bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of signaling fidelity between astrocyte endfeet and adjacent cerebral arterioles in an amyloid mouse model of Alzheimer’s disease
Authors: Weiss Blaine E. , Gant John C. , Lin Ruei-Lung , Gollihue Jenna L. , Kraner Susan D. , Rucker Edmund B. , Katsumata Yuriko , Jiang Yang , Nelson Peter T. , Wilcock Donna M. , Sompol Pradoldej , Thibault Olivier , Norris Christopher M.
Published: January 2025

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer’s disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two photon microscopy to investigate Ca2+signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake eight-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous Ca2+transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in response to air puff stimulation of contralateral whiskers) and concurrent Ca2+transients across astrocyte compartments were reduced in 5xFAD mice relative to WTs. Synchronous activity within multi-cell astrocyte networks was also impaired in the 5xFAD group. Using a custom application to assess functional coupling between astrocyte endfeet and immediately adjacent arteriole segments, we detected deficits in Ca2+response probability in 5xFAD mice. Moreover, endfeet Ca2+transients following arteriole dilations exhibited a slower onset, reduced amplitude, and lacked relative proportionality to vasomotive activity compared to WTs. The results reveal nuanced alterations in 5xFAD reactive astrocytes highlighted by impaired signaling fidelity between astrocyte endfeet and cerebral arterioles. The results have important implications for the mechanistic underpinnings of brain hypometabolism and the disruption of neurophysiological communication found in AD and other neurodegenerative conditions.

Significance

Astrocytes are an essential component of the neurovascular unit. Chronically reactive astrocyte phenotypes are mechanistically linked to deleterious features of Alzheimer’s disease (AD) including impaired cerebral blood flow, hypometabolism, and synapse dysfunction/loss. Here, we show that reactive astrocytes in a fully awake mouse model of AD-like amyloid pathology are spontaneously hyperactive, exhibit impaired functional connectivity, and respond to dilations in immediately adjacent arterioles with poor fidelity. The results reveal a key point of communication breakdown between the brain and the cerebrovasculature.
BuzzWatch: uncovering multi-scale temporal patterns in mosquito behavior through continuous long-term monitoring
Authors: Maire Théo , Wan Zhong , Lambrechts Louis , Hol Felix J.H.
Published: January 2025

Understanding the temporal dynamics of mosquito behavior is essential for developing effective interventions against pathogen transmission. However, limited knowledge exists about the environmental, physiological, and genetic factors influencing mosquito activity patterns. This knowledge gap is partly due to a lack of tools to accurately quantify the behavior of free-flying mosquitoes over extended periods. Here, we introduce BuzzWatch, an open-source, low-cost platform designed to continuously monitor mosquito flight behavior over several weeks with high temporal resolution. BuzzWatch records videos of mosquitoes freely flying in a transparent cage and automates the extraction, analysis, and visualization of behavioral data, including flight trajectories and population-level flight and sugar-feeding statistics. Using BuzzWatch, we quantified the daily rhythms of 10 Aedes aegypti populations from various geographic origins. Globally invasiveAe. aegyptishowed increased sugar feeding and flight activity during midday compared to native African populations. Our platform further revealed subtle, long-lasting effects of blood feeding on activity patterns and a complex response to extended daylight periods. By integrating a host-seeking module in BuzzWatch to deliver CO2and heat pulses, we observed a twofold increase inAe. aegypti’s response to host-associated cues during the daytime compared to nighttime. Combined, these results demonstrate BuzzWatch’s potential to investigate responses to host cues over seconds, natural variability in daily rhythms over hours, and phenotypic plasticity over days. BuzzWatch offers a novel perspective on mosquito behavior over multiple timescales, paving the way for advanced ecological and epidemiological studies that can inform targeted and effective vector control strategies.

Short Summary

This study introduces a new experimental platform to monitor multiple features of mosquito behavior (flight activity, sugar feeding, short range host-seeking) with high temporal resolution over several weeks.

Highlights

Continuous month-long tracking of mosquito flight activity in a laboratory setting.

Multiscale analysis of flight behavior, from seconds to weeks.

Mapping of natural variation in daily rhythm ofAedes aegyptipopulations.

Quantifying the long-lasting effect of physiological (blood-meal digestion) and environmental (photoperiod increase) perturbations.

Automatically monitoring response to short-range host-seeking cues at specific times of the day.
Transthyretin Levels and Instability in Alzheimer’s Disease: Correlations with AD Biomarkers in a Cohort Study
Authors: Gião Tiago , Tábuas-Pereira Miguel , Baldeiras Inês , Saavedra Joana , Dias Alexandre , Saraiva Maria João , Almeida Maria Rosário , Santana Isabel , Cardoso Isabel
Published: January 2025

Background

In the last few decades, Transthyretin (TTR) has gained attention due to its implication in brain functions and neurodegenerative conditions, such as Alzheimer’s Disease (AD) by modulating amyloid-beta (Aβ) pathology. This study aims to assess TTR levels and tetrameric instability in both plasma and cerebrospinal fluid (CSF) across the clinical continuum of AD, and to establish associations between TTR and key AD biomarkers, to enhance our understanding of the role of TTR in AD pathogenesis.

Methods

We conducted an evaluation of TTR levels and tetrameric instability in plasma and CSF in mild cognitive impairment (MCI-AD, n=29) and Dementia-AD (n=37) patients and examined the association with clinical, biochemical and genetic data.

Results

Key findings revealed a substantial decrease in plasma TTR levels in the Dementia-AD patients compared to the MCI-AD group, with a pronounced gender-specific effect identified in women, while no differences were detected in the CSF. The search for associations identified several correlations amongst MCI-AD patients where CSF TTR levels inversely correlated with markers of amyloid pathology and neurodegeneration such as Aβ40 (r=-0.43, p < 0.02), p-Tau181 (r=-0.54, p < 0.03), t-Tau (r=-0.57, p< 0.001) and NfL (r=-0.49, p<0.006). CSF TTR instability also correlated negatively with CSF Aβ42 (r=-0.6, p<0.001) and Aβ42/Aβ40 ratio (r=-0.58, p<0.001), indicating an association with increased amyloid burden. In the Dementia-AD group, plasma TTR levels correlated negatively with GFAP (r=-0.4, p<0.014), reflecting potential links with neuroinflammation. Additionally, plasma TTR instability correlated with CSF TTR instability (r=0.42, p < 0.009) and tau pathology markers (p-Tau181 (r=0.38, p < 0.02) and t-Tau (r=0.42, p<0.09)). Given the strong association between CSF TTR instability and Aβ42, we investigated the effect of the peptide on TTR tetrameric instability and showed a clear increase in TTR instability in samples incubated with Aβ42 for 24 hours (p<0.05).

Conclusions

This study emphasizes several associations between TTR and other key indicators of AD and suggests TTR is associated with Aβ clearance, neurodegeneration, and neuroinflammation across different stages of the disease. We propose Aβ42 and its increase in the brain as a factor destabilizing the TTR tetrameric fold, resulting in TTR impaired function.
Dietary protein restriction in rats leads to a rapid within-session preference for protein
Authors: Chiacchierini Giulia , Naneix Fabien , Apergis-Schoute John , McCutcheon James E
Published: January 2025

Evolution has provided species with adaptive behavioural mechanisms that guarantee tight dietary protein regulation. However, an unsolved question is whether the well-established preference for protein-containing food manifested during states of protein restriction is innate or learned. Here, we tackled this problem by maintaining male rats on either a low-protein diet (5% protein, protein-restricted) or a control diet (22% protein, non-restricted) for 9-12 days, and then offered them two novel foods, a protein-containing solution (4% casein) and a carbohydrate-containing solution (4% maltodextrin) during a daily 60-minute free-choice test, repeated for 5 consecutive days. We assessed both the total and cumulative intake of each solution throughout each test, as well as the microstructure of licking behaviour as an index of the solutions’ palatability. In a second experiment, we exposed a different cohort of rats, before any behavioural test, to the same protein source (i.e., casein) that they would encounter during the free-choice tests, to assess whether familiarity with casein would drive subsequent casein intake even in non-restricted rats. We found that dietary protein restriction leads to a rapid preference (within 16 minutes of first exposure) for a casein-rich solution, and this preference is persistent over subsequent exposures. Increased palatability of protein during initial exposure correlated with protein preference in the restricted rats. Moreover, familiarity with casein did not lead to protein preference in non-restricted rats. This study demonstrates that, when in need of protein, protein preference is a rapid adaptation that requires minimal experience of protein.

Highlights

Protein restricted rats rapidly show increased intake of a novel protein-containing solution.

Protein preference in protein-restricted rats is persistent across repeated exposures to protein-containing solution.

Changes in lick microstructure are associated with protein preference in protein-restricted rats.
Evaluation of porcine epidemic diarrhea virus RNA contamination on swine industry transportation vehicles
Authors: Parker Taylor B. , Meiklejohn Kelly A. , Machado Gustavo , Rahe Michael , Darrow Bradford Sean , Ferreira Juliana Bonin
Published: January 2025

Porcine epidemic diarrhea virus (PEDV) is one of the most devastating pathogens of global swine health and welfare. It is well known that contaminated fomites and vehicle movements play an important role in farm-to-farm PEDV spread, but the efficacy of cleaning and disinfection (C&D) protocols on the reduction in dissemination risk via vehicles and trailers remains unclear. This study used swine industry data to determine how frequently vehicles and trailers were contaminated with PEDV RNA before and after C&D. Environmental RNA samples were collected at three eastern North Carolina C&D sites from four different vehicle types: crew trucks, feed trucks, pigs-to-farm trucks and trailers, and pigs-to-market trucks and trailers. A total of 2,004 samples were collected from truck cabins, trailers, and tires before and after C&D with two commercial disinfectants at two different concentrations. An in-house RT-qPCR assay was used to detect the presence of PEDV RNA only (not infectivity status). Results suggest that pigs-to-market trucks hauling live pigs were the most likely to be contaminated with PEDV (82.06% of trucks tested positive before C&D and 89.55% tested positive after C&D), while feed trucks were the least likely contaminated (11.73% of trucks testing positive before C&D and 11.25% testing positive after C&D). Based on PEDV RNA detection, we demonstrated that quaternary ammonium and glutaraldehyde is a more effective disinfectant compared to advanced hydrogen peroxide in eliminating detectable PEDV RNA. Results also show that truck cabins are just as contaminated as the exterior of their vehicles. Based on these results, vehicle biosecurity measures should be evaluated and modified to prevent the spread of PEDV.
Knowledge of effort modulates visual memory biases for body postures
Authors: Han Qiu , Gandolfo Marco , van Dommelen Jules , Schoenmacker San , Drobnicki Klemens , Peelen Marius V.
Published: January 2025

The visual memory of others’ postures has been proposed to be shaped by knowledge and expectations. For example, the visual memory of a lifted arm was recently shown to be biased downward, suggesting that observers predicted the upcoming state of the arm based on knowledge of the effort required to hold the arm up against gravity. Alternatively, the downward bias for body postures could reflect an automatic normalization towards the most frequently observed arm position, with arms more often observed in a low position. Here, in three experiments, we provide evidence that the downward bias is flexibly modulated by knowledge of effort. In Experiment 1, we found a stronger downward bias for arm postures that are relatively effortful (lifting an arm above the shoulders while standing) compared to arm postures that are less effortful (lifting an arm above the chest while lying down). In Experiment 2, we found a stronger downward bias when the actor was standing (viewed from the side) than when the actor was lying down (viewed from above), even though the arm postures were visually identical. Moreover, dividing attention during the encoding stage reduced the bias, showing that attentive processing of the stimulus was required for the bias to emerge. Finally, in Experiment 3, we found that executing the observed posture during the visual memory task did not further increase the downward bias. Together, these findings demonstrate a high-level cognitive influence on the visual memory for body postures.
Single cell approaches define the murine leptomeninges:cortical brain interface as a distinct cellular neighborhood comprised of neural and nonneural cell types
Authors: Ebert Sarah N. , Eisner Christine , Karamboulas Konstantina , Bernier Louis-Philippe , Kaplan David R. , MacVicar Brian A. , Miller Freda D.
Published: January 2025

The interface between the brain surface and the adjacent meninges is a selective barrier regulating fluid, protein and immune cell exchange between the CNS and periphery. However, the cell types that form this important interface are not yet fully defined. To address this limitation, we have used single cell RNA-sequencing (scRNA-seq) and single cell spatial transcriptomics together with morphological lineage tracing and immunostaining to analyze the adult murine cortex. We show that the cortical interface is comprised of three major cell types, leptomeningeal cells, border astrocytes and tissue-resident macrophages. On the peripheral side the interface is comprised of transcriptionally-distinct PDGFRα-positive leptomeningeal mesenchymal cells that are intermingled with macrophages. This leptomeningeal pial layer is lined by a population of transcriptionally-distinct border astrocytes. The interface neighborhood is rich in growth factor mRNAs, including many leptomeningeal ligands predicted to act on both the border astrocytes and macrophages. On the CNS side of the interface is the relatively cell-sparse cortical layer one containing interneurons, microglia, parenchymal astrocytes, oligodendrocyte precursor cells and oligodendrocytes. Except for the border astrocytes, layer one cells are not closely-associated with the interface, suggesting that secreted ligands may be the major way the brain interface communicates with the underlying cortical parenchyma. Thus, our data provide a molecular/cellular resource describing the brain interface cell types and their interactions, thereby enabling future studies asking how this distinct cellular compartment regulates CNS:periphery interactions.

Significance Statement

Recent years have seen significant progress in identifying the diverse cell types within the meningeal space. However, the mechanisms by which these cells interact with glial and neuronal cells in layer one of the adult murine cortex remain poorly understood. During development, communication between radial precursors and meningeal layers is crucial for proper brain formation, but the role of this interaction in adulthood is still unclear. Additionally, how resident immune cells in the leptomeningeal space signal to layer one cortical cells or meningeal mesenchymal cells during homeostasis remains an open question. Understanding the identity, location, and interactions of these cells is essential for unraveling the complex dynamics at this critical brain interface.
Glo1 reduction in mice results in age- and sex-dependent metabolic dysfunction
Authors: Cely Ingrid , Blencowe Montgomery , Shu Le , Diamante Graciel , Ahn In Sook , Zhang Guanglin , LaGuardia Jonnby , Liu Ruoshui , Saleem Zara , Wang Susanna , Davis Richard , Lusis Aldons J. , Yang Xia
Published: January 2025

Objectives

Advanced glycation end products (AGEs) have been implicated as an important mediator of metabolic disorders including obesity, insulin resistance, and coronary artery disease. Glyoxalase 1 (Glo1) is a critical enzyme in the clearance of toxic dicarbonyl such as methylglyoxal, precursors of AGEs. The role of AGE-independent mechanisms that underly Glo1-induced metabolic disorders have yet to be elucidated.

Methods

We performed a longitudinal study of female and maleGlo1heterozygous knockdown (Glo1+/-) mice with ∼50% gene expression and screened metabolic phenotypes such as body weight, adiposity, glycemic control and plasma lipids. We also evaluated atherosclerotic burden, AGE levels, and gene expression profiles across cardiometabolic tissues (liver, adipose, muscle, kidney and aorta) to identify pathway perturbations and potential regulatory genes of Glo1 actions.

Results

Partial loss ofGlo1resulted in obesity, hyperglycemia, dyslipidemia, and alterations in lipid metabolism in metabolic tissues in an age- and sex-dependent manner.Glo1+/-females displayed altered glycemic control and increased plasma triglycerides, which aligned with significant perturbations in genes involved in adipogenesis, PPARg, insulin signaling, and fatty acid metabolism pathways in liver and adipose tissues. Conversely,Glo1+/-males developed increased skeletal muscle mass and visceral adipose depots along with changes in lipid metabolism pathways. For both cohorts, most phenotypes manifested after 14 weeks of age. Evaluation of methylglyoxal-derived AGEs demonstrated changes in only male skeletal muscle but not in female tissues, which cannot explain the broad metabolic changes observed inGlo1+/-mice. Transcriptional profiles suggest that altered glucose and lipid metabolism may be partially explained by alternative detoxification of methylglyoxal to metabolites such as pyruvate. Moreover, transcription factor (TF) analysis of the tissue-specific gene expression data identified TFs involved in cardiometabolic diseases such as Hnf4a (all tissues) and Arntl (aorta, liver, and kidney) which are female-biased regulators and whose targets are altered in response toGlo1+/-.

Conclusions

Our results indicate that Glo1 reduction perturbs metabolic health and metabolic pathways in a sex- and age-dependent manner without significant changes in AGEs across metabolic tissues. Rather, tissue-specific gene expression analysis suggests that key transcription factors such as Hfn4a and Arntl as well as metabolite changes from alternative methylglyoxal detoxification such as pyruvate, likely contribute to metabolic dysregulation inGlo1+/-mice.
Cell-free protein synthesis as a method to rapidly screen machine learning-directed protease variants
Authors: Thornton Ella Lucille , Boyle Jeremy T. , Laohakunakorn Nadanai , Regan Lynne
Published: January 2025

Machine learning (ML) tools have revolutionised protein structure prediction, engineering and design, but the best ML tool is only as good as the training data it learns from. To obtain high quality structural or functional data, protein purification is typically required, which is both time and resource consuming – especially at the scale required to train ML tools. Here, we showcase cell-free protein synthesis (CFPS) as a straightforward and fast tool for screening and scoring the activity of protein variants for ML workflows. We demonstrate the utility of the system by improving the kinetic qualities of a protease. By rapidly screening just 48 random variants to initially sample the fitness landscape, followed by 32 more targeted variants, we identified several protease variants with improved kinetic properties.
Distinct mechanisms for panoramic and landmark-based view integration in human scene-selective cortex
Authors: Han Linfeng Tony , Epstein Russell A.
Published: January 2025

To encode a cognitive map of an environment, a navigating agent must be able to integrate across disparate perceptual views corresponding to the same place. There are two ways that this can be done. First, the agent might integrate across the panorama of views obtainable at a single vantage point. Second, they might integrate across views of a distal location containing a landmark that is visible from multiple vantage points. Guided by previous work, we tested the hypothesis that these two viewpoint-integration processes would be mediated by different neuroanatomical substrates. Male and female human participants were familiarized with a route through a virtual city, along which they closely viewed 24 storefronts that were pairwise associated, either by being located on different buildings directly across the street from each other (same-panorama condition) or by being located on different sides of the same building facing different streets (same-landmark condition). They were then scanned with fMRI while viewing the storefronts in isolation and performing a spatial memory task. Multivoxel pattern analysis revealed a functional distinction between two scene-selective regions: the retrosplenial complex (RSC) showed a significant association effect for same-panorama storefronts, whereas the parahippocampal place area (PPA) showed a significant association effect for same-landmark storefronts. Panoramic association effects were also observed in several other dorsal-stream regions within the medial and lateral parietal lobe. These results demonstrate the existence of two neural mechanisms for integrating across views to represent places as either the observer’s location (same panorama) or the observed location (same landmark).

SIGNIFICANCE STATEMENT

An important component of spatial navigation is the ability to integrate across disparate views corresponding to the same place. Here we tested the idea that there are two such integration mechanisms in the human brain. Participants were familiarized with a virtual city and then scanned with fMRI while viewing storefronts from that city. Using multivariate pattern analysis, we find that the retrosplenial complex (RSC) and other parietal regions encode panoramas of views observed from specific locations, whereas the parahippocampal place area (PPA) encodes sets of views corresponding to specific landmarks. These results reveal two anatomically separated mechanisms for integrating views into places, thus advancing our understanding of how the brain forms cognitive maps of spatial environments.
Simultaneous Confidence Regions for Image Excursion Sets: a Validation Study with Applications in fMRI
Authors: Qin Jiyue , Davenport Samuel , Schwartzman Armin
Published: January 2025

Functional Magnetic Resonance Imaging (fMRI) is commonly used to localize brain regions activated during a task. Methods have been developed for constructing confidence regions of image excursion sets, allowing inference on brain regions exceeding non-zero activation thresholds. However, these methods have been limited to a single predefined threshold and brain volume data, overlooking more sensitive cortical surface analyses. We present an approach that constructs simultaneous confidence regions (SCRs) which are valid for all possible activation thresholds and are applicable to both volume and surface data. This approach is based on a recent method that constructs SCRs from simultaneous confidence bands (SCBs), obtained by using the bootstrap on 1D and 2D images. To extend this method to fMRI studies, we evaluate the validity of the bootstrap with fMRI data through extensive 2D simulations. Six bootstrap variants, including the nonparametric bootstrap and multiplier bootstrap are compared. The Rademacher multiplier bootstrap-t performs the best, achieving a coverage rate close to the nominal level with sample sizes as low as 20. We further validate our approach using realistic noise simulations obtained by resampling resting-state 3D fMRI data, a technique that has become the gold standard in the field. Moreover, our implementation handles data of any dimension and is equipped with interactive visualization tools designed for fMRI analysis. We apply our approach to task fMRI volume data and surface data from the Human Connectome Project, showcasing the method’s utility.
Operant House: A Versatile Open-Source Platform for Automated Operant Conditioning Testing of Mice in Home Cages
Authors: Otsuka Shintaro , Nakamura Yuriko , Ito-Ishida Aya , Suzuki Kunimichi , Ishikawa Ayako , Matsuda Keiko , Suyama Shigetomo , Contractor Anis , Yuzaki Michisuke
Published: January 2025

Operant conditioning is a valuable method for studying cognitive functions, yet its adoption is limited by low throughput, labor intensity, and high costs. Here, we developed “Operant House,” a low-cost, programmable device featuring a touchscreen, retractable levers, and a water reward port, designed for flexible, automated operant conditioning tasks. To validate its utility, we implemented two protocols to assess working memory in mice: a delayed non-match-to-position test and a two-choice spatial discrimination test. Using these protocols, we examined a mouse model of Alzheimer’s disease carrying familial Alzheimer’s disease-associated amyloid precursor protein mutations. Results revealed significant working memory deficits as early as 5 months of age. These findings highlight the Operant House as a cost-effective, high-throughput platform for evaluating higher cognitive functions in mice, offering an accessible tool for investigating models of neurological and neuropsychiatric disorders.
Odour representations supporting ethology-relevant categorisation and discrimination in the Drosophila mushroom body
Authors: Chan Ivy Chi Wai , Kalle Kossio Felipe Yaroslav , Tavosanis Gaia
Published: January 2025

Neural representations of sensory stimuli serve multiple distinct purposes, from the rapid recognition of familiar environments, to the precise identification of individual salient cues. In the insect mushroom body (MB), odours are encoded by the activity of Kenyon cells (KCs). The random wiring of olfactory projection neurons (PNs) and KCs in the MB calyx is thought to enhance odour discrimination. Here, we examined the impact of deviations from random wiring and demonstrated their significant roles in shaping odour representations. We confirm that different KC types have distinct PN input biases correlated with the contextual relevance of the odour information delivered by the PNs. By recording the functional responses of different KC types to ethologically defined odour categories, we found that the αβ and α'β' KCs produce segregated representations of relevant odour groups, potentially enhancing the categorisation of odours based on ethological relevance. Simultaneously, these same KC types displayed distinct representations for food-related odours, supporting precise discrimination. In contrast, γ KCs lacked significant segregation of odour representations by ethological category. Computational simulations refined with our functional data indicated that the specific PN input connection pattern of individual KC types largely accounts for the observed representations. Taken together, we propose that individual KC types process odour information with distinct objectives, supporting both ethological categorisation and discrimination.
Exploration of the Anticancer Activity ofSelaginella bryopterisderived silver nanoparticles
Authors: Dutta Ankita , Wadhwa Khushbu , Kumari Neha , Pandey Chetan , Kumar Anoop , Kapoor Neha
Published: January 2025

Abstract

Ovarian cancer is characterized by chronic hormonal imbalances and associated symptoms like irregular menstruation, fertility problems and abdominal discomfort. Poly ADP-ribose polymerases (PARPs) are proteins that play a crucial role in DNA repair pathways like base excision repair (BER). PARP family proteins exhibit catalytic activities which facilitate the transport of ADP-ribose to targeted proteins. Inhibition of PARP proteins in cancer cells withBRAC1/2gene mutations impairs the process of Single Strand Break (SSBs) repairs followed by Double Strand Breaks (DSBs), stalling replication, leading to apoptosis. PARP1 protein inhibition is an innovative therapeutic approach in cancer treatment. Commercially available drugs like Olaparib and Rucaparib are used as PARP1 inhibitors to treat ovarian cancer, however the development of effective new therapeutic drugs is urgently needed to overcome drug toxicity and resistance. In this study, we synthesized silver nanoparticles (AgNPs) from the leaf extract ofSelaginella bryopterisdemonstrating their cytotoxic nature against the ovarian cancer SKOV-3 cell line, with an IC50value of 7.81µg/ml. We also observed cell death in cancer cells with an ROS upsurge induced byS. bryopterisAgNPs. Our findings also elaborate on the role of Rhamnetin, aS. bryopterisphytochemical that exhibits active site targeting of PARP-1 residues.
A mosaic gastruloid model highlights the developmental stage-specific restriction of cell competition in mammalian pre-gastrulation
Authors: Frenster J.D. , Babin S. , Josende Garcia J.B. , Casani Galdon P. , Pascual-Mas P. , Robertson G. , Garcia Ojalvo J. , Martinez Arias A.
Published: January 2025

In early mammalian embryogenesis, the selective elimination of suboptimal cells is critical for developmental integrity. Cell competition (CC) is a cell non-autonomous quality control in which “winner” cells eliminate viable but suboptimal “loser” cells based on their relative difference in fitness. Due to its central role in fitness perception, loss of p53 results in the emergence of “supercompetitor” cells, which stand at the apex of cell competition and induce apoptosis in neighboring wild-type (WT) cells.

Here, we investigate CC dynamics using mosaic 3D mouse gastruloids, an embryonic stem cell (ESC)-basedin vitromodel of gastrulation, composed of defined numbers of WT and p53-KO cells. In mosaic gastruloids, even low numbers of p53-KO cells robustly outcompete WT cells, and introduction of as few as two p53-KO cells is sufficient to measurably impair neighboring WT cell growth. CC in gastruloids is independent of cell proliferation rates, nutrient availability, or reactive oxygen species (ROS), and not influenced by Nodal and ERK signaling. However, we observe that Wnt and BMP signaling protect from CC, which is exclusively driven by intrinsic apoptosis, as indicated by Bcl2-mediated complete rescue of WT cells. During gastruloid development, CC is temporally restricted to a window of 48–96 hours after aggregation, mirroring embryonic days E5.5–E7.5 in the mouse. Heterochronic mosaic gastruloid experiments demonstrate that relative differences in pluripotency levels are neither necessary nor sufficient to cause supercompetition, but that CC is contingent on both competitors residing within the developmental window permissive to CC. Neither pluripotent mosaic 3D aggregates, nor 3D EpiGastruloids, which model more advanced developmental processes, display any competition, supporting the hypothesis that developmental CC is specific to the onset of gastrulation. Our findings offer insights into the mechanisms of cell fitness evaluation in mammalian embryogenesis and establish gastruloids as a powerful 3D model for investigating developmental stage-specific cell competition.
Contributions of distinct attention mechanisms to saccadic choices in a gamified, dynamic environment
Authors: Kattner Evan A , Stanford Terrence R , Salinas Emilio
Published: January 2025

Visuospatial attention is key for parsing visual information and selecting targets to look at. In turn, three types of mechanism determine when and where attention is deployed: stimulus-driven (exogenous), goal-driven (endogenous), and history-driven (reflecting recent experience). It is unclear, however, how these distinct attentional signals interact and contribute during natural visual scanning, when stimuli may change rapidly and no fixation requirements are imposed. Here, we investigate this via a gamified task in which participants make continuous saccadic choices at a rapid pace --- and yet, perceptual performance can be accurately tracked over time as the choice process unfolds. The results reveal unequivocal markers of exogenous capture toward salient stimuli; endogenous guidance toward valuable targets and relevant locations; and history-driven effects, which produce large, involuntary modulations in processing capacity. Under dynamic conditions, success probability is dictated by temporally precise interplay between different forms of spatial attention, with recent history making a particularly prominent contribution.
BubR1 and Mad2 regulate adult midgut remodeling inDrosophiladiapause
Authors: Adachi Yuya , Nagai Hiroki , Fujichika Takako , Takahashi Aya , Miura Masayuki , Nakajima Yu-ichiro
Published: January 2025

Diapause is a survival strategy in which growth and aging are temporarily suspended, enabling animals to withstand unfavorable environments. Various insects, including the fruit flyDrosophila, enter reproductive diapause, or dormancy, in response to colder temperatures and/or shorter day lengths. During reproductive diapause, ovarian development halts, and non-reproductive organs also undergo remodeling at both morphological and metabolic levels: however, the mechanisms underlying this remodeling and its physiological impact remain largely unclear. Here, we show that theDrosophilaadult midgut undergoes extensive remodeling in diapause, marked by a sustained suspension of growth due to the cell cycle arrest of intestinal stem cells (ISCs) that revert to normal upon returning to recovery conditions. During dormancy, BubR1 and Mad2, key regulators of mitosis, are highly expressed and localized in the cytoplasm of ISCs rather than at the kinetochore, and both BubR1 and Mad2 are essential for diapause-specific midgut remodeling. Furthermore, disruption of midgut growth arrest during diapause reduces the resistance to starvation in adult flies. Together, our findings identify a novel role for BubR1 and Mad2 in ISCs–promoting proper midgut remodeling during dormancy–and highlight the importance of this process for survival under adverse environments.
Applicability of lean techniques and processes on improving sustainability in construction projects
Authors: Gupta Prachee , Elhag Taha
Published: January 2025

Purpose

The construction industry is known for its complexity, poor performance and impact on the environment. This study investigates the applicability of lean techniques and processes on improving sustainability in construction projects. A total of ten key lean construction (LC) tools are analyzed for impact on 15 sustainability categories and 78 subcategories. Results are summarized for usability across the three sustainability pillars.

Design/methodology/approach

A systematic literature review (SLR) of articles published over the last 10 years (2014–2023) on lean and sustainable construction is conducted involving planning, identifying, screening, analyzing and reporting phases. Selected 41 articles are reviewed in detail. For reporting, the applicability of LC tools is critically analyzed and ranked according to impact on sustainability over two project stages.

Findings

Literature suggests that the impact of LC on economic waste reduction or social impact is likely to have an impact on environmental sustainability as well. Overall, the top LC tools for improving sustainability in construction include value stream mapping (VSM), just-in-time (JIT) and 5S. The applicability of the LC tools is more prevalent in the “construction phase” of construction projects than the “planning and design” phase.

Originality/value

This study analyzed ten lean tools through SLR and evaluated their impact on construction sustainability. By assessing the challenges and benefits associated with LC tools, the outcomes of the study support the adoption of LC by stakeholders. The paper also proposed a practical implementation strategy for LC tools to enhance sustainable construction.
The visible-invisible tension of slum tourism influencers
Authors: Fernandes Adalberto
Published: January 2025

Purpose

This paper aims to investigate the tension between the visible and invisible aspects in slum tourism influencers’ content, addressing a gap in the literature regarding this kind of influencers and enhancing visual methodologies by including the analysis of invisible phenomena.

Design/methodology/approach

This paper is a qualitative analysis of the most-watched slum tourism influencers’ content in Brazilian ‘favelas’ (totaling 24,000,000 views) using Rancière's (2004) visual research framework and interpretation of the most frequent words in 27,000 comments on these videos.

Findings

Slum tourism influencers often attempt to depict what cannot be shown due to risks to the hosts and influencers. The inability to show certain aspects is compensated by the proliferation of alternative images hinting at the unseen. Comments reveal that while the desire to perceive the unseen may drive viewership, the influencers and locals emerge as the primary visual focal points. Consequently, the marginalized setting of the slum fades into the background, with individuals taking precedence in viewers’ discussions.

Originality/value

To the best of the author’s knowledge, this study is the first to explore the role of the invisible in slum tourism influencer content and followers’ reactions. It illustrates that rather than imposing restrictions on the visible, the invisible serves as a catalyst for the proliferation of images through alternative means.
Compliant assembly of complex aviation plugs combining multi-agent search and variable parameters
Authors: Liu Zhenghai , Tang Hui , Liu Dong , Zhao Jingji , Zhu Xinyue , Du Yu , Tian Xiaojing , Cong Ming
Published: January 2025

Purpose

In response to the complex external structure of high-precision aviation plugs, which makes it difficult to search outside the hole and adjust inside the hole during automated assembly. This paper aims to propose an assembly framework that combines multi-agent search and variable parameter compliant control to solve this problem.

Design/methodology/approach

First, a multi-agent search strategy (MAS) based on Gaussian Mixture Model and Deep Q-Network was proposed to optimize displacement direction and actions, thereby improving search speed and success rate. Then, a variable parameter admittance control method (RL-VPA) based on dual delay depth deterministic policy gradient (TD3) was proposed, which dynamically optimized the internal parameters of the admittance controller and adopted state space discretization to improve convergence speed and assembly efficiency.

Findings

Compared to spiral search and single-agent search, the average search success rate has improved by approximately 10% and 6.6%. Compared to fixed admittance control and other RL-based methods, the average assembly success rate has increased by approximately 38.6%, 22% and 8.6%. Compared with the training results of the model without state discretization, it was found that state discretization helps the model converge quickly. To verify the generalization ability of the assembly framework, experiments were conducted on three different pin counts of aviation plugs, the assembly success rate reached 86.7%, all of which showed good assembly results. Finally, combining state space discretization to reduce the impact of environmental noise, improve training effectiveness and convergence speed.

Originality/value

MAS has been proposed to optimize displacement direction and action, improving search speed and success rate. RL-VPA is designed to dynamically optimize the internal parameters of the admittance controller, enhancing the robustness and generalization ability of the model. Additionally, state space discretization is combined to improve training effectiveness and convergence speed.
Interaction in a time of crisis: buyer-supplier adaptation in public healthcare
Authors: Abrahamsen Morten H. , Munksgaard Kristin B.
Published: January 2025

Purpose

This paper aims to examine adaptation in buyer–seller relationships in a time of crisis and to explore what consequences adaptation has for the actors involved. The authors are particularly interested in examining how suppliers and public buyers adapt in turbulent situations where public policy opens for interaction in a mode represented by studies in the industrial marketing and purchasing research approach. The COVID-19 pandemic represents such a unique research setting, as it opens up insights into how buyers and suppliers had to adapt in a matter of days in response to rapid and turbulent changes in their business environment. In this paper, the authors seek insights into the following research questions: What role do the actors’ interpretation of the situation play in the adaptation process? How do adaptation processes unfold in a time of national crisis? What are the actor and relationship-specific outcomes from adaptation in such a situation?

Design/methodology/approach

To answer these questions, the authors present data from an exploratory case study of intra- and interfirm adaptation processes between public buyers and private suppliers in the health-care sector during the COVID-19 pandemic. The pandemic opened for access to a unique data from personal interviews and secondary data, from public reports and newspaper/media coverage at intervals during the outbreak and at the aftermath of the pandemic.

Findings

The authors find that the actors’ interpretation of the situation and their motivation to engage in adaptations play an important role in the adaptation processes. In particular, a normative commitment based on a moral duty to contribute to dealing with the turbulent situation of society is found to be a main driver. In these situations, shared sensemaking and alignment of mental models help to mobilise actors, resources and activities into new interaction patterns. At the same time, mutual affective commitment between the buyer and suppliers is not significant over time, thus constraining and eventually terminating the adaptation processes.

Originality/value

This study contributes to the understanding of interaction between public buyers and suppliers during turbulent situations. Changes in the adaptation context opens for extensive interaction, thus enabling actors to combine and exploit resources of value, but temporary adaptations do not create long-term effects on the ability to develop buyer–supplier interaction in public markets.
Gendered AI in fully autonomous vehicles: the role of social presence and competence in building trust
Authors: Pavone Giulia , Desveaud Kathleen
Published: January 2025

Purpose

This study aims to examine users’ perceptions of gendered artificial intelligence (AI) interfaces in the context of autonomous vehicles (AVs). It focuses on the gendered effects of social presence, warmth and competence on trust and introduces the moderating role of perceived autonomy as a key factor.

Design/methodology/approach

A between-subjects experimental design was used (n = 309), using a 360-degree virtual tour simulation with gendered voice assistants.

Findings

As AVs are perceived as highly autonomous, the impact of gender on social presence intensifies, affecting trust. Female voices enhance social presence, conveying warmth but also perceived competence traits. Notably, competence impacts trust more significantly than warmth.

Research limitations/implications

The study’s experimental approach might not fully capture real-world interactions with AVs. Future research could benefit from field and longitudinal studies.

Practical implications

These findings are crucial for AV designers and interface developers. They highlight the importance of considering human-like characteristics such as gender and enhance perceptions of competence in developing highly autonomous AI interfaces.

Social implications

Addressing gender stereotypes in AV design is vital to ensure inclusivity, to cater for a diverse user base and to give all users a trustworthy experience.

Originality/value

This study is pioneering in its examination of how gender stereotypes impact trust toward AVs, an area previously unexplored, despite the significant influence gender might have due to the high level of autonomy and traditional car-related stereotypes. It uniquely identifies feminine traits as denoting competence in highly autonomous technologies like AVs, especially where safety is critical. This challenges traditional gender stereotypes and emphasizes the need to rethink attributes associated with competence and trust in AI.
Machinability optimization of carbon fiber reinforced polymer composites for aviation manufacturing parts
Authors: Şirin Aysun , Aytaç Ayhan , Şeker Ulvi
Published: January 2025

Purpose

Surface roughness and delamination during the milling of carbon fiber reinforced polymer (CFRP) composite parts in aviation can lead to component rejection. This article aims to optimize cutting conditions to reduce these failures while ensuring compliance with aviation standards. By improving machinability, the goal is to minimize part rejection rates and scrap, optimizing costs and increasing safety.

Design/methodology/approach

Full factorial experimental design and response surface methodology (RSM) were used to establish relationships between the cutting parameters and the cutting force, delamination and surface roughness. To validate the model and identify significant parameters, analysis of variance (ANOVA) was performed. The cutting parameters were optimized to reduce cutting force and improve surface quality using ANOVA and RSM.

Findings

The lowest response values can be achieved with a cutting speed of 285.35 m/min and a feed of 358.57 mm/min using the Aluminum Chromium Nitride (AlCrN)-coated tool. Accordingly, the optimum cutting force was obtained as 190.97 N, delamination depth as 1.562 mm and surface roughness as 1.431 µm. It has been seen that the obtained surface roughness and delamination values are consistent with aviation literature studies, sectoral data and standards.

Originality/value

This study uniquely examines cutting force, surface roughness and delamination using Titanium Aluminum Nitride (TiAlN)- and AlCrN-coated tools instead of traditional Poly Cyristaline Diamond (PCD) tools. It employs a two-stage experimental framework, starting with a full factorial design followed by RSM. The initial data have been used as inputs for optimization in the second stage to achieve more accurate results.