bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neocortical and hippocampal theta oscillations track audiovisual integration and replay of speech memories
Authors: Biau Emmanuel , Wang Danying , Park Hyojin , Jensen Ole , Hanslmayr Simon 
Published: September 2024

ABSTRACT“Are you talkin’ to me?!” If you ever watched the masterpiece “Taxi driver” directed by Martin Scorsese, you certainly recall the famous monologue during which Travis Bickle rehearses an imaginary confrontation in front of a mirror. While remembering this scene, you recollect a myriad of speech features across visual and auditory senses with a smooth sensation of unified memory. The aim of this study was to investigate how brain oscillations integrate the fine-grained synchrony between coinciding visual and auditory features when forming multisensory speech memories. We developed a memory task presenting participants with short synchronous or asynchronous movie clips focusing on the face of speakers engaged in real interviews. In the synchronous condition, the natural alignment between visual and auditory onsets was kept intact. In the asynchronous condition, auditory onsets were delayed to present lip movements and speech sounds in antiphase specifically with respect to the theta oscillation synchronising them in the original movie. We recorded magnetoencephalographic (MEG) activity to investigate brain oscillations in response to audiovisual asynchrony in the theta band. Our results first showed that theta oscillations in the neocortex and hippocampus were modulated by the level of synchrony between lip movements and syllables during audiovisual speech perception. Second, the accuracy of subsequent theta oscillation reinstatement during memory recollection was decreased when lip movements and the auditory envelope were encoded in asynchrony during speech perception. We demonstrate that neural theta oscillations in the neocortex and the hippocampus integrated lip movements and syllables during natural speech. We conclude that neural theta oscillations play a pivotal role in both aspects of audiovisual speech memories, i.e., encoding and retrieval.
Sphingosine kinase 1 is induced by glucocorticoids in adipose derived stem cells and enhances glucocorticoid mediated signaling in adipose expansion
Authors: Lambert Johana , Kovilakath Anna , Jamil Maryam , Valentine Yolander , Anderson Andrea , Montefusco David , Cowart L. Ashley 
Published: September 2024

AbstractSphingosine kinase 1 (SphK1) plays a crucial role in regulating metabolic pathways within adipocytes and is elevated in the adipose tissue of obese mice. While previous studies have reported both pro- and inhibitory effects of SphK1 and its product, sphingosine-1-phosphate (S1P), on adipogenesis, the precise mechanisms remain unclear. This study explores the timing and downstream effects of SphK1/S1P expression and activation duringin vitroadipogenesis. We demonstrate that the synthetic glucocorticoid dexamethasone robustly induces SphK1 expression, suggesting its involvement in glucocorticoid-dependent signaling during adipogenesis. Notably, the activation of C/EBPδ, a key gene in early adipogenesis and a target of glucocorticoids, is diminished in SphK1-/- adipose-derived stem cells (ADSCs). Furthermore, glucocorticoid administration promotes adipose tissue expansion via SphK1 in a depot-specific manner. Although adipose expansion still occurs in SphK1-/- mice, it is significantly reduced. These findings indicate that while SphK1 is not essential for adipogenesis, it enhances early gene activation, thereby facilitating adipose tissue expansion.
Vestibular involvement in transcranial electrical stimulation: body sway as a marker of unintended stimulation
Authors: Laakso Ilkka , Nissi Janita , Kangasmaa Otto 
Published: September 2024

AbstractBackgroundTranscranial electrical stimulation (tES) techniques are widely used to modulate brain excitability, though their mechanisms remain unclear.ObjectiveWe aimed to demonstrate that an alternating current applied to several commonly used tES electrode montages can influence the vestibular system.MethodsBody-sway responses during alternating current stimulation at 4.6 or 4.8 Hz were measured in eight participants standing on a force platform. Sham and five active conditions, including common motor cortical tES electrode montages, were applied in a double-blind experiment.ResultsAll active conditions increased lateral body sway compared with sham at the stimulus frequency, with very large to huge effect sizes. The sway magnitude was proportional to the montage-specific electric field within the vestibular system, obtained from a computational model. The frequency and phase of the body sway were locked to the stimulus frequency and phase. An additional experiment in three participants showed that the sway response was the largest in the lower legs, similarly for both tES with a motor cortical electrode montage and an electrical vestibular stimulation montage. Together, the results suggest a direct effect of tES on the vestibular system.ConclusionUnwanted vestibular effects may interfere with the interpretation of tES studies across a wide range of typical tES frequencies and current intensities.HighlightsAlternating current stimulation produces a lateral body sway at the stimulation frequency.Larger lateral electric field in the vestibular system produces a larger sway.Several common tES montages can directly influence the vestibular system.Unwanted vestibular effects may complicate the interpretation of tES studies.
Phage-phage competition and biofilms reduce the efficacy of a combination of two virulent bacteriophages againstPseudomonas aeruginosa
Authors: Bürkle Magdalena , Korf Imke H. E. , Lippegaus Anne , Krautwurst Sebastian , Rohde Christine , Weissfuss Chantal , Nouailles Geraldine , Tene Xavière Menatong , Gaborieau Baptiste , Ghigo Jean-Marc , Ricard Jean-Damien , Hocke Andreas C. , Papenfort Kai , Debarbieux Laurent , Witzenrath Martin , Wienhold Sandra-Maria , Krishnamoorthy Gopinath 
Published: September 2024

AbstractCombined use of virulent bacteriophages (phages) and antibiotics reduces the severity of difficult-to-treatPseudomonas aeruginosainfections in many patients.In vitromethods that attempt to reproduce more than one physiological state of the pathogens can provide a valuable assessment of antibacterials like phages. Here, by measuring bacterial killing kinetics and individual replication in different growth conditions, including biofilms and a human lung epithelial cell line, we elucidated factors influencing the efficacy of two virulent phages againstP. aeruginosaPAO1. A single administration of phages effectively reduced theP. aeruginosaviability in planktonic conditions and infected human lung cell cultures, however, the emergence of phage-resistant variants occurred subsequently. In static biofilms, the phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only by combining phages and meropenem. In contrast, surface-attached biofilms exhibited tolerance to phage and/or meropenem, suggesting a spatiotemporal variation in the antibacterial effect. Moreover, the phage with the shorter lysis time lysedP. aeruginosamore rapidly and selected a specific nucleotide polymorphism that conferred a competitive disadvantage and cross-resistance to the second phage of the combination. The sequential addition of phages resulted in their unimpeded replication with no increase in bacteriolytic activity. These findings highlight biofilm developmental stages, phage-phage competition, and phage resistance as factors restricting thein vitroefficacy of a two-phage combination. Our findings provide a framework for selecting and optimizing phage combinations for enhanced efficacy againstP. aeruginosa, a metabolically flexible pathogen that undergoes specific adaptation within the infected lung.
Beyond EEG Onset Transients: Sensitisation and Habituation of Hyper-excitation to Constant Presentation and Offset of Pattern-Glare Stimuli
Authors: Jefferis Tom , Dogan Cihan , Miller Claire E. , Karathanou Maria , Tempesta Austyn J. , Schofield Andrew J. , Bowman Howard 
Published: September 2024

AbstractPattern-glare, characterised by visual distortions, discomfort, and stress when viewing striped patterns, has been associated with cortical hyperexcitability, particularly in individuals with visually induced epilepsy, migraines, and visual stress. While previous studies have explored the onset transients of such stimuli, this research investigates the sensitisation and habituation effect to the constant presentation and offset of pattern-glare stimuli. We analysed the temporal characteristics of the Event Related Potentials (ERPs) in healthy participants to find correlates of cortical hyperexcitability over two time granularities: a fine granularity (over seconds) and a coarser granularity (across the time-course of the entire experiment). We looked for habituation and sensitization effects across these time periods. Our results suggest that brain responses to pattern-glare stimuli are correlated to participants’ sensitivity to visual discomfort with statistically significant effects observed for this factor and for its interaction with changes over time. This study improves our understanding of how the brain adapts to persistent visual stimuli and provides insights that may inform treatments for conditions like migraine and epilepsy.
An inhibitor targeting glycosome membrane biogenesis killsLeishmaniaparasites
Authors: Chou Shih-En , Kalel Vishal C. , Erdmann Ralf 
Published: September 2024

AbstractLeishmaniasis is a life-threatening neglected tropical disease caused by over 20 species ofLeishmaniaparasites. Visceral leishmaniasis, also known as kala-azar, is particularly lethal, with a 95% mortality rate if left untreated. Currently, no vaccine is available, and chemotherapy remains the primary treatment option. However, these drugs have drawbacks such as high toxicities, the emergence of resistant strains, and high costs. Therefore, there is a need to develop new and safe treatments. Glycosomes are essential organelles for the survival ofLeishmaniaparasites. They are maintained by peroxin (PEX) proteins, which are responsible for glycosome biogenesis, including targeting proteins to glycosomes. Previous studies have shown that blocking the interaction between the import receptor PEX19 and the docking factor PEX3 killsTrypanosoma bruceiby disrupting glycosome biogenesis. In this study, we screened an FDA-approved drug repurposing library using an AlphaScreen based assay and identified inhibitors ofLdPEX3-LdPEX19 interactionin vitro. The inhibitor effectively killsLeishmaniaparasites, including the challenging amastigote forms contained within the infected mammalian host cells. This study validates the inhibition of glycosome biogenesis inLeishmaniaas a potential approach for developing new anti-leishmanial therapies.
Utilization and degradation of laminarin-based substrates by marine yeasts suggests their niche-specific role in microbial loop dynamics
Authors: Arslan-Gatz Berin S. , Schultz-Johansen Mikkel , Hollwedel Tom-Niklas , Niggemeier Sofie , Nimzyk Rolf , Wichels Antje , Gerdts Gunnar , Hehemann Jan-Hendrik , Harder Tilmann , Reich Marlis 
Published: September 2024

AbstractIn the oceans, the diversity of phytoplankton primary products supports a wide range of microbial heterotrophs, including bacteria and fungi. The organic substrate dynamics within pelagic microbial communities are strongly controlled by microorganismal interactions, resulting in a dense interactome. While the role of bacteria in the microbial loop is well documented, the degradation capacity and substrate specificity of marine fungi, as well as their role and function in metabolic guilds with bacteria, is comparatively less understood. We chose the polysaccharide laminarin, a major product of marine primary production, as well as oligomeric laminarin subunits and monomeric glucose, to study the degradation capacity of eleven marine yeast isolates from the pelagic microbial community of Helgoland Roads. Our aim was to measure yeast growth and correlate degradation yields and putative intermediate degradation products with the size of laminarin-based organic precursor substrates. We developed a reproducible, temporally resolved, high-throughput growth protocol to measure resource-specific yeast growth. Measurement of temporally fine-scaled growth kinetic models of isolates were accompanied with qualitative and quantitative chemical analyses of substrates and degradation intermediates. Our data showed that yeast growth was negatively correlated with oligomer length. Fluorophore-assisted carbohydrate electrophoresis suggested the lack of enzymatic endo-activity for laminarin in yeasts under investigation, suggesting they may occupy a niche in the microbial loop, benefitting from extracellular hydrolysis of carbohydrates by other microorganisms. In terrestrial environments, namely forest soil ecosystems, yeasts have been assigned a similar niche, supporting a prominent role of yeasts in microbial interactomes.
The XbnAb Cohort: 304 people with broadly neutralizing antibody activity to HIV-1
Authors: Pasin Chloé , Rusert Peter , Schmidt Daniel , Schanz Merle , Friedrich Nikolas , Abela Irene A. , Kusejko Katharina , Niklaus Cyrille , Sickmann Michèle , Weber Jacqueline , Huber Michael , Manrique Amapola , Rauch Andri , Calmy Alexandra , Cavassini Matthias , Stöckle Marcel , Notter Julia , Bernasconi Enos , Braun Dominique L. , Günthard Huldrych F. , Kouyos Roger D. , Trkola Alexandra ,   the Swiss HIV Cohort Study
Published: September 2024

AbstractBroadly neutralizing antibodies (bnAbs) recognizing a diversity of HIV-1 strains are widely thought to be essential for an HIV-1 vaccine. Extensive knowledge on bnAbs has been gained from studying natural HIV infection by following bnAb evolution in individual people with HIV (PWH). However, it remains essential to increase knowledge of bnAb responses in large PWH cohorts to assess the feasibility of inducing bnAb activity by vaccination. To allow a systematic analysis, we created the XbnAb cohort, a large bnAb-inducer cohort selected by screening plasma of PWH enrolled in the Swiss HIV Cohort Study (SHCS) and the Zurich Primary HIV Infection Study (ZPHI). The XbnAb cohort represents a retrospective, biobank-based cohort comprising data of 304 PWH who developed bnAb activity during HIV-1 infection. Here, we report on the characteristics of the XbnAb cohort and its potential for HIV vaccine research.
Epigenetic control and inheritance of rDNA arrays
Authors: Potapova Tamara , Kostos Paxton , McKinney Sean , Borchers Matthew , Haug Jeff , Guarracino Andrea , Solar Steven , Gogol Madelaine , Anez Graciela Monfort , de Lima Leonardo Gomes , Wang Yan , Hall Kate , Hoffman Sophie , Garrison Erik , Phillippy Adam M. , Gerton Jennifer L. 
Published: September 2024

AbstractRibosomal RNA (rRNA) genes exist in multiple copies arranged in tandem arrays known as ribosomal DNA (rDNA). The total number of gene copies is variable, and the mechanisms buffering this copy number variation remain unresolved. We surveyed the number, distribution, and activity of rDNA arrays at the level of individual chromosomes across multiple human and primate genomes. Each individual possessed a unique fingerprint of copy number distribution and activity of rDNA arrays. In some cases, entire rDNA arrays were transcriptionally silent. Silent rDNA arrays showed reduced association with the nucleolus and decreased interchromosomal interactions, indicating that the nucleolar organizer function of rDNA depends on transcriptional activity. Methyl-sequencing of flow-sorted chromosomes, combined with long read sequencing, showed epigenetic modification of rDNA promoter and coding region by DNA methylation. Silent arrays were in a closed chromatin state, as indicated by the accessibility profiles derived from Fiber-seq. Removing DNA methylation restored the transcriptional activity of silent arrays. Array activity status remained stable through the iPS cell re-programming. Family trio analysis demonstrated that the inactive rDNA haplotype can be traced to one of the parental genomes, suggesting that the epigenetic state of rDNA arrays may be heritable. We propose that the dosage of rRNA genes is epigenetically regulated by DNA methylation, and these methylation patterns specify nucleolar organizer function and can propagate transgenerationally.
Discovery and Functional analysis of a novelALPK1variant in ROSAH syndrome
Authors: Snelling Tom , Garnotel Leo O. , Jeru Isabelle , Tusseau Maud , Cuisset Laurence , Perlat Antoinette , Minard Geoffrey , Benquey Thibaut , Maucourant Yann , Wood Nicola T. , Cohen Philip , Ziegler Alban 
Published: September 2024

AbstractROSAH syndrome is an autosomal dominant autoinflammatory disorder characterised by visual disturbance caused by pathogenic variation in the protein kinase ALPK1. Only two such variants have been reported to cause ROSAH syndrome to date: 66 out of 67 patients harbour the Thr237Met variant, while a single patient carries a Tyr254Cys variant. Here we identify a family in which ROSAH syndrome is caused by a Ser277Phe variant inALPK1. The phenotypic variability in this family is high, with four of the seven individuals legally blind. Hypohidrosis, splenomegaly and arthritis were present in several family members. In contrast to wildtype ALPK1, which is activated specifically by the bacterial metabolite ADP-heptose during bacterial infection, ALPK1[Ser277Phe] was also activated by the human metabolites UDP-mannose and ADP-ribose, even more strongly than the ALPK1[Thr237Met] variant. However, unlike ALPK1[Thr237Met], ALPK1[Ser277Phe] could additionally be activated by GDP-mannose. These observations can explain why theseALPK1variants are active in cells in the absence of ADP-heptose and hence why patients have episodes of autoinflammation. Examination of the three-dimensional structure of ALPK1 revealed that the sidechains of Ser277 and Tyr254 interact but mutational analysis established that this interaction is not critical for the integrity of the ADP-heptose binding site. Instead, it is replacement of Ser277 by a large hydrophobic phenylalanine residue or the replacement of Tyr254 by a much smaller cysteine residue that is responsible for altering the specificity of the ADP-heptose-binding pocket. The characterisation ofALPK1variants that cause ROSAH syndrome suggests ways in which drugs that inhibit these disease-causing variants selectively can be developed.
Visual imagery of familiar people and places in category selective cortex
Authors: Scrivener Catriona L. , Teed Jessica A. , Silson Edward H. 
Published: September 2024

AbstractVisual mental imagery is a dynamic process that involves a network of multiple brain regions. We used an electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) fusion approach to ask how the neural dynamics of category selective mental imagery in EEG related to activity within medial parietal, ventral temporal, and primary visual cortex (V1). Subjects attended separate EEG and fMRI sessions where they were asked to recall personally familiar people and place stimuli. The fMRI contrast of places versus people successfully replicated previous findings of category-selectivity in the medial parietal cortex during visual recall (Silson et al., 2019), as well as other regions including the ventral and lateral place memory areas, the fusiform face area, and frontal eye fields. Using multivariate decoding analysis in pre-defined fMRI regions of interest (ROIs), we tested the hypothesis that we would be able to decode individual stimuli within the preferred category for each region. This was largely the case in the ventral temporal ROIs, but a more complex pattern emerged in the medial parietal cortex; these regions represented information during imagery that was not restricted to their preferred category. EEG-fMRI fusion indicated that the timing of both medial parietal and ventral temporal involvement peaked early on during recall but did not clearly differ from each other. However, place-selective regions generally peaked earlier than people-selective regions, suggesting that representations of place stimuli evolved more quickly for these subjects. This mirrors the results from EEG stimuli decoding, where individual places were decodable earlier in time than people. In contrast, fusion correlations in V1 occurred later during the recall period, possibly reflecting the top-down progression of mental imagery from category-selective regions to primary visual cortex.
A Novel Rapid Host Cell Entry Pathway Determines Intracellular Fate ofStaphylococcus aureus
Authors: Rühling Marcel , Schmelz Fabio , Ulbrich Kim , Wolf Julia , Pfefferle Maximilian , Moldovan Adriana , Knoch Nadine , Iwanowitsch Andreas , Kappe Christian , Paprotka Kerstin , Arenz Christoph , Fraunholz Martin J. 
Published: September 2024

AbstractStaphylococcus aureusis an opportunistic pathogen causing severe diseases. Recently,S. aureuswas recognized as intracellular pathogen with the intracellular niche promoting immune evasion and antibiotic resistance. We identified an alternative mechanism governing cellular uptake ofS. aureuswhich relies on lysosomal Ca2+, lysosomal exocytosis and occurs concurrently to other well-known entry pathways within the same host cell population. This internalization pathway is rapid and active within only few minutes after bacterial contact with host cells. Compared to slow bacterial internalization, the rapid pathway demonstrates altered phagosomal maturation as well as translocation of the pathogen to the host cytosol and ultimately results in different rates of intracellular bacterial replication and host cell death. We show that these alternative infection outcomes are caused by the mode of bacterial uptake.
Glial alterations in the glutamatergic and GABAergic signaling pathways in a mouse model of Lafora disease, a severe form of progressive myoclonus epilepsy
Authors: Viana Rosa , Rubio Teresa , Campos-Rodríguez Ángela , Sanz Pascual 
Published: September 2024

ABSTRACTLafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies (LBs), in the brain but also in peripheral tissues. It is assumed that the accumulation of LBs is related to the appearance of the characteristic pathological features of the disease. In mouse models of LD, we and others have reported an increase in the levels of reactive astrocytes and activated microglia, which triggers the expression of the different pro-inflammatory mediators. Recently, we have demonstrated that the TNF and IL-6 inflammatory signaling pathways are the main mediators of the neuroinflammatory phenotype associated with the disease. In this work, we present evidence that the activation of these pathways produces a dysregulation in the levels of different subunits of the excitatory ionotropic glutamatergic receptors (phopho-GluN2B, phospho-GluA2, GluK2) and also an increase in the levels of the GABA transporter GAT1 in the hippocampus of theEpm2b-/-mice. In addition, we present evidence of the presence of activated forms of the Src and Lyn protein kinases in this area. These effects may increase the excitatory glutamatergic signaling and decrease the inhibitory GABAergic tone, leading to hyper-excitability. More importantly, the enhanced production of these subunits occurs in non-neuronal cells such as activated microglia and reactive astrocytes, pointing out a key role of glia in the pathophysiology of LD.