bluuebunny/crossref_metadata_2025_split huggingface dataset:
LubriShieldTM- a unique permanent coating for indwelling urinary catheters that impedes surface-associated uropathogens from forming biofilm
Authors: Romero Ana I. , Surkov Serhiy , Wirsén Per , Brookes Graeme , Bergström Linda , Tejbrant Jan , Dhamo Elena , Wilks Sandra , Bryant Catherine , Andersson Jan 
Published: January 2025

AbstractCatheter-associated urinary tract infection (CAUTI) is one of the most common healthcare-associated infections and biofilm formation plays a key role in its pathogenesis. Indwelling medical devices introduce ideal pathways inside the body for invading pathogens and feature surfaces conducive to biofilm development. These devices are the root cause of severe clinical infections often recalcitrant to antimicrobials. When bacteria and fungi switch to biofilm mode of growth, they produce a matrix in the form of extracellular polymeric substances (EPS). This creates a unique environment for growing virulent colonizers and persisting cells while also forming a shielding barrier against immune system attacks, antimicrobial agents and mechanical removal by fluid shear forces.To address this challenge, LubriShieldTM- a novel permanent coating was invented, and evenly applied to both the internal and external surfaces of indwelling urinary Foley catheters. Without releasing active substances, it effectively prevented pathogens from producing biofilm. The coating was superhydrophilic and incorporated a proprietary anti-fouling ligand, which created a surface that significantly inhibited up to 99% of colonizing uropathogens from forming biofilm for the duration of use without any microbial killing (p< 0.001). The predominant uropathogens, including Gram-positive and Gram-negative as well as Candida albicans, were inhibited from forming biofilm on the LubriShieldTMcoated surfaces for up to 14 days in artificial urine medium. After challenging the adhering bacteria in a glass bladder flow model, the coating still significantly reduced biofilm formation by 83% (p<0.001).The growth mode and emergent properties of adhering bacteria on uncoated silicone catheter surfaces were compared with those on LubriShieldTMcoated surfaces. RNA-seq analysis revealed that gene expression associated with microbial EPS formation was significantly downregulated on the coated surfaces. Additionally, microorganisms adhering to LubriShieldTMcoated catheters were 46% more susceptible to antibiotics compared to those on uncoated silicone catheters (p<0.01).
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

ABSTRACTWhile 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.SignificanceAstrocytes 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

ABSTRACTUnderstanding 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 SummaryThis 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.HighlightsContinuous 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

BackgroundIn 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.MethodsWe 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.ResultsKey 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).ConclusionsThis 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

AbstractEvolution 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.HighlightsProtein 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

AbstractPorcine 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

AbstractThe 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

AbstractThe 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 StatementRecent 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

ABSTRACTObjectivesAdvanced 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.MethodsWe 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.ResultsPartial 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+/-.ConclusionsOur 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

AbstractMachine 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.