bluuebunny/crossref_metadata_2025_split huggingface dataset:
T:B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity
Authors: Kolz Anna , Bauer Isabel Julia , de la Rosa Clara , Kavaka Vladyslav , Thomann Anna Sophie , Schmitz Rosa , Kerschensteiner Martin , Beltran Eduardo , Kawakami Naoto , Peters Anneli 
Published: June 2023

AbstractMeningeal ectopic lymphoid follicle-like structures (eLFs) have been described in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), but their role in CNS autoimmunity is unclear. To analyze the cellular phenotypes and interactions within these structures, we employed a Th17 adoptive transfer EAE model featuring formation of large, numerous eLFs. Single-cell transcriptomic analysis revealed that clusters of activated B cells and B1/Marginal Zone-like B cells are overrepresented in the CNS and identified B cells poised for undergoing antigen-driven germinal center (GC) reactions and clonal expansion in the CNS. Furthermore, CNS B cells showed enhanced capacity for antigen presentation and immunological synapse formation compared to peripheral B cells. To directly visualize Th17:B cell cooperation in eLFs, we labeled Th17 cells with a ratiometric calcium sensor, and tracked their interactions with tdTomato-labeled B cells in real-time. Thereby, we demonstrated for the first time that T and B cells form long-lasting antigen-specific contacts in meningeal eLFs that result in reactivation of autoreactive T cells. Consistent with these findings, autoreactive T cells depended on CNS B cells to maintain a pro-inflammatory cytokine profile in the CNS. Collectively, our study reveals that extensive T:B cell cooperation occurs in meningeal eLFs in our model promoting differentiation and clonal expansion of B cells, as well as reactivation of CNS T cells and thereby supporting smoldering inflammatory processes within the CNS compartment. Our results provide valuable insights into the function of eLFs and may provide a direction for future research in MS.
Decoding Arbitrary and Informed Decisions from Intracranial Recordings in Humans
Authors: Marras Laura , Verwoert Maxime , Ottenhoff Maarten C. , Goulis Sophocles , van Dijk Johannes P. , Tousseyn Simon , Wagner Louis , Colon Albert J. , Kubben Pieter L. , Janssen Marcus L.F. , Herff Steffen A. , Herff Christian 
Published: June 2023

AbstractIdeally, decisions are made based on prior knowledge, which allows for informed choices. Real life, however, often requires us to make decisions arbitrarily, without sufficient information. Decoding decision making processes from neural activity could allow for cognitive neuroprostheses and Brain-Computer Interfaces (BCIs) to support decision processes in rapid human-machine interactions, weigh decision-making confidence, and further enable neuromodulation protocols for the treatment of reward-related dysfunctions. To understand the differences between the decision-making processes in arbitrary and informed decisions, we recorded intracranial electroencephalography in a large number of cortical and subcortical areas from 5 patients during a categorization task. We demonstrate that individual decisions can be decoded from Local Field Potentials (LFPs) before motor response, in both arbitrary and informed conditions. Our analysis revealed dissimilar spatio-temporal patterns between arbitrary and informed decision-making, with arbitrary decisions being decodable in fewer brain regions and earlier in time compared to informed decisions.
241,000 to 335,000 Years Old Rock Engravings Made byHomo nalediin the Rising Star Cave system, South Africa
Authors: Berger Lee R. , Hawks John , Fuentes Agustin , van Rooyen Dirk , Tsikoane Mathabela , Ramalepa Maropeng , Nkwe Samuel , Molopyane Keneiloe 
Published: June 2023

AbstractThe production of painted, etched or engraved designs on cave walls or other surfaces is recognized as a major cognitive step in human evolution. Such intentional designs, which are widely interpreted as signifying, recording, and transmitting information in a durable manner were once considered exclusive to Late PleistoceneHomo sapiens. Recent work has demonstrated that other hominin groups also made such marks, including Neanderthals (Rodríguez-Vidal et al., 2014; Hoffmann et al., 2018), and possibly Middle-PleistoceneHomo erectus(Joordens et al., 2015). Such durable signs indicate an intentionality characteristic of meaning-making (Kissel and Fuentes 2018) which has been argued to require significant levels of cognitive abilities not found in species with smaller brain sizes (Parkington, 2010). In fact, the evolution of such meaning-making symbols is thought to be a core aspect of what it means to be “human” (Henshilwood, 2009). Here we present the first known example of abstract patterns and shapes engraved within the Dinaledi subsystem of the Rising Star Cave in South Africa. We identified markings incised into the dolomitic limestone walls of the cave. The engravings described here are deeply impressed cross-hatchings and other geometric shapes. The surfaces bearing these engravings appear to have been prepared and smoothed. In some areas there is residue that creates a sheen on the surface possibly indicating repeated handling or rubbing of the rock, and there is evidence of the application of dirt or sand to the surface by non-natural processes.Homo naledientered this part of the cave system and buried bodies within the both the Dinaledi Chamber and adjacent Hill Antechamber between 241 and 335 ka (Dirks et al., 2017; Robbins et al., 2021, Berger et al, 2023a). The engravings described here are found on a pillar in the Hill Antechamber that extends into the natural fissure corridor that links the two chambers and we associate them withH. naledi.
Structural Insights into Regulation of Insulin Expression Involving i-Motif DNA Structures in the Insulin-Linked Polymorphic Region
Authors: Guneri Dilek , Alexandrou Effrosyni , El Omari Kamel , Dvořáková Zuzana , Chikhale Rupesh V. , Pike Daniel , Waudby Christopher A. , Morris Christopher J. , Haider Shozeb , Parkinson Gary N. , Waller Zoë A. E. 
Published: June 2023

ABSTRACTThe insulin linked polymorphic region (ILPR) is a variable number of tandem repeats (VNTR) region of DNA in the promoter of the insulin gene that regulates transcription of insulin. This region is known to form the alternative DNA structures, i-motifs and G-quadruplexes. Individuals have different sequence variants of VNTR repeats and although previous work investigated the effects of some variants on G-quadruplex formation, there is not a clear picture of the relationship between the sequence diversity, the DNA structures formed, and the functional effects on insulin gene expression. Here we show that different sequence variants of the ILPR form different DNA secondary structures and insulin expression is dependent on formation of i-motif and G-quadruplex structures. The first crystal structure and dynamics of an intramolecular i-motif also reveal sequences within the loop regions forming additional stabilising interactions, which are critical to formation of the stable i-motif structures that modulate insulin expression. The outcomes of this work reveal the detail in formation of stable i-motif DNA structures, with potential for rational based drug design for compounds to alter insulin gene expression.
Insulin-like Growth Factot-1 Supplementation Promotes Kidney Development and Alleviate Renal Inflammation in Preterm Pigs
Authors: Zhong Jingren , Thymann Thomas , Sangild Per Torp , Nguyen Duc Ninh , Muk Tik 
Published: June 2023

AbstractBackgroundPreterm birth and its associated complications cause disruption of normal prenatal renal development, leading to postnatal kidney injury and failure. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a critical growth factor that stimulates tissue perfusion and development. Using necrotizing enterocolitis-sensitive preterm pigs as a model for preterm infants, we investigated whether IGF-1 supplementation during early life could improve kidney development and health.MethodsCaesarean-delivered preterm pigs were allocated into two groups, either consistently receiving vehicle or IGF-1 immediately after birth for 5, 9 or 19 days. Postnatal age-matched term pigs were selected and served as term control on postnatal day (PND) 5, 9, and 19. Blood, urine and kidney tissue were collected for biochemical, histological and gene expression analyses.ResultsPreterm pigs showed impaired kidney development and increased kidney insults, as indicated by reduced average glomerular area, increased abnormal glomeruli percentage and increased markers of renal injury and inflammation compared to term pigs. IGF-1 supplementation significantly reduced the abnormal glomeruli percentage, renal injury and inflammation related markers, and up-regulated certain maturation-related genes on PND5.ConclusionIGF-1 supplementation supports kidney maturation and restoration of kidney insults after preterm birth in the early life of newborns.ImpactPreterm birth disrupts kidney development in preterm pigs.Preterm birth leads to kidney injury and inflammation in preterm pigs.IGF-1 supplementation might promote kidney maturation and alleviate preterm birth associated kidney injury and inflammation in preterm pigs.
Modeling of lung-liver interaction during infection in a human microfluidic organ-on-a-chip
Authors: Reinhold Susanne , Herr Christian , Yao Yiwen , Pourrostami Mehdi , Ritzmann Felix , Lehr Thorsten , Selzer Dominik , Kohl Yvonne , Yildiz Daniela , Slevogt Hortense , Beisswenger Christoph , Bals Robert 
Published: June 2023

AbstractBackgroundInfections of the respiratory tract such as pneumonia or COVID-19 cause high mortality and morbidity worldwide. Organ-on-a-chip (OC) technologies have been developed in the last years to establish human-based disease models, to study basic disease mechanisms and to provide a tool to speed up drug development. The aim of this study was to establish a lung-liver microfluidic system to study the interaction of both organ modules during infection.MethodsA two organ (lung / liver) microfluidic system was established using primary human bronchial (HBECs) or alveolar type epithelial cells (ATC) for the lung module and Huh-7 cells for the liver module. Inactivated non typeableHaemophilus influenzae(NTHi) andPseudomonas aeruginosaPAO1 (PAO1) were applied to the lung module. Secreted mediators were screened by dot-blot analysis and quantified. The effect of lung epithelial bacterial stimulation on the liver cell transcriptome was analyzed by mRNA sequencing.ResultsLung and liver cells established stable cultures in a circulatory microfluidic system. Activation of HBECs or ATCs with NTHi or PAO1 resulted in the secretion of multiple inflammatory mediators into the microfluidic medium including TNF-α, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-3 (MIP-3). Addition of lung cells and application of bacterial onto the HBECs module resulted in the gross change of the transcriptome of the liver cell module. Gene ontology enrichment analysis showed the induction of various pathways involved in host defense, metabolisms, repair, and acute phase response.InterpretationIn conclusion, a two-organ lung/liver microfluidic system was established to study the interaction of the organ modules during infection. Mediators released from epithelial culture modules into the microfluidic circulation after exposure to bacterial pathogens significantly modify the gene expression patterns of liver cells.FundingThis research was funded by the German Federal Ministry of Education and Research (BMBF), 031L0153 VISION “Alternativmethoden zum Tierversuch” and the Dr. Rolf M. Schwiete Stiftung.
pi_tailtrack: A compact, inexpensive, and open-source behaviour-tracking system for head-restrained zebrafish
Authors: Randlett Owen 
Published: June 2023

AbstractQuantifying animal behavior during microscopy is crucial to associate optically recorded neural activity with behavioural outputs and states. Here I describe an imaging and tracking system for head-restrained larval zebrafish compatible with functional microscopy. This system is based on the Raspberry Pi computer, Pi NoIR camera, and open-source software for the real-time tail segmentation and skeletonization of the zebrafish tail at over 100hz. This allows for precise and long-term analyses of swimming behaviour, that can be related to functional signals recorded in individual neurons. This system offers a simple but performant solution for quantifying the behavior of head-restrained larval zebrafish, which can be built for 340€.
Predicting drug response from single-cell expression profiles of tumours
Authors: Pellecchia Simona , Viscido Gaetano , Franchini Melania , Gambardella Gennaro 
Published: June 2023

ABSTRACTDrug response prediction at the single cell level is an emerging field of research that aims to improve the efficacy and precision of cancer treatments. Here, we introduce DREEP (Drug Response Estimation from single-cell Expression Profiles), a computational method that leverages publicly available pharmacogenomic screens and functional enrichment analysis to predict single cell drug sensitivity from transcriptomic data. We validated DREEP extensivelyin vitrousing several independent single-cell datasets with over 200 cancer cell lines and showed its accuracy and robustness. Additionally, we also applied DREEP to molecularly barcoded breast cancer cells and identified drugs that can selectively target specific cell populations. DREEP provides an in-silico framework to prioritize drugs from single-cell transcriptional profiles of tumours and thus helps in designing personalized treatment strategies and accelerate drug repurposing studies. DREEP is available athttps://github.com/gambalab/DREEP.
Influence of traffic and weather on carcass persistence time of small wildlife on roads
Authors: Bénard Annaëlle , Bonenfant Christophe , Lengagne Thierry 
Published: June 2023

AbstractThe rapidly expanding road network threatens the persistence of many terrestrial species through habitat loss, fragmentation, chemical, light and noise pollution and mortality associated with wildlife-vehicle collisions. Roadkill monitoring under-estimate actual collision numbers as the time during which roadkill carcasses remain visible on the road is often shorter than the frequency of road monitoring. By placing passerines (< 20 g) and amphibian carcasses on stretches of roads we surveyed every 2 hours, we fine-tuned existing persistence estimates for these species. We found median disappearance times (time for half of the carcasses to disappear) of less than 30 minutes for birds and 1-18 hours for amphibians depending on the volume of traffic, which is much shorter than previous estimates. Rainfall did not impact carcass persistence. We show the implications of these results by (1) correcting the results of roadkill surveys performed on common toads in reproductive migration for the number of removed carcasses and (2) estimating the number of passerine-vehicle collisions in the Auvergne-Rhône-Alpes (AuRA) region of France using the citizen-science database Faune-AuRA. We estimate that a road survey conducted 3 hours after amphibian road crossing under-estimates the number of roadkill by half, and that about 6800 passerine collisions were missed in 2022 by contributors because of short carcass persistence on the road. Small-bodied carcasses are hard to detect for drivers, and for a collision-report rate of 1%, total collision numbers for passerines could be as high as 700 000 individuals from 21 reported passerine species in 2022 in AuRA.
A population-averaged structural connectomic brain atlas of 422 HCP-Aging subjects
Authors: Xiao Yiming , Lau Jonathan C. , Peters Terry , Khan Ali R. 
Published: June 2023

AbstractPopulation-averaged brain atlases, that are represented in a standard space with anatomical labels, are instrumental tools in neurosurgical planning and the study of neurodegenerative conditions. Traditional brain atlases are primarily derived from anatomical scans and contain limited information regarding the axonal organization of the white matter. With the advance of diffusion MRI that allows the modelling of fiber orientation distribution (FOD) in the brain tissue, there is an increasing interest for a population-averaged FOD template, especially based on a large healthy aging cohort, to offer structural connectivity information for connectomic surgery and analysis of neurodegeneration. The dataset described in this article contains a set of multi-contrast structural connectomic MRI atlases, including T1w, T2w, and FOD templates, along with the associated whole brain tractograms. The templates were made using multi-contrast group-wise registration based on 3T MRIs of 422 Human Connectome Project in Aging (HCP-A) subjects. To enhance the usability, probabilistic tissue maps and segmentation of 22 subcortical structures are provided. Finally, the subthalamic nucleus shown in the atlas is parcellated into sensorimotor, limbic, and associative sub-regions based on their structural connectivity to facilitate the analysis and planning of deep brain stimulation procedures. The dataset is available on the OSF Repository:https://osf.io/p7syt.Specifications tableValue of the dataThese publicly available templates were created using 422 HCP-Aging subjects, representing averaged anatomical and structural connectivity features of the healthy aging brain.Matching T1w, T2w, and fiber orientation distribution (FOD) templates are provided, together with the associated tractograms that contain 20K and 2 million streamlines.Segmentation of 22 subcortical structures and probabilistic tissue maps are provided to enhance the usability of the templates.Parcellation of the subthalamic nucleus, based on structural connectivity of the included cohort at 0.3 × 0.3 × 0.3 mm3resolution, is provided.
The 3D modules of enzyme catalysis: deconstructing active sites into distinct functional entities
Authors: Riziotis Ioannis G. , Ribeiro António J. M. , Borkakoti Neera , Thornton Janet M. 
Published: June 2023

AbstractEnzyme catalysis is governed by a limited toolkit of residues and organic or inorganic co-factors. Therefore, it is expected that recurring residue arrangements will be found across the enzyme space, which perform a defined catalytic function, are structurally similar and occur in unrelated enzymes. Leveraging the integrated information in the Mechanism and Catalytic Site Atlas (M-CSA) (enzyme structure, sequence, catalytic residue annotations, catalysed reaction, detailed mechanism description), 3D templates were derived to represent compact groups of catalytic residues. A fuzzy template-template search, allowed us to identify those recurring motifs, which are conserved or convergent, that we define as the “modules of enzyme catalysis”. We show that a large fraction of these modules facilitate binding of metal ions, co-factors and substrates, and are frequently the result of convergent evolution. A smaller number of convergent modules perform a well-defined catalytic role, such as the variants of the catalytic triad (i.e. Ser-His-Asp/Cys-His-Asp) and the saccharide-cleaving Asp/Glu triad. It is also shown that enzymes whose functions have diverged during evolution preserve regions of their active site unaltered, as shown by modules performing similar or identical steps of the catalytic mechanism. We have compiled a comprehensive library of catalytic modules, that characterise a broad spectrum of enzymes. These modules can be used as templates in enzyme design and for better understanding catalysis in 3D.
The pharmacoepigenomic landscape of cancer cell lines reveals the epigenetic component of drug sensitivity
Authors: Ohnmacht AJ , Rajamani A , Avar G , Kutkaite G , Gonçalves E , Saur D , Menden MP 
Published: June 2023

AbstractAberrant DNA methylation accompanies genetic alterations during oncogenesis and tumour homeostasis and contributes to the transcriptional deregulation of key signalling pathways in cancer. Despite increasing efforts in DNA methylation profiling of cancer patients, there is still a lack of epigenetic biomarkers to predict treatment efficacy. To address this, we analysed 721 cancer cell lines across 22 cancer types treated with 453 anti-cancer compounds. We systematically detected the predictive component of DNA methylation in the context of transcriptional and mutational patterns, i.e., in total 19 DNA methylation biomarkers across 17 drugs and five cancer types. DNA methylation constituted drug sensitivity biomarkers by mediating the expression of proximal genes, thereby enhancing biological signals across multi-omics data modalities. Our method reproduced anticipated associations, and in addition, we found that theNEK9promoter hypermethylation may confer sensitivity to the NEDD8-activating enzyme (NAE) inhibitor pevonedistat in melanoma through downregulation ofNEK9. In summary, we envision that epigenomics will refine existing patient stratification, thus empowering the next generation of precision oncology.
BrainBeats, an Open-Source EEGLAB Plugin to Jointly Analyze EEG and Cardiovascular Signals
Authors: Cannard Cédric , Wahbeh Helané , Delorme Arnaud 
Published: June 2023

ABSTRACTThe interplay between the brain and the cardiovascular systems is garnering increased attention for its potential to advance our understanding of human physiology and improve health outcomes. However, the multimodal analysis of these signals is challenging due to the lack of guidelines, standardized signal processing and statistical tools, graphical user interfaces (GUIs), and automation for processing large datasets and increasing reproducibility. A further void exists in standardized quantitative EEG (qEEG) and heart-rate variability (HRV) feature extraction methods, undermining clinical diagnostics or the robustness of machine learning (ML) models. In response to these limitations, we introduce the BrainBeats toolbox. Implemented as an open-source EEGLAB plugin, BrainBeats integrates three main protocols: 1) Heartbeat-evoked potentials (HEP) and oscillations (HEO) for assessing time-locked brain-heart interplay at the millisecond accuracy; 2) qEEG and HRV feature extraction for examining associations/differences between various brain and heart metrics or for building robust feature-based ML models; 3) Automated extraction of heart artifacts from EEG signals to remove any potential cardiovascular contamination while conducting EEG analysis. We provide a step-by-step tutorial for performing these three methods on an open-source dataset containing simultaneous 64-channel EEG, ECG, and PPG signals. Users can easily fine-tune parameters to tailor their unique research needs via the graphical user interface (GUI) or the command line. BrainBeats should make brain-heart interplay research more accessible and reproducible.SUMMARYThe BrainBeats toolbox is an open-source EEGLAB plugin designed to jointly analyze EEG and cardiovascular (ECG/PPG) signals. It offers three main protocols: heartbeat-evoked potentials (HEP) assessment, feature-based analysis, and heart artifact extraction from EEG signals. It should aid researchers and clinicians in studying brain-heart interplay through two lenses (HEP and features), enhancing reproducibility and accessibility.