bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder
Authors: Zadka Łukasz , Eggerstorfer Benjamin , Buzalewicz Igor , Vraka Chrysoula , Rusak Agnieszka , Godbersen Godber M , Opalińska Agnieszka , Unterholzner Jakob , Ulatowska-Jarża Agnieszka , Philippe Cecile , Haczkiewicz-Leśniak Katarzyna , Silberbauer Leo R , Murgaš Matej , Nics Lukas , Hahn Andreas , Hacker Marcus , Gomułkiewicz Agnieszka , Rujescu Dan , Podhorska-Okołów Marzenna , Lanzenberger Rupert , Gryglewski Gregor 
Published: February 2025

AbstractWith their ability to cross the blood-brain barrier, transport and regulate the release of various signaling molecules, extracellular vesicles (EVs) constitute a novel avenue to study intercellular communication in various pathologies, including psychiatric disorders. We studied 34 major depressive disorder (MDD) patients and 57 healthy controls and characterized EVs isolated from plasma using digital holographic tomography (DHT) and nanoparticle tracking analysis (NTA). EVs detected in DHT were markedly smaller and less variable in size in MDD patients. Furthermore, a lower variance of refractive indices related to the dry mass density of EVs was observed in patients. Meanwhile, NTA revealed a trend for elevated concentration of EVs in MDD. In DHT, EV dimensions correlated with plasma mRNA expression of exosomal markersCD63andCD9, with corresponding alterations in MDD. Levels of EV concentration andCD9were both negatively correlated with antidepressant treatment response. Utilizing electron microscopy and immunoblots we confirmed the presence of serotonin transporters (SERT) as EV cargo. SERT levels in EVs correlated with cerebral SERT binding potential in the amygdala measured using positron emission tomography. Next to the implication of altered EV communication in mood disorders, the pronounced differences in plasma EV characteristics and exosomal markers in MDD might inform the development of assays with diagnostic or prognostic value for clinical practice.
Vibrio harveyiplasmids as drivers of virulence in barramundi (Lates calcarifer)?
Authors: Sullivan Roisin , Becker Joy A , Zadoks Ruth N , Venturini Carola , Esteves Ana I. S. , Benedict Suresh , Fornarino Dani L , Andrews Hannah , Okoh God’spower R , Bhardwaj Vidya , Sistrom Mark , Westman Mark E , Phuoc Nguyen Ngoc , Samsing Francisca 
Published: February 2025

AbstractVibriospecies are an emerging public and animal health risk in marine environments and the opportunistic bacterial pathogenVibrio harveyiis a major disease risk for tropical aquaculture. Current understanding of virulence inV. harveyiis limited by strain-specific variability and complex host-pathogen dynamics. This study sought to integrate genomic investigation, phenotypic characterisation andin vivochallenge trials in barramundi (Lates calcarifer)to increase our understanding ofV. harveyivirulence. We identified two hypervirulent isolates, Vh-14 and Vh-15 that caused 100% mortality in fish within 48 hours, and that were phenotypically and genotypically distinct from otherV. harveyiisolates. Virulent isolates contained multiple plasmids, including a 105,412 bp conjugative plasmid with type III secretion system genes originally identified inYersinia pestis. The emergence of this hypervirulent plasmid-mediated patho-variant poses a potential threat to the sustainable production of marine finfish in Southeast Asia, the Mediterranean and Australia. In addition, we observed an effect of temperature on phenotypic indicators of virulence with an increase in activity at 28°C and 34°C compared to 22°C. This suggests that temperature fluctuations associated with climate change may act as a stressor on bacteria, increasing virulence gene secretion and host adaptation. Our results utilising a myriad of technologies and tools, highlights the importance of a holistic view to virulence characterisation.
Dynamic context-based updating of object representations in visual cortex
Authors: Aldegheri Giacomo , Gayet Surya , Peelen Marius V. 
Published: February 2025

AbstractIn everyday vision, objects in scenes are often poorly or only partially visible, for example because they are occluded or appear in the periphery. Previous studies have shown that the visual system can reconstruct missing object information based on the spatial context in static displays. Real-world vision is dynamic, however, causing the visual appearance of objects (e.g., their size and viewpoint) to change as we move. Importantly, these changes are highly predictable from the 3D structure of the surrounding scene, raising the possibility that the visual cortex dynamically updates object representations using this predictive contextual information. Here, we tested this hypothesis in two fMRI studies (N=65). Experiment 1 showed that visual representations of objects were sharpened when they rotated congruently (rather than incongruently) with the surrounding scene. Moreover, Experiment 2 showed that the updated orientation of the object (as dictated by the surrounding scene) could be decoded from visual cortex activity, even when the object itself was not visible. These findings indicate that predictive processes in the visual cortex follow the geometric structure of the environment, thus providing a mechanism that leverages predictions to aid object perception in dynamic real-world environments.
EFFECT OF OMEGA 3 SUPPLEMENTATION DURING PREGNANCY AND LACTATION ON COGNITIVE FUNCTIONS IN RAT OFFSPRING
Authors: Onur Öztürk Hande Nur , Türker Perim Fatma 
Published: February 2025

AbstractAimThis study investigates the effects of omega-3 supplementation starting in the preconception period, during the 1st, 2nd, and 3rd weeks of pregnancy, and lactation on the cognitive functions of rat offspring.MethodsThe study involved 30 mother rats divided into a test group receiving 400 mg/kg/day omega-3 supplementation via oral gavage and a control group with no supplementation. Omega-3 supplementation began at different stages for each group and continued through the lactation period (21 days). Two male pups from each mother, for a total of 60 pups, were tested for cognitive function at 45 days using the Morris Water Maze to assess spatial learning and reference memory.ResultsSignificant differences were found between groups in initial weights, pre-mating weights, pre-birth weights, number of pups, and gestation duration (p<0.05), but not in weight gain during pregnancy (p>0.05). The time to find the platform on test days 1 and 2 was significantly different between groups (p<0.05). Differences in platform-finding times across trials were also significant (p<0.05). However, no significant difference was found in the probe test on day 5 (p>0.05).ConclusionInitiating omega-3 supplementation during the early stages of pregnancy may be more effective for both short-term and long-term memory.
The role of human intraparietal sulcus in evidence accumulation revealed by EEG and model-informed fMRI
Authors: Wongtrakun Jaeger , Zhou Shou-Han , O’Connell Redmond G. , Chong Trevor T.-J. , Bellgrove Mark A. , Coxon James P. 
Published: February 2025

AbstractSequential sampling models propose that the repeated sampling of sensory information is a fundamental component of perceptual decision-making. Electroencephalographic investigations in humans have demonstrated motor-independent representations of evidence accumulation, but such observations have seldom been made in neuroimaging studies exploring the neuroanatomical origins of evidence accumulation. Here, we aimed to reveal the neuroanatomical locus of sensory evidence accumulation in the human brain by regressing an electrophysiological marker of evidence accumulation (centroparietal positivity, CPP) against changes in blood oxygen level-dependent (BOLD) signal during perceptual decision-making. Our cross-modal imaging approach revealed a cluster within left intraparietal sulcus (IPS), located within putative lateral intraparietal area (region hIP3), for which BOLD signals scaled in relation to the slope of the CPP. Furthermore, the drift rate parameter of a drift diffusion model parametrically modulated BOLD activity within an overlapping region of left IPS. In contrast, parametric modulation by reaction time revealed a distributed fronto-parietal network, demonstrating the utility of our approach for isolating a discrete neuroanatomical locus of evidence accumulation. Together, our findings provide strong support for intraparietal sulcus involvement in the accumulation of sensory evidence during human perceptual decision-making.
The role of toxin/antidote genes in the maintenance and evolution of accessory chromosomes inFusarium
Authors: Sandell Linnea , Forsythe Adrian , Mirandola Anna , Jorayev Samuel , Urquhart Andrew , Farbos Alexandra Granger , Saupe Sven J. , Vogan Aaron A. 
Published: February 2025

AbstractThe genomic diversity of many fungal species is augmented by accessory chromosomes, which are variably present in individual strains. These genomic regions evolve rapidly, accumulating genes important in pathogenicity but also harboring significant amounts of transposable elements (TEs). This duality suggests a trade-off: accessory chromosomes provide infection-related benefits while otherwise being deleterious due to their highly repetitive nature and contributions to genomic instability. Despite this, accessory chromosomes often appear to be stably maintained even when strains are grown on media, with no plant host. Previously, we had observed that genes homologous to meiotic drive toxin/antidote proteins fromPodospora anserina(Spoks) are abundant on accessory chromosomes in variousFusariumspecies. Using a functionality screen in yeast, we demonstrate that some of these homologs have active toxin and antidote properties. We propose that these selfish genes act to maintain accessory chromosomes during vegetative growth and may influence their spread via parasexual cycles. Finally, asSpokgenes are mobilized by the newly described TE superfamilyStarships, it suggests these TEs play crucial roles in forming accessory chromosomes and regions. These results illuminate a mysterious facet of fungal biology, a key step towards describing the origin, spread, and maintenance of pathogenicity in many fungal species.
BMAL1Overexpression in Suprachiasmatic Nucleus Protects from Retinal Neurovascular Deficits in Diabetes
Authors: Mahajan Neha , Luo Qianyi , Lukkes Jodi , Abhyankar Surabhi D , Bhatwadekar Ashay D 
Published: February 2025

AbstractThe suprachiasmatic nucleus (SCN) regulates circadian rhythms and influences physiological and behavioral processes. Disruptions in circadian rhythms (CRD) are observed in type 2 diabetes (T2D), and importantly, CRD acts as an independent risk factor for T2D and its associated complications. BMAL1, a circadian clock gene, is vital for sustaining an optimal circadian rhythm and physiological function. However, the therapeutic potential of BMAL1 overexpression in the SCN to rectify the neurovascular deficits of T2D has yet to be investigated. In this study, db/db mice, a well-established model of T2D exhibiting arrhythmic behavior and the complications of diabetes, were injected stereotaxically with AAV8-Bmal1 or a control virus in the SCN to evaluate the protective effects of correcting the central clock on neurovascular deficits. Given the complex neurovascular network and the eye’s unique accessibility as a transparent system, ocular complications were selected as a model to examine the neuronal functional, behavioral, and vascular benefits of correcting the central clock. BMAL1 overexpression normalized the circadian rhythms, as demonstrated by improvements in the free-running period. The retinal neuronal function improved on electroretinogram, along with optomotor behavior and visual acuity enhancements. Retinal vascular deficits were also significantly reduced. Notably, our approach helped decrease fat content in genetically predisposed obese animals. Since the SCN is known to regulate hepatic glucose production via sympathetic mechanisms, glycemic control, and pyruvate tolerance tests were conducted. Systemically, we observed improved glucose homeostasis in BMAL1-overexpressing mice alongside a substantial reduction in hepatic gluconeogenesis. BMAL1 overexpression lowered plasma norepinephrine and liver TH levels, indicating a protective regulation of adrenergic signaling. Thus, this study underscores the therapeutic potential of targeting circadian clock genes like BMAL1 in the SCN to alleviate metabolic and neurovascular deficits associated with T2D. Our research offers a compelling framework for integrating circadian rhythms into managing diabetes and its complications.
Disrupted spatial and contextual memory encoding in the hippocampus of 5xFAD mice precedes cognitive impairment
Authors: Li Yimei , Go Mary Ann , Zhang Hualong , Schultz Simon R 
Published: February 2025

AbstractAlzheimer’s disease (AD) is marked by progressive cognitive decline, yet the underlying neural mechanisms are not fully understood. To address this, we investigated hippocampal activity in 5xFAD model mice performing a continuous spatial alternation task, combining behavioural assessment within vivotwo-photon calcium imaging. Young 5xFAD mice exhibited mild performance deficits, which worsened with age. Older 5xFAD mice showed significant impairments in task acquisition and alternation accuracy, with significant behavioural hyperactivity. Hippocampal CA1 neurons in 5xFAD mice showed early impairments in spatial representation, prior to showing behavioural deficits. Both young and old 5xFAD mice exhibited reduced spatial tuning, fewer place cells, and decreased trial-to-trial reliability in comparison to wildtype sibling controls. Additionally, 5xFAD mice demonstrated disrupted spatial encoding of reward locations, with reduced spatial correlation between correct and error trials. Analysis of hippocampal “splitter” cells revealed reduced splitting activity in 5xFAD mice, with reduced discriminability and reliability of trajectory-dependent activity. These deficits correlated with poorer task performance, suggesting that disrupted contextual encoding contributes to cognitive decline in AD. Our findings highlight early disruptions in hippocampal spatial and contextual encoding in 5xFAD mice, which precede behavioural impairments and provide insights into AD pathophysiology.TeaserTwo-photon imaging in behaving AD mice reveals impairments in spatial and contextual memory circuits prior to cognitive deficits.
Evolutionary trends inBombellaapis CRISPR-Cas systems
Authors: Ganote Carrie L , Caesar Lílian , Rice Danny W , Whitaker Rachel J , Newton Irene LG 
Published: February 2025

ABSTRACTBacteria and archaea employ a rudimentary immune system, CRISPR-Cas, to protect against foreign genetic elements such as bacteriophage. CRISPR-Cas systems are found in Bombella apis, a microbe associated with honey bee queens, brood, and royal jelly. Unlike other honey bee microbiome members, B. apis does not colonize the worker bee midgut or hindgut and has therefore been understudied with regards to its importance in the honey bee colony. However, B. apis appears to play beneficial roles in the colony, by protecting developing brood from fungal pathogens and by bolstering their development under nutritional stress. Previously we identified CRISPR-Cas systems as being acquired by B. apis in its transition to bee association, as they are absent in a sister clade. Here we assess the variation and distribution of CRISPR-Cas types across B. apis strains. We found multiple CRISPR-Cas types, some of which have multiple arrays, within the same B. apis genomes and also in the honey bee queen gut metagenomes. We analyzed the spacers between strains to identify the history of mobile element interaction for each B. apis strain. Finally, we predict interactions between viral sequences and CRISPR systems from different honey bee microbiome members. Our analyses show that the B. apis CRISPR-Cas systems are dynamic, that microbes in the same niche have unique spacers which supports the functionality of these CRISPR-Cas systems, and that acquisition of new spacers may be occurring in multiple locations in the genome, allowing for a flexible antiviral arsenal for the microbe.IMPORTANCEHoney bee worker gut microbes have been implicated in everything from protection from pathogens to breakdown of complex polysaccharides in the diet. However, there are multiple niches within a honey bee colony that host a different group of microbes, including the acetic acid bacteriumBombella apis. B. apisis found in the colony food stores, in association with brood, in worker hypopharyngeal glands, and in the queen digestive tract. The roles thatB. apismay serve in these environments are just beginning to be discovered and include production of a potent antifungal that protects developing bees and supplementation of dietary lysine to young larvae, bol-stering their nutrition. Niche specificity inB. apismay be affected by the pressures of bacteriophage and other mobile elements which may target different strains in each specific bee environment. Studying the interplay betweenB. apisand its mobile genetic elements (MGEs) may help us better understand microbial community dynamics within the colony and the potential ramifications for the honey bee host.
The impact of perturbation intensity schedule on improvements in reactive balance control in young adults: an experimental study
Authors: Wong Piufat , Yeh Isabel , Mansfield Avril , McCrum Christopher 
Published: February 2025

ABSTRACTBackgroundReactive balance training (RBT) uses unanticipated perturbations to improve balance reactions and prevent falls. Intensity and predictability of perturbations may affect the generalizability of RBT, but their relative contributions remain unclear. This study aimed to compare the effects of three RBT schedules with differing intensity and predictability on participants’ balance recovery following untrained perturbations, and to determine perceived difficulty and challenge of the training schedules.MethodsParticipants were 36 healthy young adults (20-35 years). Participants were randomly assigned to one of three RBT intensity schedules (fixed high intensity, low-to-high intensity, and variable intensity). Training took place on a motion platform that delivered perturbations in varying directions (forward, backward, left, and right) and intensities across five trial blocks. Balance reactions (number of recovery steps) pre- and post-training, and electrodermal responses, and perceived difficulty during training were collected. Statistical analyses compared post-training outcomes between training groups, controlling for the baseline value.ResultsParticipants took fewer steps and decreased the proportion of multi-step reactions pre- to post-training (p<0.0001), with no significant between-group differences. Perceived exertion decreased significantly across training blocks in the fixed-high group and increased significantly in the low-to-high group. Electrodermal responses declined across all groups between training blocks 1 and 3 (p=0.017).ConclusionsImprovements in step reactions to untrained perturbations did not differ between training groups, highlighting the importance of multi-directional variability over specific intensity schedules for enhancing balance recovery.
Dietary quorum quenching AHL lactonase impairs the adaptation of commensal bacterium to host innate immunity
Authors: Xia Rui , Yao Yuanyuan , Meng Delong , Zhao Yajie , Xu Shichang , Jin Ya , Zhang Zhen , Yang Yalin , Ran Chao , Zhou Zhigang 
Published: February 2025

AbstractQuorum sensing (QS) is the communication system of bacteria that depends on QS signals. Quorum quenching (QQ) enzymes degrade QS signals and are promising alternatives of antibiotics to treat bacterial infections. Here, we found that dietary QQN-acyl homoserine (AHL) lactonase led to microbiota dysbiosis in zebrafish, with reduction ofAeromonasand enrichment ofPlesiomonas. Through gnotobiotic zebrafish colonized with a minimal microbiota, we found that QQ-mediated microbial alteration relies on host Myd88 signaling and neutrophil elastase. Mechanistically, quorum quenching increased the susceptibility of commensalAeromonasto host neutrophil elastase by impairing bacterial lateral flagellar system, leading to reduced colonization ofAeromonasand subsequent enrichment ofPlesiomonasdue to ecological competition of the two species. Together, we found that dietary QQ lactonase led to microbiota alteration by impairing the adaptation of commensalAeromonasto host innate immunity, which provided novel insight in the role of quorum sensing in host-microbiota interaction.
Single-nucleus analysis reveals dysregulated oxidative phosphorylation in Down syndrome basal forebrain at birth
Authors: West Nicole R. , Arachchilage Kalpana Hanthanan , Knaack Sara , Hosseini Masoumeh , Risgaard Ryan D. , MacGregor Shawn , Kumarage Pubudu , Martinez Jose L. , Wang Daifeng , Sousa Andre M.M. , Bhattacharyya Anita 
Published: February 2025

AbstractINTRODUCTIONBasal forebrain cholinergic neurons (BFCNs) are integral to learning, attention, and memory, and are prone to degeneration in Down syndrome (DS), Alzheimer’s disease, and other neurodegenerative diseases. However, the mechanisms that lead to degeneration of these neurons are not known.METHODSSingle-nuclei gene expression and ATAC sequencing were performed on postmortem human basal forebrain from unaffected control and DS tissue samples at 0-2 years of age (n=4 each).RESULTSSequencing analysis of postmortem human basal forebrain identifies gene expression differences in early postnatal DS early in life. Genes encoding proteins associated with energy metabolism pathways, specifically oxidative phosphorylation and glycolysis, and genes encoding antioxidant enzymes are upregulated in DS BFCNs.DISCUSSIONMultiomic analyses reveal that energy metabolism may be disrupted in DS BFCNs by birth. Increased oxidative phosphorylation and the accumulation of reactive oxygen species byproducts may be early contributors to DS BFCN neurodegeneration.
Functional Impact of Glycosylation and Splicing Variants of LRIG1 on EGFR Proteostasis in Cancer
Authors: Kondo Jumpei , Nagao Himari , Oyama Koki , Sakon Daisuke , Nakayama Honoka , Takamatsu Shinji , Miyoshi Eiji 
Published: February 2025

AbstractLRIG1, a membrane glycoprotein, has emerged as a significant stem cell marker and negative regulator of receptor tyrosine kinases (RTKs), including EGFR. Glycosylation is a major post-translational modification, which plays a crucial role in protein function and stability. In cancer biology, abnormal glycosylation can serve as a biomarker and contribute to pathogenesis. We aimed to investigate the effects of glycosylation on LRIG1 functions. Through database analysis and experimental approaches, we focused on evolutionarily conserved glycosylation sites of LRIG1, particularly N74 in humans. We found that a mutation of the N74 glycosylation site (N74Q) enhances LRIG1’s binding to EGFR and promotes EGFR degradation. Furthermore, we identified a naturally occurring splice variant of LRIG1 lacking exon 2, which includes the N74 site, that shows similar enhanced EGFR binding and degradation. Analysis of TCGA data revealed that exon 2 skipping in LRIG1 occurs in various cancers, with higher levels correlating with poorer survival in breast and ovarian cancers. Our findings suggest that the absence of glycosylation at N74 enhances LRIG1-EGFR binding, providing an example of glycosylation negatively regulating protein-protein interaction. This mechanism, achieved through alternative splicing, provides insights into the importance of glycosylation deficiency in cancer biology.