bluuebunny/crossref_metadata_2025 huggingface dataset:
Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T
Authors: Read Marie-Lucie , Berry Samuel C. , Graham Kim S. , Voets Natalie L. , Zhang Jiaxiang , Aggleton John P. , Lawrence Andrew D. , Hodgetts Carl J.
Published: October 2023

Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category sensitivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside retrosplenial and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus.
Evolution of research topics and paradigms in plant sciences
Authors: Shiu Shin-Han , Lehti-Shiu Melissa D.
Published: October 2023

Scientific advances due to conceptual or technological innovations can be revealed by examining how research topics have evolved. But such topical evolution is difficult to uncover and quantify because of the large body of literature and the needs of expert knowledge from a wide range of areas in any field. Here we used machine learning and language models to classify plant science citations into topics representing interconnected, evolving subfields. The changes in prevalence of topical records over the last 50 years reflect major research paradigm shifts and recent radiation of new topics, as well as turnovers of model species and vastly different plant science research trajectories among countries. Our approaches readily summarize the topical diversity and evolution of a scientific field with hundreds of thousands of relevant papers, and they can be applied broadly to other fields.

Significance statement

Changes in scientific paradigms are foundational for the advancement of science, but such changes are difficult to summarize, quantify, and illustrate. These challenges are exacerbated by the rapid, exponential growth of literature. Applying a combination of machine learning and language modeling to hundreds of thousands of published abstracts, we demonstrate that a scientific field (i.e., plant science) can be summarized as interconnected subfields evolving from one another. We also reveal insights into major research trends and the rise and decline in the use of model organisms in different countries. Our study demonstrates how artificial intelligence and language models can be broadly applied to understand scientific advances that inform science policy and funding decisions.
Evolution of olfactory sensitivity, preferences and behavioral responses in Mexican cavefish: fish personality matters
Authors: Blin Maryline , Valay Louis , Kuratko Manon , Pavie Marie , Rétaux Sylvie
Published: October 2023

Animals are adapted to their natural habitats and lifestyles. Their brains perceive the external worldviatheir sensory systems, compute information together with that of internal states and autonomous activity, and generate appropriate behavioral outputs. However, how do these processes evolve across evolution? Here, focusing on the sense of olfaction, we have studied the evolution in olfactory sensitivity, preferences and behavioral responses to six different food-related amino acid odors in the two eco-morphs of the fishAstyanax mexicanus. To this end, we have developed a high-throughput behavioral setup and pipeline of quantitative and qualitative behavior analysis, and we have tested 489 six-week-oldAstyanaxlarvae. The blind, dark-adapted morphs of the species showed markedly distinct basal swimming patterns and behavioral responses to odors, higher olfactory sensitivity and a strong preference for alanine, as compared to their river-dwelling eyed conspecifics. In addition, we discovered that fish have an individual “swimming personality”, and that this personality influences their capability to respond efficiently to odors and find the source. Importantly, the personality traits that favored significant responses to odors were different in surface fish and cavefish. Moreover, the responses displayed by second-generation cave x surface F2 hybrids suggested that olfactory-driven behavior and olfactory sensitivity is a quantitative genetic trait. Our findings show that olfactory processing has rapidly evolved in cavefish at several levels: detection threshold, odor preference, and foraging behavior strategy. Cavefish is therefore an outstanding model to understand the genetic, molecular and neurophysiological basis of sensory specialization in response to environmental change.
Identity and Nature of Neural Stem Cells in the Adult Human Subventricular Zone
Authors: Baig Salma , Nadaf Javad , Allache Redouane , Le Phuong U. , Luo Michael , Djedid Annisa , Safisamghabadi Maryam , Prat Alex , Antel Jack , Guiot Marie-Christine , Petrecca Kevin
Published: October 2023

The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early-lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.
Activity-Dependent Alternative Splicing of Adhesion-GPCR Latrophilin-3 Controls Synapse Formation
Authors: Wang Shuai , DeLeon Chelsea , Roth Bryan , Südhof Thomas C.
Published: October 2023

How synapses are assembled and specified in brain is incompletely understood. Latrophilin- 3, a postsynaptic adhesion-GPCR, mediates Schaffer-collateral synapse formation in the hippocampus but the mechanisms involved remained unclear. Here we show that Latrophilin-3 organizes synapses by a convergent dual-pathway mechanism by which Latrophilin-3 simultaneously activates GαS/cAMP-signaling and recruits phase-separated postsynaptic protein scaffolds. We found that cell type-specific alternative splicing of Latrophilin-3 controls its G protein coupling mode, resulting in Latrophilin-3 variants that predominantly signal via Gαsand cAMP or via Gα12/13. A CRISPR-mediated genetic switch of Latrophilin-3 alternative splicing from a GαS- to a Gα12/13-coupled mode impaired synaptic connectivity similar to the overall deletion of Latrophilin-3, suggesting that GαS/cAMP- signaling by Latrophilin-3 splice variants mediates synapse formation. Moreover, GαS- but not Gα12/13-coupled splice variants of Latrophilin-3 recruit phase-transitioned postsynaptic protein scaffolds that are clustered by binding of presynaptic Latrophilin-3 ligands. Strikingly, neuronal activity promotes alternative splicing of the synaptogenic variant of Latrophilin-3, thereby enhancing synaptic connectivity. Together, these data suggest that activity- dependent alternative splicing of a key synaptic adhesion molecule controls synapse formation by parallel activation of two convergent pathways, GαS/cAMP signaling and the phase separation of postsynaptic protein scaffolds.
Neuronal activity induces symmetry breaking in neurodegenerative disease spreading
Authors: Alexandersen Christoffer G. , Goriely Alain , Bick Christian
Published: October 2023

Dynamical systems on networks typically involve several dynamical processes evolving at different timescales. For instance, in Alzheimer’s disease, the spread of toxic protein throughout the brain not only disrupts neuronal activity but is also influenced by neuronal activity itself, establishing a feed-back loop between the fast neuronal activity and the slow protein spreading. Motivated by the case of Alzheimer’s disease, we study the multiple-timescale dynamics of a heterodimer spreading process on an adaptive network of Kuramoto oscillators. Using a minimal two-node model, we establish that heterogeneous oscillatory activity facilitates toxic outbreaks and induces symmetry breaking in the spreading patterns. We then extend the model formulation to larger networks and perform numerical simulations of the slow-fast dynamics on common network motifs and on the brain connectome. The simulations corroborate the findings from the minimal model, underscoring the significance of multiple-timescale dynamics in the modeling of neurodegenerative diseases.
Distinct learning, retention, and generalization in de novo learning
Authors: Gastrock Raphael Q. , ’t Hart Bernard Marius , Henriques Denise Y. P.
Published: October 2023

People correct for movement errors when acquiring new motor skills (de novo learning) or adapting well-known movements (motor adaptation). These two motor learning types should be distinct, as de novo learning establishes new control policies while adaptation modifies existing ones. Here, we distinguish between these two motor learning types, and assess de novo learning retention and generalization. In study 1, participants train with both 30° visuomotor rotation and mirror reversal perturbations, to compare adaptation and de novo learning respectively. We find no perturbation order effects, and that learning develops with similar rates and comparable asymptotes for both perturbations. Explicit instructions also provide an advantage during early learning in both perturbations. However, mirror reversal learning shows larger inter-participant variability. Furthermore, movement initiation is slower for the mirror perturbation, and we only observe reach aftereffects following rotation training. In study 2, we use a browser-based mirror reversal task to investigate learning retention and generalization to the untrained hand and across the workspace. Learning persists across three or more days, substantially transfers to the untrained hand, and to targets on both sides of the mirror axis. Our results show that behavioral mechanisms underlying motor skill acquisition are distinct from adapting well-known movements.
Circadian photoreceptor CRYPTOCHROME promotes wakefulness under short winter-like days via a GABAergic circuitry
Authors: Chen Lixia , Tian Danya , Su Chang , Zhang Luoying
Published: October 2023

A cardinal symptom of seasonal affective disorder (SAD, also known as winter depression) is hypersomnolence, while the cause of this “winter sleepiness” is not known. Here we found that lack of the circadian photoreceptorcryptochrome(cry) leads to increased sleep under short winter-like days in fruit flies, reminiscent of the hypersomnolence in SAD. CRY functions in neurons that synthesize the major inhibitory neurotransmitter GABA, including the small ventral lateral neurons which are known to be circadian pacemakers, and down-regulates the GABAergic tone. This in turn leads to increased neural activity of the wake-promoting large ventral lateral neurons, a subset of circadian neurons that are inhibited by GABA-A receptor. CRY protein is known to be degraded by light, thus rendering CRY to be functional within this GABAergic circuitry to enhance wakefulness only under short day length. Taken together, we demonstrate a mechanism that specifically regulates wakefulness under short winter-like days, which may provide insights regarding the winter sleepiness in SAD.
EEG markers of drowsiness do not predict lapses in attention during sleep deprivation
Authors: Snipes Sophia , Meier Elias , Accascina Simone , Huber Reto
Published: October 2023

During drowsiness, maintaining consistent attention becomes difficult, leading to behavioral lapses. Oscillation bursts in the electroencephalogram (EEG) might predict such lapses, since alpha bursts increase with inattention and theta bursts increase with time spent awake. However, while lapses increase with time awake, paradoxically alpha bursts decrease, and the behavioral relevance of theta bursts is unknown. Therefore, we investigated whether theta or alpha bursts predicted lapses either when well rested (baseline, BL) or sleep deprived (SD). EEG was measured in 18 young adults performing the lateralized attention task, and the timing of bursts was related to trial outcomes (fast, slow, and lapse trials). Against expectations, neither theta nor alpha bursts were more likely during lapses, either at BL or SD. Both were more likely before fast trials, but only at BL. Fast and slow trials were followed by decreases in both theta and alpha bursts, but the effect was reduced during SD, partially due to local increases in bursts. Considering prior literature, these results indicate that bursts have a non-linear relationship with vigilance. The lack of a direct relationship to lapses may be because bursts originate from task-unrelated areas, and the differences during SD suggest these areas change with time awake.
Lipopolysaccharides derived fromPorphyromonas gingivalisandEscherichia coli:differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TRL4-related processes
Authors: Saito Koji , Aono Yuri , Watanabe Arata , Kono Tetsuro , Hashizume-Takizawa Tomomi , Okada Hiroyuki , Kosuge Yasuhiro , Senpuku Hidenobu , Waddington John L. , Saigusa Tadashi
Published: October 2023

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs).Porphyromonas gingivalis(Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived fromEscherichia coli(Ec-LPS). However, whetherPg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects ofPg-LPS. For comparison, effects ofEc-LPS were also studied. We also investigated the influence of systemic administration ofPg-LPS orEc-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. SincePg-LPS may block TLR4in vitro, we analysed the effects ofPg-LPS onEc-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Compounds were administered intraperitoneally.Ec-LPS (840 µg/kg), but notPg-LPS (100, 500 and 840 µg/kg), inhibited novelty-induced locomotion, which was reversed by TAK-242 (3.0 mg/kg).Ec-LPS (840 µg/kg) increased blood levels of IL-6 and IL-10, which was antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibitEc-LPS-induced increases in TNF-alpha levels in blood.Pg-LPS (100, 500, and 840 µg/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. TheEc-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited byPg-LPS (500 µg/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration ofEc-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast,Pg-LPS did not exhibit these effects. The present study also providesin vivoevidence thatPg-LPS can inhibit TLR4-mediated increases in blood IL-10 levels, which is thought to prevent the development of periodontal disease.
Diffusion of activated ATM explains γH2AX and MDC1 spread beyond the DNA damage site
Authors: Danovski Georgi , Panova Greta , Keister Bradley , Georgiev Georgi , Blagoev Krastan B. , Stoynov Stoyno S.
Published: October 2023

During DNA repair, ATM-induced H2AX histone phosphorylation and MDC1 recruitment spread megabases beyond the damage site. The mechanism underlying this spread remains unclear. To elucidate this step of the DNA damage response, we measured ATM and MDC1 recruitment kinetics at micro-irradiation-induced complex DNA lesions. While MDC1 spreads beyond the damage-induced focus of ATM accumulation, cohesin loader NIPBL and cohesin subunit RAD21 accumulate later than MDC1. Such delayed recruitment suggests that, in complex DNA lesions, loop extrusion cannot alone explain γH2AX and MDC1 spread. To determine if diffusion of activated ATM could account for the observed behavior, we measured the exchange rate and diffusion constants of ATM and MDC1 within damaged and unperturbed chromatin. Based on these measurements, we introduced a quantitative model that describes the dynamic behavior of ATM and subsequent MDC1 spread at complex DNA lesions. Altogether, we propose activated ATM diffusion as an underlying mechanism of MDC1 spread.
Non-canonical activation of IRE1α duringCandida albicansinfection enhances macrophage fungicidal activity
Authors: McFadden Michael J. , Reynolds Mack B. , Michmerhuizen Britton C , Ólafsson Einar B. , Anderson Faith M. , Schultz Tracey L. , O’Riordan Mary X.D. , O’Meara Teresa R.
Published: October 2023

While the canonical function of IRE1α is to detect misfolded proteins and activate the unfolded protein response (UPR) to maintain cellular homeostasis, microbial pathogens can also activate IRE1α, which modulates innate immunity and infection outcomes. However, how infection activates IRE1α and its associated inflammatory functions have not been fully elucidated. Recognition of microbe-associated molecular patterns can activate IRE1α, but it is unclear whether this depends on protein misfolding. Here, we report that a common and deadly fungal pathogen,Candida albicans, activates macrophage IRE1α through C-type lectin receptor signaling, reinforcing a role for IRE1α as a central regulator of host responses to infection by a broad range of pathogens. This activation did not depend on protein misfolding in response toC. albicansinfection. Moreover, lipopolysaccharide treatment was also able to activate IRE1α prior to protein misfolding, suggesting that pathogen-mediated activation of IRE1α occurs through non-canonical mechanisms. DuringC. albicansinfection, we observed that IRE1α activity promotes phagolysosomal fusion that supports the fungicidal activity of macrophages. Consequently, macrophages lacking IRE1α activity displayed inefficient phagosome maturation, enablingC. albicansto lyse the phagosome, evade fungal killing, and drive aberrant inflammatory cytokine production. Mechanistically, we show that IRE1α activity supports phagosomal calcium flux after phagocytosis ofC. albicans, which is crucial for phagosome maturation. Importantly, deletion of IRE1α activity decreased the fungicidal activity of phagocytesin vivoduring systemicC. albicansinfection. Together, these data provide mechanistic insight for the non-canonical activation of IRE1α during infection, and reveal central roles for IRE1α in macrophage antifungal responses.
Differential Chromatin Architecture and Risk Variants in Deep Layer Excitatory Neurons and Grey Matter Microglia Contribute to Major Depressive Disorder
Authors: Chawla Anjali , Cakmakci Doruk , Zhang Wenmin , Maitra Malosree , Rahimian Reza , Mitsuhashi Haruka , Davoli MA , Yang Jenny , Chen Gary Gang , Denniston Ryan , Mash Deborah , Mechawar Naguib , Suderman Matthew , Li Yue , Nagy Corina , Turecki Gustavo
Published: October 2023

Major depressive disorder (MDD) associated genetic variants reside primarily in the non-coding, regulatory genome. Here we investigate genome-wide regulatory differences and putative gene-regulatory effects of disease risk-variants by examining chromatin accessibility combined with single-cell gene-expression profiles in over 200,000 cells from the dorsolateral prefrontal cortex (DLPFC) of 84 individuals with MDD and neurotypical controls. MDD-associated accessibility alterations were prominent in deep-layer excitatory neurons characterized by transcription factor (TF) motif accessibility and binding of nuclear receptor (NR)4A2, an activity-dependent TF responsive to pathological stress. The same neurons were significantly enriched for MDD-associated genetic variation disrupting cis-regulatory sites and TF binding associated with genes involved in synaptic communication. Furthermore, a grey matter microglial cluster exhibited differentially closed chromatin in MDD affecting binding sites bound by TFs known to regulate immune homeostasis. In summary, our study points to specific cell types and regulatory mechanisms whereby genetic variation may increase predisposition to MDD.
Asymmetric cortical projections to striatal direct and indirect pathways distinctly control actions
Authors: Klug Jason R. , Yan Xunyi , Hoffman Hilary A. , Engelhardt Max D. , Osakada Fumitaka , Callaway Edward M. , Jin Xin
Published: October 2023

The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a new G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do sovice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry.

In Brief

Klug, Yan et al. employed a new modified rabies system in combination with slice physiology, optogenetics and behavioral tests to reveal that pathway-specific corticostriatal subcircuits distinctly control actions.

Highlights

One-third of the excitatory inputs to D1-SPNs project to D2-SPNs, while two-third of the excitatory inputs to D2-SPNs also target D1-SPNs

Activation of D1-SPN projecting cortical neurons triggers behavioral effects in line with postsynaptic striatal direct pathway activation

Activation of D2-SPN projecting cortical neurons causes behavioral effects similar with co-activation of both direct and indirect pathways

Corticostriatal subcircuits control actions in a brain-region and pathway-specific manner
Predicting individualized treatment effects of corticosteroids in community-acquired-pneumonia: a data-driven analysis of randomized controlled trials
Authors: Smit J.M. , Van Der Zee P.A. , Stoof S.C.M. , Van Genderen M.E. , Snijders D. , Boersma W. G. , Confalonieri P. , Salton F. , Confalonieri M. , Shih M-C. , Meduri G.U. , Dequin P.-F. , Le Gouge A. , Lloyd M. , Karunajeewa H. , Bartminski G. , Fernández-Serrano S. , Suárez-Cuartín G. , van Klaveren D. , Briel M. , Schoenenberger C.M. , Steyerberg E.W. , Gommers D.A.M.P.J. , Bax H.I. , Bos W J. W. , Van De Garde E.M.W. , Wittermans E. , Grutters J.C. , Blum C.A. , Christ-Crain M. , Torres A. , Motos A. , Reinders M.J.T. , Van Bommel J. , Krijthe J.H. , Endeman H.
Published: October 2023

Background

Corticosteroids could improve outcomes in patients with community-acquired pneumonia (CAP). However, we hypothesize that corticosteroid effectiveness varies among individual patients, resulting in inconsistent outcomes and unclear clinical indication. Therefore, we developed and validated a predictive, causal model based on baseline characteristics to predict individualized treatment effects (ITEs) of corticosteroids on mortality in patients with CAP.

Methods

We obtained individual patient data from six randomized controlled trials comparing corticosteroid therapy to placebo in 1,869 adult CAP patients. The study endpoint was 30-day mortality. We performed effect modelling through logistic regression and evaluated the predicted ITEs in terms of discrimination and calibration for benefit. Our modelling procedure involved variable selection, missing value imputation, data normalization, encoding treatment variables, creating interaction terms, optimizing penalization strength, and training logistic regression models. We evaluated discriminative performance using the newly proposed ‘AUC-benefit’.

Findings

The model identified high levels of CRP and glucose, at baseline, as main predictors for benefit of corticosteroid treatment. Using a decision threshold of ITE=0, the model predicted harm in 1,004 patient and benefit in 864 patients. We observed benefit in patients where the model predicted benefit, with an odds ratio of 0.5 (95% CI: 0.3 to 0.9) and a mortality reduction of 3.2% (95% CI: 0.7 to 5.6), and no statistically significant benefit in the patients where the model predicted harm, with an odds ratio of 1.1 (95% CI: 0.7 to 1.8) and a negative mortality reduction (hence, increase) of −0.3% (95% CI: −2.6 to 1.8). The model yielded an AUC-benefit of 184.9 (28.6 to 347.6, 95% CI), underestimated ITEs in the lower ITE region and slightly overestimated ITEs in the higher ITE region.

Interpretation

Our model has potential to identify patients with CAP who benefit from corticosteroid treatment, and aid in the design of personalized clinical trials. We will prospectively validate the model in two recent CAP trials.
Colchicine promotes atherosclerotic plaque stability independently of inflammation
Authors: Li Weizhen , Lin Alexander , Hutton Michael , Dhaliwal Harkirat , Nadel James , Rodor Julie , Tumanov Sergey , Örd Tiit , Hadden Matthew , Mokry Michal , Mol Barend M , Pasterkamp Gerard , Padula Matthew P , Geczy Carolyn L , Ramaswamy Yogambha , Sluimer Judith C , Kaikkonen Minna U , Stocker Roland , Baker Andrew H , Fisher Edward A , Patel Sanjay , Misra Ashish
Published: October 2023

Atherosclerosis is a chronic inflammatory disease which is driven in part by the aberranttrans-differentiation of vascular smooth muscle cells (SMCs). No therapeutic drug has been shown to reverse detrimental SMC-derived cell phenotypes into protective phenotypes, a hypothesized enabler of plaque regression and improved patient outcome. Herein, we describe a novel function of colchicine in the beneficial modulation of SMC-derived cell phenotype, independent of its conventional anti-inflammatory effects. Using SMC fate mapping in an advanced atherosclerotic lesion model, colchicine induced plaque regression by converting pathogenic SMC-derived macrophage-like and osteoblast-like cells into protective myofibroblast-like cells which thickened, and thereby stabilized, the fibrous cap. This was dependent on Notch3 signaling in SMC-derived plaque cells. These findings may help explain the success of colchicine in clinical trials relative to other anti-inflammatory drugs. Thus, we demonstrate the potential of regulating SMC phenotype in advanced plaque regression through Notch3 signaling, in addition to the canonical anti-inflammatory actions of drugs to treat atherosclerosis.
M1-derived extracellular vesicles polarize recipient macrophages into M2 and alter skeletal muscle homeostasis in a hyper-glucose environment
Authors: Tacconi Stefano , Vari Francesco , Sbarigia Carolina , Vardanyan Diana , Longo Serena , Mura Francesco , Angilè Federica , Jalabart Audrey , Vergara Daniele , Fanizzi Francesco Paolo , Rossi Marco , Errazuriz-Cerda Elizabeth , Cassin Christel , Nieuwland Rienk , Giudetti Anna Maria , Rome Sophie , Dini Luciana
Published: October 2023

Background

Macrophages release not only cytokines but also extracellular vesicles (EVs). EVs are small lipid-derived vesicles with virus-like properties transferring lipids, RNA and proteins between cells. Until now, the consequences of macrophage plasticity on the release and the composition of EVs have been poorly explored. In this study, we determined the impact of high-glucose (HG) concentrations on macrophage metabolism, and characterized their derived EV subpopulations. Finally, we determined whether HG-treated macrophage-derived EVs participate in immune responses and in metabolic alterations of skeletal muscle cells.

Methods

THP1-macrophages (M0) were treated with 15mM (MG15) or 30mM (MG30) glucose. M1 or M2 canonical markers, pro– and anti-inflammatory cytokines and lactate production were evaluated. Macrophage-derived EVs were characterized by TEM, flow cytometry, and 1H-Nuclear magnetic resonance spectroscopy for lipid composition. M0 macrophages or C2C12 muscle cells were used as recipients of MG15 and MG30-derived EVs. The lipid profiles of recipient cells were determined, as well as protein and mRNA levels of relevant genes for macrophage polarization or muscle metabolism.

Results

M0 released 2 populations of small and large EVs (sEVs, lEVs) with specific lipid profiles. Proportionally to the glucose concentration, glucose-treatment induced glycolysis in M0 macrophages which consequently shifted into a pro-inflammatory M1 phenotype, containing increased triacylglycerol and cholesterol content. Glucose also affected macrophage sphingolipid and phospholipid compositions. The lipid profile differences between sEVs and lEVs were abolished and represented the lipid profile alterations of MG15 and MG30 macrophages. Both sEVs and lEVs from M15 and M30 macrophages polarized M0 into anti-inflammatory M2, with increased contents of triacylglycerol and cholesterol. MG15 lEVs and sEVs induced insulin-induced AKT hyper-phosphorylation and accumulation of triacylglycerol in muscle cells, a state observed in pre-diabetes. Conversely, MG30 lEVs and sEVs induced insulin resistance in myotubes.

Conclusions

As inflammation involves first M1 macrophages, then the activation of M2 macrophages to attenuate inflammation, this study demonstrates that the dialog between macrophages through the EV route is an intrinsic part of the inflammatory response. In a hyperglycemic context, EV macrophages could participate in the development of muscle insulin-resistance and chronic inflammation.
Methods for Exploring the Circuit Basis of Ethanol-Induced Changes inDrosophilaGroup Locomotor Activity
Authors: Nuñez Kavin M. , Catalano Jamie L. , Scaplen Kristin M. , Kaun Karla R.
Published: October 2023

Locomotion is a behavioral readout that can be used to understand responses to specific stimuli or perturbations. The fly Group Activity Monitor (flyGrAM) provides a high-throughput and high-content readout of the acute stimulatory and sedative effects of ethanol. The flyGrAM system is adaptable and seamlessly introduces thermogenetic or optogenetic stimulation to dissect neural circuits underlying behavior and tests responses to other volatilized stimuli (humidified air, odorants, anesthetics, vaporized drugs of abuse, etc.). The automated quantification and readout of activity provide users with a real-time representation of the group activity within each chamber throughout the experiment, helping users to quickly determine proper ethanol doses and duration, run behavioral screens, and plan follow-up experiments.
Quantifying Mosquito Attraction Behavior Using Olfactometry
Authors: Castillo John S. , Bellantuono Anthony J. , DeGennaro Matthew
Published: October 2023

When blood feeding from human hosts, female mosquitoes can transmit life-threatening pathogens to humans, including dengue virus, chikungunya virus, and Zika virus. Olfaction is the primary sense mosquitoes use to locate and differentiate hosts and studying it can lead to new strategies to reduce the risk of disease. To effectively study host-seeking behavior in mosquitoes, a repeatable, quantitative assay that isolates olfaction from other cues is critical for interpreting mosquito behavior. Here, we contribute an overview of methods and best practices for the study of mosquito attraction (or lack thereof) by using olfactometry to quantify behavior. In the accompanying protocols, we present an olfactory-based behavioral assay using a uniport olfactometer that measures mosquito attraction rate to specific stimuli. We include construction details, setup of the uniport olfactometer, details of the behavioral assay, and data analysis guidelines, as well as how to prepare the mosquitoes before their introduction into the olfactometer. This uniport olfactometer behavioral assay is currently one of the most reliable methods to study mosquito attraction to a single olfactory stimulus.
Poly[[[μ-1,4-bis(pyridin-4-ylmethyl)piperazine][μ-4-(2-carboxylatoethyl)benzoato]copper(II)] monohydrate], a coordination polymer with twofold interpenetrated cds topology networks
Authors: Gaskin Gabrielle J. , LaDuca Robert L.
Published: October 2023

The title compound, {[Cu(C10H8O4)(C16H20N4)]·H2O}
n
, contains square-planar coordinated CuII ions linked by 4-(carboxylatoethyl)benzoato (ceb) and 1,4-bis(pyridin-4-ylmethyl)piperazine (bpmp) ligands into a tri-periodic coordination polymer with twofold interpenetrating 658 cds topology. Positional crystallographic disorder among the copper atoms, the ethylcarboxy group of the ceb ligands, and the water molecules of crystallization exists in a refined 0.655 (6)/0.345 (6) ratio.
Asian Paints: a valuation dilemma
Authors: Chaudhury Arit , Dawar Varun
Published: October 2023

Learning outcomes

This case study will allow students to understand and analyse the process for conducting equity valuation by building a three-statement financial model, to understand and apply the workings of discounted cash flow (DCF) valuation methodology and its components, to apply the concepts related to the calculation of the weighted average cost of capital in the determination of discounting rate, to understand the terminal value calculation and assumptions thereof and to analyse the intrinsic valuation for the target company using the traditional multi-stage DCF model for investment decision-making.

Case overview/synopsis

In July 2019, Kapil Agarwal, an equity analyst operating out of Mumbai, India, was carefully looking over the financials of Asian Paints, a leading paints company in India. As an equity analyst, Kapil was constantly on the lookout for fundamentally strong but undervalued companies that could create long-term wealth for his equity fund. To decide upon the right valuation of Asian Paints, Kapil conducted fundamental analysis using the DCF method on the basis of available financial information. This case study puts students in an investment analyst role wherein they forecast financial statements and conduct DCF valuation for Asian Paints to discover potentially undervalued stocks for investment decision-making.

Complexity academic level

This case study is designed for use in an undergraduate or postgraduate programme in business management, particularly in a course on business valuation or investment management or security analysis.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.
Accounting information quality and cash holdings—Moderating effects based on state ownerships and local appointments
Authors: Zhu Liangyu , Sun Yulong
Published: October 2023

Purpose

The purpose of this study is to explore the continuity and stability of the impact of accounting information quality on cash holdings, and the moderating effect of this relationship on state ownerships and local appointments.

Design/methodology/approach

Based on China's companies from 2011 to 2019, the authors divided cross-section and panel samples, adopted a linear and classification model and performed grouping regression.

Findings

The authors find that: first, the quality of corporate accounting information can significantly improve the level of cash holding, giving play to the strategic value effect of cash holding. But that boost is based on economies being able to solve agency problems. Second, the reduction of earnings management and the improvement of accounting information quality of NSOEs improve the level of cash holdings, while SOEs are on the contrary. Third, local appointments can play to the emotional strengths of their hometowns and play a synergistic role in this relationship, but the supervision effect of remote appointments is not obvious.

Originality/value

Through endogeneity and other tests, the conclusion is robust. Based on the agency and information asymmetry theory, the authors considered China's institutional and cultural factors, optimized accounting information's measurement and expanded the research boundary of the accounting field. The authors believe that applicable scenarios should be fully considered in the concluding relationship between accounting information quality and cash holdings. Enterprises should give full play to the advantages of cash holdings in strategic decision-making and financial efficiency, improve the quality of accounting information and also consider state ownerships and the differences in directors' emotions to reduce internal agency costs.
Actor roles emergence through actor engagement: an SD logic perspective
Authors: Wajid Anees , Paracha Osman Sadiq , Raziq Muhammad Mustafa
Published: October 2023

Purpose

Emergence is a key concept in service-dominant (SD) logic; however, the literature is neonatal on the underlying mechanisms that lead to emergence within service ecosystems. This study aims to address the call by Vargo et al. (2022) for understanding the role of actor engagement in emergence of novel outcomes, by identifying a process of how various actor roles in entrepreneurial ecosystem (EE) emerge as resource through the actor engagement.

Design/methodology/approach

Following a longitudinal design, this study conduct interviews from 20 respondents over eight months in three phases (group interviews, post-training, post-funding). This study analyzes the respondents’ engagement in an entrepreneurial service context. This study uses qualitative inductive approach and thematic analysis.

Findings

Results show that actor roles emerge as role expectations from essential provider and beneficiary position in a service ecosystem through actor role readiness, manifested as engagement properties in the actor engagement process. This study identifies five actor roles and their corresponding role readiness dimensions that emerge. Based on these propositions through which the authors position generic actor roles emergence within the actor engagement process in a service ecosystem.

Originality/value

This paper advances the understanding of micro-level process in emergence literature in SD logic by providing a conceptual understanding of emergence of actor roles as a resource through actor engagement. By grounding the study in EE, this study provides empirical evidence to the underlying mechanisms at the micro level of resource emergence process in a service ecosystem.
Cashless Vietnam: a study on intention and adoption of cashless payment
Authors: Dieu Huynh Thi My , Al Mamun Abdullah , Nguyen Thi Le Huyen , Naznen Farzana
Published: October 2023

Purpose

This study aims to identify factors that affect the intention and actual adoption of cashless payment (ACP) among Vietnamese youths. Extending the unified theory of acceptance and use of technology (UTAUT) model with two impelling factors (perceived trust [PTR] and lifestyle compatibility [LCM]), this study also examined the mediating effect of intention to adopt cashless payment (ICP) on the relationships of UTAUT model components with the actual ACP.

Design/methodology/approach

All data were collected online from 422 Vietnamese youths through online survey, and partial least squares structural equation modelling was performed to analyse the data.

Findings

The study’s results illustrated the positive and significant effects of performance expectancy, effort expectancy, facilitating conditions, LCM and PTR on ICP. However, social influence was found to exhibit a negative effect on ICP. Furthermore, ICP was found to contribute no mediation effects on the relationships of any of the components with the actual ACP.

Practical implications

This study’s findings are widely useful for marketers and managers to plot their promotional and campaigning strategies, emphasising factors that motivate consumers to adopt cashless payment. The obtained findings also benefit architects and designers in designing products and services by consolidating lifestyle standards and other requirements of consumers. Policymakers should implement policies and strategies to enforce rules and educate the public to widely adopt cashless payment across various sectors.

Originality/value

This study extended the UTAUT model with two new variables, i.e. PTR and LCM.
Circ_0026579 knockdown ameliorates lipopolysaccharide‐induced human lung fibroblast cell injury by regulating CXCR1 via miR‐370‐3p
Authors: Zhuang Yuanhong , Yang Yuyun , Peng Lihong
Published: October 2023

Pneumonia is an inflammatory disease in lower respiratory tracts and its development involves the regulation of RNAs. Circular RNAs are a class of RNA subgroups that can mediate the progression of pneumonia. However, the molecular mechanism of circ_0026579 in regulating pneumonia occurrence remains unclear. The study is designed to reveal the role of circ_0026579 in lipopolysaccharide (LPS)‐induced human lung fibroblast cell injury and the underlying mechanism. The expression levels of circ_0026579, miR‐370‐3p and C‐X‐C motif chemokine receptor 1 (CXCR1) were detected by quantitative real‐time polymerase chain reaction or by western blotting. The production of tumour necrosis factor‐α, interleukin (IL)‐1β and IL‐6 was assessed by enzyme‐linked immunosorbent assays. Malondialdehyde and superoxide dismutase levels were analysed using commercial kits. Cell viability, proliferation and apoptosis were analysed by cell counting kit‐8 assay, 5‐Ethynyl‐2′‐deoxyuridine assay and flow cytometry analysis, respectively. The binding relationship between miR‐370‐3p and circ_0026579 or CXCR1 was identified by dual‐luciferase reporter assay, RNA immunoprecipitation assay and RNA pull‐down assay. Circ_0026579 and CXCR1 expression were significantly upregulated, whereas miR‐370‐3p was downregulated in the serum of pneumonia patients. LPS treatment induced inflammatory response, oxidative stress and cell apoptosis and inhibited cell proliferation in MRC‐5 cells; however, these effects were reversed after circ_0026579 depletion. In terms of the mechanism, circ_0026579 acted as a miR‐370‐3p sponge, and miR‐370‐3p combined with CXCR1. Additionally, circ_0026579 depletion ameliorated LPS‐induced MRC‐5 cell disorder by increasing miR‐370‐3p expression. CXCR1 overexpression also relieved the miR‐370‐3p‐mediated effects in LPS‐treated MRC‐5 cells. Further, circ_0026579 induced CXCR1 expression by interacting with miR‐370‐3p. Circ_0026579 absence ameliorated MRC‐5 cell dysfunction induced by LPS through the regulation of the miR‐370‐3p/CXCR1 axis.
Community banks' capital requirements and regional housing tenure
Authors: Yang Chenzi , Moreira Fernando , Archibald Thomas Welsh
Published: October 2023

Bank capital requirements aim at reducing the likelihood of banks' failure. However, these policies may generate externalities on the overall economy. By investigating the pathways from capital requirements to housing tenure using structural equation modelling, we show that community banks' capital requirements increase the gap between the regional real estate loans‐based and non‐real estate loans‐based housing purchase rate and act as driving factors of housing market imbalance. The drop in residential real estate loans caused by the increase in capital requirements has two opposite effects: the direct effect motivates residents to rent properties, while the indirect effect motivates residents to purchase them due to the fall in housing prices. When both effects exist in housing purchases with real estate loans, the former effect is more influential than the latter one. Our findings suggest that the impact of capital requirements on housing tenure will depend on residents' reliance on real estate loans. If a housing purchase requires real estate loans, capital requirements will have a negative impact on the housing purchase, and vice versa.
Price predictability in liquid funds with illiquid underlying assets
Authors: Hughes William T. , Ling David C. , Ray Sugata , Xu Luqi
Published: October 2023

Daily‐priced real estate (DPRE) funds are designed to provide investors with daily liquidity while investing in illiquid private assets. DPRE fund returns are predictable, allowing for a trading strategy based on predicted returns to generate trading profits of 60–132 bps a year. Funds with higher predicted returns have higher investor flows, but the flow‐to‐future predicted performance relationship is no stronger for DPRE funds with higher return predictability than those with lower return predictability. This appears to be the result of trading constraints on highly predictable institutional DPRE funds. Even modest trading restrictions on monthly redemptions render profits from trading strategies based on return predictability economically insignificant.
A case report of extra‐articular manifestation of rheumatoid arthritis: Rheumatoid nodules in lungs
Authors: Bektyrganova Saltanat , Kozhakhmet Doskhan , Kim Alexey , Baigenzhin Abay , Togizbayev Galymzhan , Doszhan Ainur , Krivoruchkо Natalya , Pak Alexey , Peradze Manana , Sarsengaliyev Timur
Published: October 2023

Rheumatoid arthritis is a systemic inflammatory disorder primarily affecting joints but not limited to the joints alone. Extra‐articular manifestations involve skin, ocular, gastrointestinal, pulmonary, cardiac, renal, neurological, and hematological systems. Among them, skin manifestations (20%) are most common, presenting as nodules on the extensor surfaces of the upper and lower extremities. In rare cases these nodules can also be detected within the heart and lungs. Interestingly, rheumatoid nodules are often seen in patients on leflunomide, methotrexate, or tumor necrosis factor‐alpha antagonists. Nevertheless, definitive diagnosis requires a histopathological analysis. In this case report, we presented a 49‐year‐old male patient with a relatively short period of disease activity leading to rheumatoid nodules in the lungs. Considering the ongoing COVID‐19 pandemic and that tuberculosis was still endemic in Kazakhstan, achieving the definite diagnosis was challenging. Initial imaging study revealed bilateral polysegmental pneumonia. The tests for COVID‐19 and pulmonary tuberculosis were negative. A follow‐up chest computed tomography scan had signs of disseminated lung lesions of unknown origin. Lung biopsy showed a morphological picture of productive granulomas characteristic for tuberculosis. However, at the second look, typical scarring granulomas typically seen in rheumatoid nodules were observed.