bluuebunny/crossref_metadata_2025_split huggingface dataset:
Taking the perspective of an embodied avatar modulates the temporal dynamics of vicarious pain and pleasure: a combined Immersive Virtual Reality and EEG study
Authors: Nicolardi V. , Lisi M.P. , Mello M. , Fusaro M. , Tieri G. , Aglioti S.M. 
Published: June 2024

AbstractObserving negative and positive valence virtual stimuli can influence the onlookers’ subjective and brain reactivity. However, the relationship between vicarious pain and pleasure, observer’s perspective taking and cerebral activity remains underexplored. To address this gap, we asked 24 healthy participants to passively observe pleasant, painful, and neutral stimuli delivered to a virtual hand seen from a first-person (1PP) or third-person perspective (3PP) while undergoing time and time-frequency EEG recording. Participants reported a stronger sense of ownership over the virtual hand seen from a 1PP, rated pain and touch valence appropriately, and more intense than the neutral ones. Distinct EEG patterns emerged across early (N2, early posterior negativity, EPN), late (late positive potential, LPP) event-related potentials, and EEG power. The N2 and EPN components showed greater amplitudes for pain and pleasure than neutral stimuli, particularly in 1PP. The LPP component exhibited lower amplitudes for pleasure than pain and neutral stimuli. Further, theta-band power increased, and alpha power decreased for pain and pleasure stimuli viewed from a 1PP versus a 3PP perspective. In the ultra-late time window, we observed decreased theta, alpha, and beta-band power specifically associated with pleasure stimuli. Our study provides novel evidence that perspective-taking modulates the temporal dynamics of vicarious pain and pleasure.
Energy-based Modelling of Single Actin Filament Polymerisation Using Bond Graphs
Authors: Gawthrop Peter J. , Pan Michael , Rajagopal Vijay 
Published: June 2024

AbstractBond graphs provide an energy-based methodology for modelling complex systems in a hierarchical fashion; at the moment, the method allows biological system with both chemical and electrical subsystems to be modelled. Herein, the bond graph approach is extended to include chemomechanical transduction thus extending the range of biological systems to be modelled.Actin filament polymerisation and force generation is used as an example of chemo-mechanical transduction and it is shown that theTF(transformer) bond graph component provides a practical, and conceptually simple, alternative to the Brownian ratchet approach of Peskin, Odell, Oster & Mogilner. Furthermore it is shown that the bond graph approach leads to the same equation as the Brownian ratchet approach in the simplest case.The approach is illustrated by showing that flexibility and non-normal incidence can be modelled by simply adding additional bond graph components and that compliance leads to non-convexity of the force-velocity curve.Energy flows are fundamental to life; for this reason, the energy based approach is utilised to investigate the power transmission by the actin filament and its corresponding efficiency.The bond graph model is fitted to experimental data by adjusting model physical parameters.
FreeSurfer version-shuffling can boost brain age predictions
Authors: Korbmacher Max , Westlye Lars T. , Maximov Ivan I. 
Published: June 2024

Abstract / Key pointsThe influence of FreeSurfer version-dependent variability in reconstructed cortical features on brain age predictions is average small when varying training and test splits from the same data.FreeSurfer version differences can lead to some variability in brain age dependent on the choice of algorithm and individual differences in brain morphometry, highlighting the advantage of repeated random train-test splitting.Shuffling of differently processed FreeSurfer data dependent on the FreeSurfer version increases performance and generalizability of the brain age prediction model.
Non-additivity of the functional properties of individual P450 species and its manifestation in the effects of alcohol consumption on the metabolism of ketamine and amitriptyline
Authors: Ponraj Kannapiran , Gaither Kari A. , Singh Dilip Kumar , Davydova Nadezhda , Zhao Mengqi , Luo Shaman , Lazarus Philip , Prasad Bhagwat , Davydov Dmitri R. 
Published: June 2024

AbstractTo explore functional interconnections between multiple P450 enzymes and their manifestation in alcohol-induced changes in drug metabolism, we implemented a high-throughput study of correlations between the composition of the P450 pool and the substrate saturation profiles (SSP) of amitriptyline and ketamine in a series of 23 individual human liver microsomes preparations from donors with a known history of alcohol consumption. The SSPs were approximated with linear combinations of three Michaelis-Menten equations with globally optimizedKM(substrate affinity) values. This analysis revealed a strong correlation between the rate of ketamine metabolism and alcohol exposure. For both substrates, alcohol consumption caused a significant increase in the role of the low-affinity enzymes. The amplitudes of the kinetic components and the total rate were further analyzed for correlations with the abundance of 11 major P450 enzymes assessed by global proteomics. The maximal rate of metabolism of both substrates correlated with the abundance of CYP3A4, their predicted principal metabolizer. However, except for CYP2D6 and CYP2E1, responsible for the low-affinity metabolism of ketamine and amitriptyline, respectively, none of the other potent metabolizers of the drugs revealed a positive correlation. Instead, in the case of ketamine, we observed negative correlations with the abundances of CYP1A2, CYP2C9, and CYP3A5. For amitriptyline, the data suggest inhibitory effects of CYP1A2 and CYP2A6. Our results demonstrate the importance of functional interactions between multiple P450 species and their decisive role in the effects of alcohol exposure on drug metabolism.
Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer’s disease mouse model via enhancing neurotrophic and synaptic signaling
Authors: Taha Hash Brown , Birnbaum Allison , Matthews Ian , Aceituno Karel , Leon Jocelyne , Thorwald Max , Godoy-Lugo Jose , Cortes Constanza J. 
Published: June 2024

AbstractINTRODUCTIONSkeletal muscle regulates central nervous system (CNS) function and health, activating the muscle-to-brain axis through the secretion of skeletal muscle originating factors (‘myokines’) with neuroprotective properties. However, the precise mechanisms underlying these benefits in the context of Alzheimer’s disease (AD) remain poorly understood.METHODSTo investigate muscle-to-brain axis signaling in response to amyloid β (Aβ)- induced toxicity, we generated 5xFAD transgenic female mice with enhanced skeletal muscle function (5xFAD;cTFEB;HSACre) at prodromal (4-months old) and late (8-months old) symptomatic stages.RESULTSSkeletal muscle TFEB overexpression reduced Aβ plaque accumulation in the cortex and hippocampus at both ages and rescued behavioral neurocognitive deficits in 8- months-old 5xFAD mice. These changes were associated with transcriptional and protein remodeling of neurotrophic signaling and synaptic integrity, partially due to the CNS-targeting myokine prosaposin (PSAP).DISCUSSIONOur findings implicate the muscle-to-brain axis as a novel neuroprotective pathway against amyloid pathogenesis in AD.
The proneurogenic and microglial modulatory properties of botulinum toxin in the hippocampus of aging experimental mice
Authors: Joseph Jerly Helan Mary , Babu Deva Irakkam Mercy Priyadharshini , Kandasamy Mahesh 
Published: June 2024

AbstractThis study explored the neurogenic and microglial modulatory properties of botulinum toxin in the hippocampus of aging experimental mice. Therapeutic botulinum toxin (BoNT) treatment is widely practiced to reduce the excessive discharge of acetylcholine (ACh) in the management of aging and neurological deficits. While the production of new neurons in the adult brain contributes to cognitive functions, age-related diseases with excessive release of ACh and progressive neuroinflammation have been characterized by impaired hippocampal neurogenesis and memory loss. Therefore, we investigated the effect of BoNT on the regulation of hippocampal neurogenesis, focusing on doublecortin (DCX)-positive immature neurons in the hippocampus of aging experimental mice. We also assessed ionized calcium-binding adapter molecule 1 (Iba1)-positive microglia and the expression of cyclooxygenase (COX)-2, a key inflammatory response element, using reverse transcription polymerase chain reaction (RT-PCR). Results revealed a prominent increase in DCX-positive cells in the BoNT-treated animals compared to the control group. Additionally, the reduced number of microglia accompanied by decreased mRNA expression of COX-2 was evident in the BoNT-treated animals. These dual effects suggest that BoNT could be a promising therapeutic agent for mitigating age-related neuroregenerative decline and neuroinflammation responsible for cognitive impairments.
Bacterial Volatile Organic Compound Specialists in the Phycosphere
Authors: Padaki Vaishnavi G. , Mayali Xavier , Weber Peter K. , Giovannoni Stephen J. , Abraham Kaylene , Jacobs Kerry , Collart Lindsay , Halsey Kimberly H. 
Published: June 2024

AbstractLabile dissolved organic carbon (LDOC) in the oceans accounts for ∼¼ of marine primary production and turns over with a half-life of seconds to days, fueling one of the largest engines of microbial heterotrophic production on the planet. Volatile organic compounds (VOCs) are poorly constrained components of LDOC. Here, we detected 78m/zsignals, corresponding to unique VOCs, including petroleum hydrocarbons, totaling 18.5 nM in the culture medium of a model diatom. In five cocultures with bacteria adapted to grow with this diatom, 1 to 66 VOCs were depleted. Two of the most active VOC consumers,MarinobacterandRoseibium,contained more genes encoding VOC oxidation proteins, and attached to the diatom, suggesting VOC specialism. With NanoSIMS and stable isotope labeling, we confirmed thatMarinobacterincorporated carbon from benzene, one of the depleted VOCs detected in the co-culture. Diatom gross carbon production increased by up to 29% in the presence of VOC consumers, indicating that VOC consumption by heterotrophic bacteria in the phycosphere – a region of rapid organic carbon oxidation that surrounds phytoplankton cells – could impact global rates of gross primary production.
Ecdysteroid-dependent molting in tardigrades
Authors: Yamakawa Shumpei , Hejnol Andreas 
Published: June 2024

AbstractMolting is a defining feature of the most species-rich animal taxa, the Ecdysozoa, including arthropods, tardigrades, nematodes, and others. In pancrustaceans, such as insects and decapods, molting is regulated by the ecdysteroid (Ecd) hormone and its downstream cascade. However, whether the regulation of molting predates the emergence of the arthropods and represents an ancestral machinery of ecdysozoans remains unclear. Therefore, we investigated the role of Ecd in the molting process of the tardigradeHypsibius exemplaris. We show that the endogenous Ecd level periodically increases during the molting cycle ofH. exemplaris. The pulse treatment with exogenous Ecd induced molting while an antagonist of the Ecd receptor suppressed the molting. Our spatial and temporal gene expression analysis revealed the putative regulatory organs and Ecd downstream cascades. We demonstrate that tardigrade molting is regulated by Ecd hormone, supporting the ancestry of Ecd-dependent molting in panarthropods. Further, we were able to identify the putative neural center of molting regulation in tardigrades, which may represent an ancestral state of panarthropods homologous to the protocerebrum of pancrustaceans. Together, our results suggest that Ecd-dependent molting evolved 100 million years earlier than previously suggested.
Geospatial Analysis and Determinant Factors of Comorbidity Presence in Patients with Diabetes
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Vásquez-Romero Luisa Erika Milagros , Loayza-Castro Joan A. , Sanchez-Tamay Nataly Mayely , Gutierrez De Carrillo Carmen Inés 
Published: June 2024

AbstractIntroductionThe prevalence of diabetes mellitus (DM) has shown a significant increase in recent decades, leading to a rise in associated complications.ObjectiveTo explore the determinant factors and geographical distribution of comorbidities and their number in patients with diabetes in Peru.MethodsCross-sectional study based on a database providing detailed demographic and clinical information on DM patients affiliated with the Comprehensive Health Insurance (SIS: acronym in spanish) in Peru. The dependent variables in this study are twofold: the type of comorbidities present in DM patients and the number of comorbidities they have. Comorbidities were categorized into three groups: DM with obesity/dyslipidemia, DM with hypertension, and DM with mental health disorders. The number of comorbidities was classified as none, one, two, or three comorbidities.ResultsA total of 1,355,354 patients were included. Male patients, older individuals, and those with a longer time since diagnosis have different probabilities of presenting the comorbidities and a higher number of them. Additionally, the geospatial analysis showed apparent regional variations in the prevalence and number of comorbidities, highlighting the influence of environmental and socioeconomic factors and access to healthcare services.ConclusionsThis study identified significant demographic and clinical factors associated with comorbidities in patients with DM in Peru. These findings showed the need for personalized, region-specific diabetes management. Therefore, public health policies should adapt to meet the needs of different regions and groups. Improving healthcare access is crucial, especially where comorbidity prevalence is high. Further education programs must address diet and exercise comorbidities, focusing on vulnerable people.
Respiratory human adenovirus outbreak captured in wastewater surveillance
Authors: Kazmer Katherine R. , Ammerman Michelle L. , Edwards Elizabeth A. , Eisenberg Marisa C. , Gilbert Julie , Montgomery JoLynn P. , Pierce Virginia M. , Weinberg Jason B. , Wigginton Krista R. 
Published: June 2024

ABSTRACTAdenoviruses present challenges for traditional surveillance methods since there are more than 60 types that infect humans. Wastewater-based surveillance can supplement traditional surveillance methods for gastrointestinal-associated adenoviruses, but the ability to detect trends of respiratory-associated adenoviruses in wastewater remains unclear. We quantified human adenovirus type 4 (HAdV-4) in wastewater settled solids and compared wastewater measurements to clinical cases from an outbreak investigation beginning in late September 2023. The human adenovirus type 4 target was positively correlated with clinical cases (Spearman’s rho = 0.5470, p < 0.0001) and followed a similar trend during the outbreak. We also quantified human adenovirus types 3, 7, 14, 21, 40/41, and a pan-adenovirus assay that targets all types that infect humans. The respiratory adenoviruses comprised a small fraction of the adenoviruses in wastewater and types 40/41, which typically cause gastrointestinal disease, comprised the majority of the detected adenoviruses. The efficacy of adenovirus wastewater surveillance will depend on assay specificity and the public health action available for adenovirus types.WATER IMPACT STATEMENTCommunity adenovirus surveillance is strengthened by wastewater measurements. We evaluated the correlation between wastewater measurements and clinical cases during an outbreak of respiratory adenovirus type 4 infections on a college campus. Results indicate respiratory adenoviruses comprise a small portion of the adenoviruses measured in wastewater and the utility of adenovirus wastewater surveillance depends on the type and public health actionability.GRAPHICAL ABSTRACT
The Multifaceted Phenotype of Senescent HL-60/S4 Macrophages
Authors: Olins Ada L. , Mark Welch David , Saul Dominik , Prudovsky Igor , Olins Donald E. 
Published: June 2024

AbstractEvery cell has a multifaceted phenotype. Transcriptional analysis of functionally defined groups of genes can provide insight into this phenotypic complexity. In the present study, the mRNA transcriptome of phorbol ester (TPA) differentiated HL-60/S4 macrophage cells was scrutinized using Gene Set Enrichment Analysis (GSEA), which evaluates the strengths of various cellular phenotypes by examining the enrichment of functionally different gene sets. Employing GSEA, we obtained supporting evidence that HL-60/S4 macrophages are senescent, probably a consequence of enriched TGFβ and NOTCH signaling transcripts. There appears to be a reduction of transcripts for heterochromatin, nucleosome formation, and chromatin remodeling phenotypes. In addition, despite upregulated oxidative stress gene transcription, we observed a reduction of DNA damage and repair transcripts. GSEA indicated that transcripts for autophagy, extracellular matrix, and inflammation/inflammasomes are enriched. We also observed that the HL-60/S4 macrophage is enriched for apoptosis gene transcripts, which may promote necrotic death by pyroptosis. The long-term goal of this research direction is to see whether this complex multifaceted phenotypic pattern is shared with other types of macrophages and to determine what mechanisms might exist to coordinate these phenotypic facets within a single cell.
Optimized chemical labeling method for isolation of 8-oxoG-modified RNA, ChLoRox-Seq, identifies mRNAs enriched in oxidation and transcriptome-wide distribution biases of oxidation events post environmental stress
Authors: Burroughs Matthew R. , Sweet Philip J. , Contreras Lydia M. 
Published: June 2024

AbstractBulk increases in nucleobase oxidation, most commonly manifesting as the guanine (G) nucleobase modification 8-oxo-7,8-dihydroguanine (8-oxoG), have been linked to several disease pathologies. Elucidating the effects of RNA oxidation on cellular homeostasis is limited by a lack of effective tools for detecting specific regions modified with 8-oxoG. Building on a previously published method for studying 8-oxoG in DNA, we developed ChLoRox-Seq, which works by covalently functionalizing 8-oxoG sites in RNA with biotin. Importantly, this method enables antibody-free enrichment of 8-oxoG-containing RNA fragments for Next Generation Sequencing-based detection of modified regions transcriptome-wide. We demonstrate the high specificity of ChLoRox-Seq for functionalizing 8-oxoG over unmodified nucleobases in RNA and benchmark this specificity to a commonly used antibody-based approach. Key advantages of ChLoRox-Seq include: (1) heightened resolution of RNA oxidation regions (e.g. exon-level) and (2) lower experimental costs. By applying ChLoRox-Seq to mRNA extracted from human lung epithelial cells (BEAS-2B) after exposure to environmentally relevant stress, we observe that 8-oxoG modifications tend to cluster in regions that are G-rich and within mRNA transcripts possessing longer 5’ UTR and CDS regions. These findings provide new insight into the complex mechanisms that bias the accumulation of RNA oxidation across the transcriptome. Notably, our analysis suggests the possibility that most mRNA oxidation events are probabilistically driven and that mRNAs that possess more favorable intrinsic properties are prone to incur oxidation events at elevated rates. ChLoRox-Seq can be readily applied in future studies to identify regions of elevated RNA oxidation in any cellular model of interest.
Prevalence and environmental abundance of the elusive membrane trafficking complex TSET in five cosmopolitan eukaryotic groups
Authors: Penot-Raquin Mathias , Sivia Mandeep , Fafoumi Morenikedji , Larson Raegan , Dorrell Richard G. , Dacks Joel B. 
Published: June 2024

AbstractEukaryotic cell biology is largely understood from paradigms established on few model organisms, largely from the animal and fungi (opisthokonts) and to a lesser extent plants. These organisms, however, constitute only a small proportion of eukaryotic diversity, and the principles of their cell biology may not be universal to other, understudied but globally impactful, organisms. Intriguingly, there are cellular components that are present in diverse eukaryotes, but are not in the animals and fungi on which the best developed models of cell biology are derived. Consequently, these components are not included in the generally adopted frameworks of cellular function that are meant to explain eukaryotic biology. The membrane complex TSET is the best studied such example, well established to play a role in cell division and endocytosis in plants. It is found across eukaryotes, but is highly reduced in opisthokonts. Its general prevalence, abundance, and relevance in eukaryotic cellular activity is unclear. Here we show that TSET is encoded in genomes of five cosmopolitan and critical groups of primarily photosynthetic eukaryotes (green algae, red algae, stramenopiles, haptophytes and cryptophytes), with particular prevalence in the green algae and some stramenopile groups. A meta-analysis of published gene expression data from the model diatomPhaeodactylum tricornutumshows that this complex is coregulated with components of the endomembrane trafficking machinery. Moreover, meta-transcriptomic data fromTaraOceans reveals that TSET genes are both present and expressed by diatoms in the wild. These data suggest that TSET may be playing an important and underrecognized role in cellular activities within marine ecosystems. More broadly, the results support the idea that use of systems-level data for non-model organisms can illuminate our understanding of core principles of eukaryotic cell function, and may reveal important and under-appreciated players that deserve to be integrated into the pervasive models of cellular capacity.