-dependent pathology in Amyotrophic Lateral Sclerosis (ALS) / Fronto-Temporal Dementia (FTD). Primary disease events can be compensated transiently, delaying disease manifestation. To define potential therapy targets, we documented how cells modify their phospho-signals and how the ATXN2 interactome changes, using preferentially affected nervous tissues from end-stageAtxn2-CAG100-KnockIn mice. The spinal cord phosphorylome revealed massive hyperphosphorylations flanking the polyQ expansion in ATXN2 and for SQSTM1, and moderate hyperphosphorylations also for ALS proteins OPTN, UBQLN2, TNIP1 and TBK1-targeted TAX1BP1, versus strong hypophosphorylations of WNK1, SPARCL1 and PSMD9. Significant enrichments of SH3-containing proteins, autophagy / endocytosis factors, and actin modulators could be explained by N-terminal, polyQ-adjacent, proline-rich motifs in ATXN2. Coimmunoprecipitation profiling in cerebellum documented known associations with RNA-binding proteins like PABPC1 and TDP-43 with its modifier PPIA to decrease upon expansion, contrasting with increased binding of SH3-proteins, like MYO6, RPL21 and DLG4. Validation of protein and mRNA levels in mouse spinal cord, and embryonic fibroblasts or patient fibroblasts after bafilomycin or arsenite treatment, observed polyQ-dependent OPTN deficiency and SQSTM1 induction impairment. Overall, this combined phosphoproteome / interactome study efficiently revealed key pathways and molecular events.
Sociality shapes the adaptive response of breeders to harsh thermal environments? An experiment in a burying beetle
Authors: Ma Donghui , Ma Long , Versteegh Maaike A. , Komdeur Jan
Published: November 2024

The rapid pace of environmental change seems to outstrip the evolutionary response rates of many species. Physiological, morphological, and behavioral plasticity alone may also not suffice to cope with environments’ drastic changes, potentially hindering individuals’ ability to adapt. Therefore, it has been proposed that social flexibility may be a powerful mechanism for fast adaptation, but empirical evidence is lacking.

We investigated the combined effects of manipulated social conditions and ambient temperature during the reproductive phase on parental care, reproductive success, and offspring performance of the burying beetle (Nicrophorus vespilloides), a facultative social breeding insect.

We conducted a mixed factorial design experiment, establishing four categories of social conditions during breeding (no-care, unifemale-care, biparenta-care, and multiple-care) alongside two thermal conditions (benign: 20°C and harsh: 23°C). Additionally, dispersed larvae produced from each of these breeding conditions were allocated to climate rooms maintained at either 20°C or 23°C for pupation. Data on brood size, brood mass, dispersed larval weight, larval development duration, body size and lifespan of newly eclosed beetles, and parental care were collected

Our results showed that (1) harsh temperature and the without-care condition (i.e., no-care compared to the other three social conditions) reduced brood size, brood mass, body size of newly eclosed beetles; (2) social and ambient thermal conditions had interactive effects on dispersed larval weight, larval development duration, and newly eclosed beetles’ lifespan; and (3) harsh temperature reduced both individual and total parental care, whereas sociality had opposing effects: individual care decreased, but total care increased from unifemale-care to biparental-care and multiple-care conditions.

Our findings shed light on the critical role of sociality in modulating the adaptive response of individuals to harsh thermal environments, one of the ecological problems exacerbated by ongoing global warming.
Complementation of a human disease phenotype in vitro by intercellular mRNA transfer
Authors: Haimovich Gal , Dasgupta Sandipan , Ravi Anand Govindan , Gerst Jeffrey E.
Published: November 2024

There is growing evidence that full-length mRNAs undergo intercellular transfer through long, thin cytoplasmic connections called tunneling nanotubes (TNTs), but whether transferred mRNAs are translated and effect cellular changes post-transfer is unknown. Using multiple lines of evidence, we show that transferred mRNAs undergo translation and can fully complement the phenotype of genetic mutationsin vitro. For example, the human peroxisome biogenesis disorder, Zellweger Syndrome, results from mutations in genes like PEX5 and PEX6. We demonstrate that the co-culture of patient-derived PEX6 mutant fibroblasts or PEX5 knock-out cells with wild-type cells leads tode novoperoxisome biogenesis. Complementation occurs by TNT-mediated mRNA transfer and translation in acceptor cells and not by peroxisome transfer. We provide additional examples of genetic complementation via transfer of mRNAs encoding the HSF1 transcription factor or CRE recombinase. Our study provides evidence for the physiological significance of mRNA transfer and suggests a new approach for mRNA therapeutics.

Abstract Figure
Single Objective Light Sheet Microscopy allows high-resolutionin vivobrain imaging of Drosophila
Authors: Tassara Francisco J. , Barella Mariano , Simó Lourdes , Folgueira Serrao M. Mailén , Rodríguez-Caron Micaela , Ispizua Juan Ignacio , Ellisman Mark H. , de la Iglesia Horacio O. , Ceriani M. Fernanda , Gargiulo Julián
Published: November 2024

In vivoimaging of dynamic sub-cellular brain structures inDrosophila melanogasteris key to understanding several phenomena in neuroscience. However, its implementation has been hindered by a trade-off between spatial resolution, speed, photobleaching, phototoxicity, and setup complexity required to access the specific target regions of the small brain ofDrosophila. Here, we present a single objective light-sheet microscope, customized forin vivoimaging of adult flies and optimized for maximum resolution. With it, we imaged the axonal projections of small lateral ventral neurons (known as s-LNvs) in intact adult flies. We imaged the plasma membrane, mitochondria, and dense-core vesicles with high spatial resolution up to 370 nm, ten times lower photobleaching than confocal microscopy, lower invasiveness and complexity in sample mounting than alternative light-sheet technologies, and without relying on phototoxic pulsed infrared lasers. This unique set of features paves the way for new long-term, dynamic studies in the brains of living flies.
Real-Time Spatiotemporal Filtering for Artifact-Free EEG during Electrical Neurostimulation
Authors: Menrath David , Woller Joshua P. , Gharabaghi Alireza
Published: November 2024

Abstract

Combining electrical neurostimulation with electroencephalography (EEG) for adaptive neurostimulation remains challenging due to the presence of stimulation artifacts in the recorded signal. Interpretation of EEG activity concurrent with stimulation requires real-time filtering of this noisy signal. While traditional frequency domain filters can suppress activity within frequency bands, they fail to differentiate sources in situations when there is a shared frequency characteristic between brain activity and stimulation signal. Here we present a new real-time denoising approach that combines spatial filtering and dynamic filter application. The spatiotemporal filter can suppress stimulation artifacts that share frequency bands with the brain signal in real-time while preserving the full spectral power. The spatial filter is also dynamically updated to account for possible changes in artifact topography. Finally, the filter is robust to changes of stimulation intensity, frequency and duration, enabling reliable denoising performance for inclusion in brain state-based closed-loop stimulation.
Loss of mitochondrial enzyme GPT2 leads to reprogramming of synaptic glutamate metabolism
Authors: Baytas Ozan , Davidson Shawn M. , Kauer Julie A. , Morrow Eric M.
Published: November 2024

Recessive loss-of-function mutations in the mitochondrial enzyme Glutamate Pyruvate Transaminase 2 (GPT2) cause intellectual disability in children. Given this cognitive disorder, and because glutamate metabolism is tightly regulated to sustain excitatory neurotransmission, here we investigate the role of GPT2 in synaptic function. GPT2 catalyzes a reversible reaction interconverting glutamate and pyruvate with alanine and alpha-ketoglutarate, a TCA cycle intermediate; thereby, GPT2 may play an important role in linking mitochondrial tricarboxylic acid (TCA) cycle with synaptic transmission. In mouse brain, we find that GPT2 is enriched in mitochondria of synaptosomes (isolated synaptic terminals). Loss of Gpt2 in mouse appears to lead to reprogramming of glutamate and glutamine metabolism, and to decreased glutamatergic synaptic transmission. Whole-cell patch-clamp recordings in pyramidal neurons of CA1 hippocampal slices fromGpt2-null mice reveal decreased excitatory post-synaptic currents (mEPSCs) without changes in mEPSC frequency, or importantly, changes in inhibitory post-synaptic currents (mIPSCs). Additional evidence of defective glutamate release included reduced levels of glutamate released fromGpt2-null synaptosomes measured biochemically. Glutamate release from synaptosomes was rescued to wild-type levels by alpha-ketoglutarate supplementation. Additionally, we observed evidence of altered metabolism in isolatedGpt2-null synaptosomes: decreased TCA cycle intermediates, and increased glutamate dehydrogenase activity. Notably, alterations in the TCA cycle and the glutamine pool were alleviated by alpha-ketoglutarate supplementation. In conclusion, our data support a model whereby GPT2 mitochondrial activity may contribute to glutamate availability in pre-synaptic terminals, thereby highlighting potential interactions between pre-synaptic mitochondrial metabolism and synaptic transmission.
Response of neuronal populations to phase-locked stimulation: model-based predictions and validation
Authors: Mirkhani Nima , McNamara Colin G. , Oliviers Gaspard , Sharott Andrew , Duchet Benoit , Bogacz Rafal
Published: November 2024

Background

Modulation of neuronal oscillations holds promise for the treatment of neurological disorders. Nonetheless, stimulating neuronal populations in a continuous open-loop manner can lead to side effects and suboptimal efficiency. Closed-loop strategies such as phase-locked stimulation aim to address these shortcomings by offering a more targeted modulation. While theories have been developed to understand the neural response to stimulation, their predictions have not been thoroughly tested using experimental data.

Objective

We aimed to test the predictions of a mathematical model regarding the response of neuronal populations to phase-locked stimulation.

Methods

Using a coupled oscillator model, we expanded on two key predictions describing the response to stimulation as a function of the phase and amplitude of ongoing neural activity. To investigate these predictions, we analyzed electrocorticogram (ECoG) recordings from a previously conducted study in Parkinsonian rats, and extracted the corresponding phase and response curves.

Results

We demonstrated that the amplitude response to stimulation is strongly correlated to the derivative of the phase response (ρ> 0.8) in all animals except one, thereby validating a key model prediction. The second prediction postulated that the stimulation becomes ineffective when the network synchrony is high, a trend that appeared missing in the data. Our analysis explained this discrepancy by showing that the neural populations in Parkinsonian rats did not reach the level of synchrony for which the theory would predict ineffective stimulation.

Conclusions

Our results highlight the potential of fine-tuning stimulation paradigms informed by mathematical models that consider both the ongoing phase and amplitude of the targeted neural oscillation.
Long noncoding RNAHSCHARMEpromotes the maturation of stem cells-derived cardiomyocytes by controlling gene regulatory networks altered in human cardiomyopathies
Authors: Buonaiuto Giulia , Desideri Fabio , Storari Giulio , Palma Alessandro , Santini Tiziana , Trisciuoglio Daniela , Ballarino Monica
Published: November 2024

A growing body of evidence suggests that tissue-specific long noncoding RNAs (lncRNA) play pivotal roles in the heart. Here, we exploited the synteny between the mouse and human genomes to identify the novel lncRNAHSCHARME(HumanSyntenic CHARME) and combined single-cell transcriptomics, CAGE-seq data, RNA-FISH imaging and CRISPR-Cas9 genome editing to document its role in cardiomyogenesis. We found that the functional inactivation ofHSCHARMEin hiPSC-derived cardiomyocytes (CM) impairs the expression of calcium handling and contraction genes, with a consequent decline of CM maturation and contractile functions. Consistent with a possible association with disease, large-scale analysis of the lncRNA expression across cardiomyopathy patients revealed increased levels ofHSCHARMEin hypertrophic (HCM) and dilated (DCM) hearts and identified a subset of diseased-associated targets whose expression can be modulated throughHSCHARMEdosage. Overall, our data unlock the potential ofHSCHARMEas a novel non-coding regulator of CM physiology and open new possibilities for the therapeutic application of the lncRNA in disease.
In VitroFertilization induces reproductive changes in male mouse offspring and has multigenerational effects
Authors: Rhon-Calderon Eric A. , Hemphill Cassidy N. , Savage Alexandra J. , Riesche Laren , Schultz Richard M. , Bartolomei Marisa S.
Published: November 2024

In vitrofertilization (IVF) is a non-coital method of conception used to treat human infertility. Although IVF is viewed as largely safe, it is associated with adverse outcomes in the fetus, placenta, and adult offspring life. Because studies focusing on the effect of IVF on the male reproductive system are limited, we used a mouse model to assess the morphological and molecular effects of IVF on male offspring. We evaluated three developmental stages: 18.5-day fetuses and 12- and 39-week-old adults. Regardless of age, we observed changes in testicular-to-body weight ratios, serum testosterone levels, testicular morphology, gene expression, and DNA methylation. Also, sperm showed changes in morphology and DNA methylation. To assess multigenerational phenotypes, we mated IVF and naturally conceived males with wild-type females. Offspring from IVF males exhibited decreased fetal weight-to-placental weight ratios and changes in placenta morphology regardless of sex. At 12-weeks-of-age, offspring showed higher body weights and differences in glucose, triglycerides, insulin, total cholesterol, HDL and LDL/VLDL levels. Both sexes showed changes in gene expression in liver, testes and ovaries, and decreased global DNA methylation. Collectively, our findings demonstrate that male IVF offspring exhibit abnormal testicular and sperm morphology and molecular alterations and transmit defects multigenerationally.
Employing biological sex as a primary variable can restrict our understanding of behavioral diversity (and sex differences) in psychostimulant activity
Authors: Yao Gabriella , Job Martin O
Published: November 2024

Background

In addition to representing distinct biological sex groups, males and females are also individuals expressing behavioral diversity. Our MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model suggests that, with respect to behavior, grouping according to the individual reveals groups with differences that exceed biological sex-related differences, but this needs further clarification. We hypothesized that, compared to the current model (grouping by biological sex), the MISSING model (grouping by individual attributes) was the more effective grouping strategy to identify behavioral diversity.

Methods

We conducted experiments in rats to determine the locomotor activity (in 90 min) following intraperitoneal injections of saline (n = 12 males, n = 11 females) and cocaine (n = 8 males, n = 11 females). For the current model, we compared males versus females using unpaired t-tests. For the MISSING model, we identified clusters of individuals (males and females) using normal mixtures clustering analysis of several behavioral variables and employed unpaired t-tests to compare clusters and Two-way ANOVA to determine if there were any SEX by cluster interactions. For both models, we employed linear regression analysis to compare relationships between variables and Two-way repeated measures ANOVA to analyze locomotor activity time course.

Results

For both the saline and cocaine groups, the MISSING model identified two behavioral clusters with differences that exceeded any differences due to biological sex.

Conclusions

The MISSING model suggests that employing biological sex as a primary variable can obscure our understanding of sex and individual differences in psychostimulant activity.
A high-quality genome of the mass-blooming desert plantCistanthe longiscapaand its photosynthetic behavior related to drought and life history
Authors: Chomentowska Anri , Raimondeau Pauline , Wei Lan , Jose Eleanor G.D. , Dauerman Sophie G. , Davis Virginia Z. , Moreira-Muñoz Andrés , Peralta Iris E. , Edwards Erika J.
Published: November 2024

Crassulacean acid metabolism (CAM) photosynthesis has independently evolved many times in arid-adapted plant lineages.Cistanthe longiscapa(Montiaceae), a desert mass-blooming annual, can upregulate CAM facultatively upon stress such as drought. Few studies, however, consider life history stages when measuring CAM activity or its facultative onset.

To test the effect of drought and flowering on photosynthetic activity, we assayedCistantheindividuals in fully-watered and drought conditions, as well as fully-watered individuals at pre-flowering and flowering life stages. We assembled and annotated a chromosome-scale genome ofC. longiscapaand compared it with the genome ofPortulaca amilisand analyzed differential gene expression.

Results show significantly upregulated CAM in drought conditions as compared to fully-watered conditions; furthermore, flowering individuals showed slightly higher CAM activity as compared to pre-flowering plants, even when fully-watered. Differential gene expression analyses provide preliminary support for the possible co-regulation of CAM expression and reproduction.

We emphasize the potentially missed significance of life history in the CAM literature, and consider how the CAM biochemical module could become co-opted into other plant behaviors and responses, such as the shift to reproduction or flowering in annuals.
Differentially expressed growth factors and cytokines drive phenotypic changes in transmissible cancers
Authors: Maskell Kathryn G. , Schönbichler Anna , Flies Andrew S. , Patchett Amanda L.
Published: November 2024

The Tasmanian devil is threatened by two deadly transmissible Schwann cell cancers. A vaccine to protect Tasmanian devils from both devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2), and improved understanding of the cancer cell biology, could support improved conservation actions. Previous transcriptomic analysis has implicated phenotypic cellular plasticity as a potential immune escape and survival mechanism of DFT1 cells. This phenotypic plasticity facilitates transition from a myelinating Schwann cell to a repair Schwann cell phenotype that exhibits mesenchymal characteristics. Here, we have identified cytokines and growth factors differentially expressed across DFT cell phenotypes and investigated their role in driving phenotypic plasticity and oncogenic properties of DFT cells. Our results show that NRG1, IL16, TGFβ1, TGFβ2 and PDGFAA/AB proteins have significant and distinct effects on the proliferation rate, migratory capacity and/or morphology of DFT cells. Specifically, PDGFR signalling, induced by PDGFAA/AB, was a strong enhancer of cell proliferation and migration, while TGFβ1 and TGFβ2 induced epithelial-mesenchymal transition (EMT)-like changes, inhibited proliferation and increased migratory capacity. These findings suggest complex interactions between cytokine signalling, phenotypic plasticity, growth and survival of DFTs. Signalling pathways implicated in the propagation of DFT are potential targets for therapeutic intervention and vaccine development for Tasmanian devil conservation.
The Wnt1-Cre2 transgene causes aberrant recombination in non-neural crest cell types
Authors: Gandhi Shashank , Du Emily J. , Pangilinan Edivinia S. , Harland Richard M.
Published: November 2024

The Wnt1-Cre2 driver, designed to address the effect of Wnt1 overactivation in the ventral neural tube in the original Wnt1-Cre line, was recently shown to have ectopic expression in the male germline. When crossed with a reporter mouse, we observed fluorescent protein expression in non-neural-crest cell types in the gut. Here, we characterize the pattern of Cre-mediated recombination in the Wnt1-Cre2 driver using three transgenic reporter lines. We find aberrant reporter activation in the gut endoderm in embryonic and postnatal timepoints, starting as early as E8.5. This pattern of recombination was independent of the age, sex, and type of reporter line used, with the Wnt1-Cre2 allele inherited from either sires or dams resulting in ectopic fluorescence in the intestinal epithelium. We also detect reporter activity in the ventral neural tube. However, expression in the neural crest and its derivatives remained consistent with previous studies. We further quantify differences in the non-specific recombination observed across reporter lines using flow cytometry. Interestingly, the penetrance of reporter activation between reporter lines was different, with R26RmTmGshowing less ectopic activation than the R26RtdTomand R26ReYFPlines. Finally, we propose a potential mechanism whereby genes surrounding the Wnt1-Cre2 insertion site on mouse chromosome 2 contribute to its Wnt1-independent activation in the endoderm. Taken together, our results suggest that users should exercise caution when using the Wnt1-Cre2 driver line for neural crest studies in the mouse.
Estimating behavioural relaxation induced by COVID-19 vaccines in the first months of their rollout
Authors: Li Yuhan , Gozzi Nicolò , Perra Nicola
Published: November 2024

The initial rollout of COVID-19 vaccines has been challenged by logistical issues, limited availability of doses, scarce healthcare capacity, spotty acceptance, and variants of concern. Non-pharmaceutical interventions (NPIs) have been critical to support these phases. However, vaccines may have prompted behavioural relaxation, potentially reducing NPIs adherence. Epidemic models have explored this phenomenon, but they have not been validated against data. Moreover, recent surveys provide conflicting results on the matter. The extent of behavioural relaxation induced by COVID-19 vaccines is still unclear. Here, we aim to study this phenomenon in four regions. We implement five realistic epidemic models which include age structure, multiple virus strains, NPIs, and vaccinations. One of the models acts as a baseline, while the others extend it including different behavioural relaxation mechanisms. First, we calibrate the baseline model and run counterfactual scenarios to quantify the impact of vaccinations and NPIs. Our results confirm the critical role of both in reducing infection and mortality rates. Second, we calibrate the behavioural models and compare them to each other and to the baseline using different metrics. Including behavioural relaxation leads to a better fit of weekly deaths in three regions. However, the improvements are limited to a 2 − 10% reduction in weighted mean absolute percentage errors and these gains are generally offset by models’ increased complexity. Overall, we do not find clear signs of behavioural relaxation induced by COVID-19 vaccines on weekly deaths. Furthermore, our results suggest that if this phenomenon occurred, it generally involved only a firm minority of the population. Our work contributes to the retrospective validation of epidemic models developed amid the COVID-19 Pandemic and underscores the issue of non-identifiability of complex social mechanisms.
Viscous tweezers: Controlling particles with viscosity
Authors: Khain Tali , Fruchart Michel , Vitelli Vincenzo
Published: November 2024

Control of particle motion is generally achieved by applying an external field that acts directly on each particle. Here, we propose a global way to manipulate the motion of a particle by dynamically changing the properties of the fluid in which it is immersed. We exemplify this principle by considering a small particle sinking in an anisotropic fluid whose viscosity depends on the shear axis. In the Stokes regime, the motion of an immersed object is fully determined by the viscosity of the fluid through the mobility matrix, which we explicitly compute for a pushpin-shaped particle. Rather than falling upright under the force of gravity, as in an isotropic fluid, the pushpin tilts to the side, sedimenting at an angle determined by the viscosity anisotropy axis. By changing this axis, we demonstrate control over the pushpin orientation as it sinks, even in the presence of noise, using a closed feedback loop. This strategy to control particle motion, that we dub viscous tweezers, could be experimentally realized in systems ranging from polyatomic fluids under external fields to chiral active fluids of spinning particles by suitably changing their direction of global alignment or anisotropy.

Published by the American Physical Society
2024
Evidence of Zero-Field Wigner Solids in Ultrathin Films of Cadmium Arsenide
Authors: Munyan Simon , Ahadi Sina , Guo Binghao , Rashidi Arman , Stemmer Susanne
Published: November 2024

The quantum Wigner crystal is a many-body state where Coulombic repulsion quenches the kinetic energy of electrons, causing them to crystallize into a lattice. Experimental realization of a quantum Wigner crystal at zero magnetic field has been a long-sought goal. Here, we report on the experimental evidence of a Wigner solid in ultra-thin films of cadmium arsenide (Cd3As2) at zero magnetic field. We show that a finite bias depins the domains and produces an unusually sharp-threshold current-voltage behavior. Hysteresis and voltage fluctuations point to domain motion across the pinning potential and disappear at finite temperature as thermal fluctuations overcome the potential. The application of a small magnetic field destroys the Wigner solid, pointing to an unconventional origin. We use Landau-level spectroscopy to show that the formation of the Wigner solid is closely connected to a topological transition as the film thickness is reduced.

Published by the American Physical Society
2024
Impact of customer relationship management, financial literacy and social influence on online banking adoption: the moderating role of personal innovativeness
Authors: Asif Muhammad , Sarwar Farhan
Published: November 2024

Purpose

This research used the technology acceptance model (TAM) to explore the effect of customer relationship management, financial literacy and social influence on users’ intentions to adopt online banking. Furthermore, it explores the moderating role of personal innovativeness in technology in this context.

Design/methodology/approach

The measuring scale in this study was refined iteratively through talks with domain experts. A digital survey was used to gather data from 524 respondents, and PLS-SEM was used for analysis.

Findings

The findings reveal that customer relationship management and financial literacy significantly impact perceived usefulness and perceived ease of use but not the intention to adopt online banking. Perceived usefulness and perceived ease of use significantly influence intention, whereas personal innovativeness and social influence do not. Additionally, the moderation effects of personal innovativeness between customer relationship management, financial literacy, social influence and intention are insignificant.

Originality/value

This innovative study introduces personal innovativeness in technology as a moderator in the perspective of online banking adoption, setting new standards in the field. This important point has not been covered in previous studies.
Daily vulnerability and disaster resilience: a case study of preferred community assets and social capital for Latinx coastal residents
Authors: Blockstein Joshua , Tilt Jenna H. , Botello Salgado Beatriz
Published: November 2024

Purpose

This study explores how marginalized populations in high-hazard-risk areas on the Oregon coast utilize valued locations and social networks to adapt to daily challenges and natural hazards.

Design/methodology/approach

We hypothesize that locations most valued for their associated resources (community assets) also support the most social capital. Focus group discussions and a novel conceptual mapping activity were employed to identify preferred community assets and associated social capital for Latinx residents.

Findings

Community-based organizations, churches and schools are the preferred community assets found to enable strong social capital, although differences existed in which forms of structural social capital were identified. Mechanisms by which relationships are formed in this case study and implications for disaster resilience are discussed and theoretically linked to other relevant contexts.

Research limitations/implications

We provide policy recommendations to utilize community assets and social capital to support disaster resilience for marginalized populations.

Originality/value

Recruitment of participants through a community-engaged process developed trust with Latinx community members. Focus group design addressed barriers to participation to create space for diverse perspectives. By applying social capital theory to this data, actionable insights are identified to better incorporate the values and needs of marginalized groups into disaster risk reduction efforts.
Who came first, the egg or the chicken? What comes first, psychological contract breach or perceived job insecurity?
Authors: Junça Silva Ana , López Sergio
Published: November 2024

Purpose

This study uses a job-demand resource perspective to test a conceptual model in which psychological contract breach has a negative relation with job performance (adaptivity and proficiency) through perceived job insecurity. Further, it has also been proposed that higher levels of role conflict will strengthen the impact of psychological contract breaches on job performance through job insecurity.

Design/methodology/approach

Two-wave data were collected from 449 working adults from the retail sector with managerial occupations in Chile. The moderated mediation models were tested through SPSS macro (developed by Preacher and Hayes, 2004).

Findings

The findings supported the hypotheses; first, psychological contract breach negatively influences job performance through job insecurity; and second, role conflict moderates the indirect relationship in a way that lower levels of role conflict buffer the relationship between psychological contract breach and job performance through job insecurity (versus higher levels of role conflict).

Originality/value

This study has practical and theoretical implications. On the one hand, it establishes how and when psychological contract breaches might harm individual job performance. On the other hand, it can be a guide to managers and employees who can find evidence about how harmful a breach of employees’ psychological contract can be.
Images as data – modelling data interactions in social science and humanities research
Authors: Late Elina , Matres Inés , Sendra Anna , Kumpulainen Sanna
Published: November 2024

Purpose

The expanded reuse of images as research data in the social sciences and humanities necessitates the understanding of scholars’ real-life interactions with the type of data. The aim of this study is to analyse activities constituting image data interactions in social science and humanities research and to provide a model describing the data interaction process.

Design/methodology/approach

The study is based on interviews with 21 scholars from various academic backgrounds utilising digital and print images collected from external sources as empirical research data. Qualitative content analyses were executed to analyse image data interactions throughout the research process in three task types: contemporary, historical and computational research.

Findings

The findings further develop the task-based information interaction model (Järvelin et al., 2015) originally created to explain the information interaction process. The enhanced model presents five main image data interaction activities: Data gathering, Forming dataset, Working with data, Synthesizing and reporting and Concluding, with various sub-activities. The findings show the variety of image data interactions in different task types.

Originality/value

The developed model contributes to understanding critical points in image data interactions and provides a model for future research analysing research data interactions. The model may also be used, for example, in designing better research services and infrastructures by identifying support needs throughout the research process.
There is nothing like staying at home: Japanese employees’ dispositional resistance to change and their expatriation willingness
Authors: Yamao Sachiko , Sekiguchi Tomoki
Published: November 2024

Purpose

This study examines how dispositional resistance to change (DRTC) – a change-specific personality trait – affects the expatriation willingness of Japanese employees in multinational corporations (MNCs) headquartered in Japan. We theorize that DRTC affects expatriation willingness through two situationally relevant mediators (motivational cultural intelligence (CQ) and foreign language anxiety) to discover ways in which organizations can change their employees’ attitudes for them to be willing to expatriate.

Design/methodology/approach

We tested mediation hypotheses using a two-wave survey of 693 Japanese MNC employees in various industries. Data were analyzed with structural equation modeling using Mplus 8.

Findings

The results indicate that motivational CQ and foreign language anxiety fully mediate the negative relationship between DRTC and willingness to expatriate.

Originality/value

The current study offers insights into expatriation willingness by revealing that DRTC is a personality trait relevant to be studied in the expatriation context. Second, and more importantly, the study finds that motivational CQ and foreign language anxiety are crucial mechanisms through which DRTC influences expatriation willingness. This is important because the study reveals that MNCs can influence their employees’ career choices even if they cannot directly change their personality traits (i.e. DRTC).
Investigation of the effectiveness of the implementation of gender equality strategies: a case study of an Australian public sector organization in a male-dominated industry
Authors: Safari Maryam , Gekara Victor
Published: November 2024

Purpose

The purpose of this study is to investigate, through the application of a decoupling conceptual framework, why seemingly appropriate workplace gender strategies may not yield the desired results. In doing so, the authors address two key questions: how and why have seemingly comprehensive gender equality–related strategies failed to eradicate workplace gender inequality, and how can implementing these strategies be more effective?

Design/methodology/approach

The authors use a qualitative approach to examine a case study organization within the public sector. This involves a combination of document analysis, semistructured interviews and focus groups. The authors use a unique data set to investigate the effectiveness of implementing a socially oriented strategy related to gender equality.

Findings

The findings highlight different approaches in the implementation of gender equality strategies compared to those aligned with core business objectives. This study also identifies techniques for bridging the gender equality strategy–practice gap, offering significant implications for both policy and practice.

Research limitations/implications

This research is subject to common limitations associated with case studies, interviews and focus groups.

Originality/value

Despite the growing awareness and increased focus on eliminating workplace gender inequality, it remains a “wicked problem” due to its global pervasiveness and the complexity of its causes, manifestations and implications. This issue continues to present itself in various forms across numerous sectors and organizations, despite decades of concerted efforts by multiple stakeholders, including governments, nongovernmental organizations, businesses and society at large. In this paper, the authors investigate the reasons for such slow progress and argue that this issue is less related to the appropriateness of existing gender strategies and more a result of the ineffective implementation of these strategies.