bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of the Type 6 Secretion System to Apoptosis and Macrophage Polarization DuringBurkholderia pseudomalleiInfection
Authors: Stockton Jacob L. , Khakhum Nittaya , Torres Alfredo G. 
Published: March 2024

AbstractBurkholderia pseudomallei(Bpm) is the causative agent of the disease melioidosis. As a facultative intracellular pathogen,Bpmhas a complex lifestyle that culminates in cell-to-cell fusion and multinucleated giant cells (MNGCs) formation. The virulence factor responsible for MNGC formation is the type 6 secretion system (T6SS), a contractile nanomachine. MNGC formation is a cell-to-cell spread strategy that allows the bacteria to avoid the extracellular immune system and our previous data highlighted cell death, apoptosis, and inflammation as pathways significantly impacted by T6SS activity. Thusly, we investigated how the T6SS influences these phenotypes within the macrophage and pulmonary models of infection. Here we report that the T6SS is responsible for exacerbating apoptotic cell death during infection in both macrophages and the lungs of infected mice. We also demonstrate that although the T6SS does not influence differential macrophage polarization, the M2 polarization observed is potentially beneficial forBpmpathogenesis and replication. Finally, we show that the T6SS contributes to the severity of inflammatory nodule formation in the lungs, which might be potentially connected to the amount of apoptosis that is triggered by the bacteria.
Freeing P300-Based Brain-Computer Interfaces from Daily Calibration by Extracting Daily Common ERPs
Authors: Heo Dojin , Kim Sung-Phil 
Published: March 2024

AbstractWhen people use brain-computer interfaces (BCIs) based on event-related potentials (ERPs) over different days, they often need to repeatedly calibrate BCIs every day using ERPs acquired on the same day. This cumbersome recalibration procedure would make it difficult to use BCIs on a daily basis. We aim to address the daily calibration issue by examining across-day variation of the BCI performance and proposing a method to avoid daily calibration. To this end, we implemented a P300-based BCI system designed to control a home appliance over five days in nineteen healthy subjects. We first examined how the BCI performance varied across days with or without daily calibration. On each day, P300-based BCIs were tested using calibration-based and calibration-free decoders (CB and CF), with a CB or a CF decoder being built on the training data on each day or those on the first day, respectively. Using the CF decoder resulted in lower BCI performance on subsequent days compared to the CB decoder. Then, we developed a method to extract daily common ERP patterns from observed ERP signals using the sparse dictionary learning algorithm. We applied this method to the CF decoder and retested the BCI performance over days. Using the proposed method improved the CF decoder performance on subsequent days; the performance was closer to the level of the CB decoder, with improvement of accuracy by 2.28%, 1.93%, 1.75%, and 3.86 % on the subsequent four days, respectively, compared to the original CF decoder. The method proposed by our study may provide a novel approach to addressing the daily-calibration issue for P300-based BCIs, which is essential to implementing BCIs into daily life.
Focal cortical dysplasia type II-dependent maladaptive myelination in the human frontal lobe
Authors: Donkels Catharina , Huber Susanne , Demerath Theo , Scheiwe Christian , Shah Mukesch J. , Heers Marcel , Urbach Horst , Schulze-Bonhage Andreas , Prinz Marco , Häussler Ute , Vlachos Andreas , Beck Jürgen , Nakagawa Julia M. , Haas Carola A. 
Published: March 2024

AbstractFocal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of intractable epilepsy. FCDs are classified into different subtypes including FCD IIa and IIb, characterized by a blurred gray-white matter boundary or a transmantle sign indicating abnormal white matter myelination. Recently, we have shown that myelination is also compromised in the gray matter of FCD IIa of the temporal lobe. Since myelination is key for brain function which is imbalanced in epilepsy, in the current study we investigated myelination in the gray matter of FCD IIa and IIb from the frontal lobe. We found that in particular FCD IIb showed myelination disturbances such as increased numbers of myelinating oligodendrocytes (OLs) and an irregular and disorganized myelination pattern covering an enlarged area in comparison to FCD IIa and controls. Interestingly, both FCD types presented with larger axon diameters when compared to controls. A significant correlation of axon diameter and myelin sheath thickness was found for FCD IIb and controls, whereas in FCD IIa large caliber axons were less myelinated. On the level of gene expression, FCD IIb presented with a significant up-regulation of myelin-associated mRNA synthesis in comparison to FCD IIa and by enhanced binding-capacities of the transcription factor MYRF to promoters of myelin-associated genes reflecting the need for more myelin due to increased axon diameters. These data show that FCD IIa and IIb are characterized by divergent signs of maladaptive myelination which may contribute to the epileptic phenotype.Main pointsIn the gray matter of the frontal lobe, FCD IIa and FCD IIb are characterized by divergent signs of maladaptive myelination.FCD IIa presents with an ordinary radial fiber pattern, but with a reduced thickness of the myelin sheath around large diameter axons and with an attenuation of the myelin synthesis machinery.FCD IIb is characterized by an irregular and disorganized myelin fiber pattern, a higher density of myelinating oligodendrocytes and an elevated transcriptional turnover of myelin-associated genes.
Metabolic rate and foraging behaviour: A mechanistic link across body size and temperature gradients
Authors: Shokri Milad , Cozzoli Francesco , Basset Alberto 
Published: March 2024

AbstractThe mechanistic link between metabolic rate and foraging behaviour is a crucial aspect of several energy-based ecological theories. Despite its importance to ecology however, it remains unclear whether and how energy requirements and behavioural patterns are mechanistically connected. Here we aimed to assess how modes of behaviour, in terms of cumulative space use, patch selection and time spent in an experimental resource patchy environment, are influenced by the foragers’ metabolic rate (SMR) and its main determinants i.e. body mass and temperature. We tested the individual behavioural patterns and metabolic rates of a model organism, the amphipodGammarus insensibilis, across a range of body masses and temperatures. We demonstrated that body mass and temperature exert a major influence on foraging decisions and space use behaviour via their effects on metabolic rates. Individual cumulative space use was found to scale allometrically with body mass and exponentially with temperature, with patch giving-up time falling as body mass and temperature increased. Moreover, SMR had greater predictive power for behavioural patterns, explaining variation beyond that accounted for by body mass and temperature combined. Our results showed that cumulative space use scaled positively with Mass- and-Temperature-independent SMR (residual). Furthermore, the foraging decisions regarding patch choice and partitioning were strongly related to M-T independent SMR; individuals with higher M-T independent SMR initially preferred the most profitable patch and, as time progressed, abandoned the patch earlier compared to others. Our findings regarding the mechanistic relationship between behavioural patterns and metabolic rate across body mass and temperature shed light on higher-order energy-based ecological processes, with implications in the face of climate change.
MdfA is a novel ClpC adaptor protein that functions in the developingBacillus subtilisspore
Authors: Massoni Shawn C. , Evans Nicola J. , Hantke Ingo , Fenton Colleen , Torpey James H. , Collins Katherine M. , Krysztofinska Ewelina M. , Muench Janina H. , Thapaliya Arjun , Martínez-Lumbreras Santiago , Martin Sé Hart , Slater Celia , Wang Xinyue , Fekade Ruth , Obwar Sandra , Yin Siyu , Vazquez Alishba , Prior Christopher B. , Turgay Kürşad , Isaacson Rivka L. , Camp Amy H. 
Published: March 2024

ABSTRACTBacterial protein degradation machinery consists of chaperone-protease complexes that play vital roles in bacterial growth and development and have sparked interest as novel antimicrobial targets. ClpC-ClpP (ClpCP) is one such chaperone-protease, recruited by adaptors to specific functions in the model bacteriumBacillus subtilisand other Gram-positive bacteria including the pathogensStaphylococcus aureusandMycobacterium tuberculosis. Here we have identified a new ClpCP adaptor protein, MdfA (“Metabolic differentiation factor A”, formerly YjbA), in a genetic screen for factors that help driveB. subtilistoward metabolic dormancy during spore formation. A knockout ofmdfAstimulates gene expression in the developing spore, while aberrant expression ofmdfAduring vegetative growth is toxic. MdfA binds directly to ClpC to induce its oligomerization and ATPase activity, and this interaction is required for the in vivo effects ofmdfA. Finally, a co-crystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on theM. tuberculosisClpC1 protein where bactericidal cyclic peptides bind. Altogether our data and that of an accompanying study by Riley, Lyda and colleagues support a model in which MdfA induces ClpCP-mediated degradation of metabolic enzymes in the developing spore, helping drive it toward metabolic dormancy.
Emotion induction modulates neural dynamics during ideational originality
Authors: Khalil Radwa , Frühholz Sascha , Godde Ben 
Published: March 2024

AbstractEmotions remarkably impact our creative minds; nevertheless, a comprehensive mapping of their underlying neural mechanisms remains elusive. Therefore, we explored the influence of induced emotional states on ideational originality and its associated neural dynamics. Participants were randomly presented with three short videos with sad, neutral, and happy content. After each video, ideational originality was evaluated using the alternate uses task (AUT). Ideational originality was significantly higher after induction of the happy state than the neutral state; in contrast, there was a nonsignificant difference between the sad and neutral states. Associated neural dynamics were assessed through EEG time-frequency (TF) power and phase-amplitude coupling (PAC) analysis. Our findings suggest that emotional states elicit distinct TF and PAC profiles associated with ideational originality. Relative to baseline, gamma activity was enhanced after the neutral induction and more enhanced after the induction of a happy state but reduced after the induction of a sad state in 2-4 seconds after starting the task. Our PAC findings suggest that the attention system may be silent after the induction of a happy emotional state to load rich materials into working memory (WM) and active in the sad state to maintain these materials in WM.HighlightIdeational originality was significantly higher after the induction of a happy state than in a neutral state.Emotional states elicited distinct EEG time-frequency and phase-amplitude coupling profiles associated with ideational originality.Relative to baseline, gamma activity was enhanced in the neutral state and more robust in a happy state but reduced in a sad state 2-4 seconds after starting AUT.Enhancing ideational originality requires the induction of emotional states to suppress overlearned associations and strengthen weaker coupling associations, which is the case after the induction of a happy emotional state.
Investigation of expression of genes encoding glycogen degrading enzymes inGardnerella swidsinskiiand identification of reference genes for quantitative real-time PCR
Authors: Kim Andy , Fernando Champika , Kularatne Divanthika , Hill Janet E. 
Published: March 2024

AbstractGardnerellaspp. express and export enzymes for the breakdown of glycogen into glucose, maltose, and malto-oligosaccharides for consumption by the vaginal microbiota but how the expression of these “public goods” is affected by substrate and product levels in the environment is not known. Accurate measurement of relative gene expression using real-time quantitative PCR relies on the identification of appropriate reference genes whose expression levels remain constant under the conditions of the study. Currently, no reference genes have been identified for gene expression analysis ofGardnerellaspp. The objectives of this study were to identify reference genes and apply them in determining the relative gene expression levels of genes encoding α-amylase and α-amylase-pullulanase in media supplemented with substrate (glycogen) or a preferred product (maltotriose). Ten candidate reference genes were evaluated and analysis of Cq values from qPCR using multiple algorithms identifieduppS(encoding polyprenyl diphosphate synthase) as the top comprehensively ranked reference gene followed bygatA(encoding Asp-tRNA/Glu-tRNA amidotransferase subunit gatA). Interpretation of the Cq values for α-amylase and α-amylase-pullulanase was performed by applying these two reference genes in the calculation of relative gene expression levels. α-amylase-pullulanase gene expression was upregulated in media supplemented with 1% glycogen in comparison to media supplemented with 1% maltotriose suggesting a regulatory mechanism inG. swidsinskiithat responds to nutrient availability. No significant difference in gene expression of α-amylase was observed suggesting expression is not influenced by substrate availability. The RNA purification protocol and reference genes validated in this study will be useful in future studies of gene expression inGardnerella.ImportanceKnowledge of the factors affecting growth of vaginal microbiota is critical to understanding how vaginal dysbiosis is initiated and maintained. Overgrowth ofGardnerellaspecies includingG. swidsinskiiis a hallmark of bacterial vaginosis. These organisms break down vaginal glycogen and the products become available for uptake byGardnerellaand other microbiota. Measuring how expression of genes encoding glycogen degrading enzymes relates to relative abundance of substrate and products in the environment requires development of protocols for RNA purification and identification of reference genes for RT-qPCR.
Spatial attention alters visual cortical representation during target anticipation
Authors: Tünçok Ekin , Carrasco Marisa , Winawer Jonathan 
Published: March 2024

ABSTRACTAttention enables us to efficiently and flexibly interact with the environment by prioritizing some image features in preparation for responding to a stimulus. Using a concurrent psychophysics– fMRI experiment, we investigated how covert spatial attention affects responses in human visual cortex prior to target onset, and how it affects subsequent behavioral performance. Performance improved at cued locations and worsened at uncued locations, relative to distributed attention, demonstrating a selective tradeoff in processing. Pre-target BOLD responses in cortical visual field maps changed in two ways: First, there was a stimulus-independent baseline shift, positive in map locations near the cued location and negative elsewhere, paralleling the behavioral results. Second, population receptive field centers shifted toward the attended location. Both effects increased in higher visual areas. Together, the results show that spatial attention has large effects on visual cortex prior to target appearance, altering neural response properties throughout and across multiple visual field maps.
Investigating the mode of action for liver toxicity and wasting-like responses produced by high dose exposures to longer chain perfluoroacid substances (PFAS) using high throughput transcriptomics
Authors: Barutcu A. Rasim , Black Michael B. , Andersen Melvin E. 
Published: March 2024

AbstractSingle doses of perfluoro-n-decanoic acid (PFDA) cause wasting, a progressive loss of 30 to 50% body weight, increasing liver/body weight ratios, and death within several weeks (Olson and Andersen, 1983). Repeat high doses of perfluorooctane sulfonate (PFOS) produce a subset of these responses in rats and monkeys. The mode of action (MOA) of these wasting-like syndromes is not clear, nor is it understood if these responses are limited to a subset of perfluoroacid substances (PFAS) or a common response to high dose exposure with a larger number of PFAS. To identify pathway perturbations in liver caused by PFAS, we analyzed publishedin vitrogene expression studies from human primary liver spheroids treated with various PFAS for treatment times up to 14 days (Rowan-Carrollet al., 2021). With treatment times of 10 to 14 days, longer-chain PFAS compounds, specifically PFOS, perfluorodecane sulfonate (PFDS) and higher doses of perfluorooctanoic acid (PFOA), downregulated large numbers of genes in pathways for steroid metabolism, fatty acid metabolism and biological oxidations. Shorter chain PFAS compounds upregulated genes in pathways for fatty acid metabolism. Although PFDA was more toxic and could only be examined at 1-day of treatment, it also downregulated genes for lipid metabolism, steroid metabolism, and biological oxidations. Shorter chain PFAS, both carboxylic and sulfonic acids, did not lead to downregulation of pathways for fatty acid or steroid metabolism. TCDD is also known to cause wasting responses in rodents and humans. In intact rats, high dose responses of longer chain PFAS produce downregulation of batteries of genes associated with fatty acid oxidation and lipogenesis similar to those seen with TCDD. Based on our results, when combined with other literature, we propose that the longer-chain PFAS impair lipogenic pathways through inhibitory interactions between PPARβ, PPARα and PPARγ.
Individualized fMRI neuromodulation enhances visuospatial perception: a guided approach targeted towards the neuro-rehabilitation of cortical blindness and deceleration of subjective cognitive impairment
Authors: Allam Anthony , Allam Vincent , Reddy Sandy , Patel Ankit , Froudarakis Emmanouil , Rohren Eric M. , Sheth Sameer A. , Papageorgiou T. Dorina 
Published: March 2024

AbstractNeuromodulation is a growing precision-medicine approach to modulating neural activity that can be used to treat neuropsychiatric, and general pathophysiologic conditions. We developed individualized fMRI neuromodulation (iNM) to study the mechanisms of visuospatial perception modulation with the long-term goal of applying it in low-vision patient populations having cortical blindness or visuospatial impairment preceding subjective cognitive impairment. To determine these mechanisms, we developed a direction and coherence discrimination task to engage visual perception (VP), visual imagery (VI), selective extero-intero-ceptive attention (SEIA), and motor planning (MP) networks. Participants discriminated up and down direction, at full and subthreshold coherence under iNM or control (no iNM). We determined the blood-oxygen-level-dependent (BOLD) magnitude as area under the curve (AUC) for VI, SEIA, and MP encoded networks and used a decoder to predict the stimulus from brain maps. The increased AUC BOLD magnitude under iNM across directions and coherences ranged from: 48-76% for SEIA, 26-59% for MP, 20-47% for VI, and 100% for strong VP coherences, but decreased for weak coherences. iNM increased classification performance. Our results imply a causal role of iNM-induced visuospatial mechanisms in strengthening these networks and provide a pathway for more accurate encoding models and effective treatment.
Closed-loop auditory stimulation targeting alpha and theta oscillations during REM sleep induces phase-dependent power and frequency changes
Authors: Jaramillo Valeria , Hebron Henry , Wong Sara , Atzori Giuseppe , Bartsch Ullrich , Dijk Derk-Jan , Violante Ines R. 
Published: March 2024

BackgroundAlpha and theta oscillations characterize the waking human electroencephalogram (EEG) and can be modulated by closed-loop auditory stimulation (CLAS). These oscillations also occur during rapid eye movement (REM) sleep, but whether they can be modulated by CLAS is not known.ObjectiveInvestigate whether CLAS can modulate alpha and theta oscillations during REM sleep in a targeted phase-dependent manner.MethodsWe recorded high-density EEG during an extended overnight sleep period in 18 healthy young adults. Auditory stimulation was delivered during both phasic and tonic REM sleep in alternating 6 s ON and 6 s OFF windows. During the ON windows, stimuli were phase-locked to four orthogonal phases of ongoing alpha or theta oscillations detected in a frontal electrode (Fz).ResultsDuring ON windows, the four orthogonal phases of ongoing alpha and theta oscillations were targeted with high accuracy. Alpha and theta CLAS induced phase-dependent changes in power and frequency at the target location. Frequency-specific effects were observed for alpha trough (speeding up) and rising (slowing down) and theta trough (speeding up) conditions. These phase-dependent changes of CLAS were observed during both REM sleep substages, even though the amplitude evoked by auditory stimuli which were not phase-locked was very much reduced in phasic compared to tonic REM sleep.ConclusionsThis study provides evidence that faster REM sleep rhythms can be modulated by CLAS in a phase-dependent manner. This offers a new approach to investigate how modulation of REM sleep oscillations affects the contribution of this vigilance state to brain function.Highlights- REM sleep alpha and theta oscillations can be modulated using phase-locked CLAS- Phase-dependent changes in power and frequency are observed in the target area- Phase-dependent modulation occurs in phasic and tonic REM sleepGraphical Abstract
Olfactory bulb stimulation mitigates Alzheimer’s-like disease progression
Authors: Salimi Morteza , Nazari Milad , Shahsavar Payam , Dehghan Samaneh , Javan Mohammad , Mirnajafi-Zadeh Javad , Raoufy Mohammad Reza 
Published: March 2024

AbstractBackgroundDeep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer’s disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits.AimsOur study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aβ) AD model rats.MethodsMale Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer’s-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by evaluations of histological, behavioral, and local field potential signal processing.ResultsOB stimulation counteracted Aβ plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task.ConclusionThis preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.