bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological Harmony or Discord? Unveiling the Correspondence Between Subjective Arousal, Valence and Physiological Responses
Authors: Koppold Alina , Lonsdorf Tina B. , Kuhn Manuel , Weymar Mathias , Ventura-Bort Carlos 
Published: June 2024

AbstractAffective experiences are inevitably accompanied by physiological changes, however it is still a matter of intense debate whether events evoking similar affective experiences produce comparable physiological responses (fingerprint hypothesis) or variation is the norm within individuals (population hypothesis). In two independent samples (N = 491; N = 64), we therefore used representational similarity analysis (RSA) to examine the trial-by-trial similarity patterns of subjective experience of valence and arousal and affect-related physiological measures (skin conductance [SCR] and startle blink responses). Across different affect-inducing tasks and samples, we observed strong-to-decisive evidence for a correspondence between SCR and startle responses and models of arousal and valence that assume variation, especially between trials generally evoking higher responses. Our results show that similar affective experiences are rather reflected by distinct physiological responses and emphasize the importance of considering intraindividual variability in future studies to better understand how physiological changes contribute to conscious affective experiences in humans.
Biodegradation Potential of Neptunomonas naphthovoran - NAG-2N-126 for Crude Oil Pollution Mitigation: Experimental and Modelling Insights
Authors: Mutallimov Turan , Wu Kejian , Deng Hai , Ibrahimov Yusif 
Published: June 2024

ABSTRACTCrude oil contamination poses a significant threat to the environment, demanding effective bioremediation strategies. While microbial biodegradation holds promise, there is a notable absence of exploration, particularly regarding the biodegradation potential of Neptunomonas naphthovoran strain NAG-2N-126. This study addresses this gap by investigating the bioremediation potential of NAG-2N-126 through experimental analyses and mathematical modelling. Our findings reveal the strain’s rapid growth on crude oil, with the microbial biomass predicted to undergo a 3.5-fold increase over the experimental period. Additionally, the strain exhibited high efficiency in degrading aromatic compounds, achieving an impressive 41% degradation rate within the initial 20-day period. Oxygen availability emerged as a critical factor influencing microbial growth and biodegradation processes, with simulations indicating a 20% decrease in degradation rates under oxygen-deprived conditions. Mathematical modelling provided insights into the complex dynamics involved, contributing to the understanding of microbial hydrocarbon degradation. However, further research is warranted to optimize growth conditions and scale up findings for practical applications in environmental cleanup efforts. By delving into this underexplored area, this study highlights the importance of NAG-2N-126 in crude oil bioremediation and underscores the need for further research to optimize its application in environmental cleanup efforts.IMPORTANCEThis study presents novel insights into microbial biodegradation of crude oil, addressing a critical environmental challenge. With an estimated 24 billion BOE potentially remaining in the North Sea reservoir and over 2,000 oil spills reported since 2011, including 215 in marine protection areas, the urgency of developing effective bioremediation strategies is paramount. By investigating the growth kinetics and biodegradation efficiency of the bacterial strain N. naphthovoran NAG-2N-126 under controlled laboratory conditions, we elucidate its potential for crude oil remediation. Our findings highlight the strain’s remarkable ability to degrade aromatic hydrocarbons, offering promise for sustainable bioremediation strategies. Furthermore, through the development of mathematical models, we provide valuable insights into microbial population dynamics and substrate utilization rates during crude oil degradation. This research contributes to advancing our understanding of bioremediation processes and offers practical implications for mitigating environmental pollution and promoting ecosystem health.
Marigold: A machine learning-based web app for zebrafish pose tracking
Authors: Teicher Gregory , Madison Riffe R. , Barnaby Wayne , Martin Gabrielle , Clayton Benjamin E. , Trapani Josef G. , Downes Gerald B. 
Published: June 2024

AbstractHigh-throughput behavioral analysis is important for drug discovery, toxicological studies, and the modeling of neurological disorders such as autism and epilepsy. Zebrafish embryos and larvae are ideal for such applications because they are spawned in large clutches, develop rapidly, feature a relatively simple nervous system, and have orthologs to many human disease genes. However, existing software for video-based behavioral analysis can be incompatible with recordings that contain dynamic backgrounds or foreign objects, lack support for multiwell formats, require expensive hardware, and/or demand considerable programming expertise. Here, we introduce Marigold, a free and open source web app for high-throughput behavioral analysis of embryonic and larval zebrafish. Marigold features an intuitive graphical user interface (GUI), tracks up to 10 user-defined keypoints, supports both single- and multiwell formats, and exports a range of kinematic parameters in addition to publication-quality data visualizations. By leveraging a highly efficient, custom-designed neural network architecture, Marigold achieves reasonable training and inference speeds even on modestly powered computers lacking a discrete graphics processing unit (GPU). Notably, as a web app, Marigold does not require any installation and runs within popular web browsers on ChromeOS, Linux, macOS, and Windows. To demonstrate Marigold’s utility, we conducted two sets of biological experiments. First, we examined novel aspects of the touch-evoked escape response intechno trousers (tnt)mutant embryos, which contain a previously described loss-of-function mutation in the gene encoding Eaat2b, a glial glutamate transporter. We identified differences and interactions between touch location (head vs. tail) and genotype. Second, we investigated the effects of feeding on larval visuomotor behavior at 5 and 7 days post-fertilization (dpf). We found differences in the number and vigor of swimming bouts between fed and unfed fish at both time points, as well as interactions between developmental stage and feeding regimen. In both biological experiments presented here, the use of Marigold facilitated novel behavioral findings. Marigold’s ease of use, robust pose tracking, amenability to diverse experimental paradigms, and flexibility regarding hardware requirements make it a powerful tool for analyzing zebrafish behavior, especially in low-resource settings such as course-based undergraduate research experiences (CUREs). Marigold is available at:https://downeslab.github.io/marigold/.
Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging
Authors: Zhuo Jiachen , Raghavan Prashant , Jiang Li , Roys Steven , Njonkou Tchoquessi Rosy Linda , Chen Hegang , Wickwire Emerson M. , Parikh Gunjan Y. , Schwartzbauer Gary T. , Grattan Lynn M. , Wang Ze , Gullapalli Rao P. , Badjatia Neeraj 
Published: June 2024

AbstractsTraumatic brain injury (TBI) even in the mild form may result in long-lasting post- concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM- ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post- concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.
Clinical Predictors of 3-Months Isoniazid Rifapentine (3HP) - Related Adverse Drug Reactions (ADR) During Tuberculosis Preventive Therapy. (PAnDoRA-3HP study): An Observational Study Protocol
Authors: Sekaggya-Wiltshire Christine , Mbabazi Irene , Nabisere-Arinaitwe Ruth , Banturaki Grace , Alinaitwe Lucy , Otalo Brian , Aber Florence , Nampala Juliet , Owor Rogers , Bayiga Josephine , Laker Agnes Odongpiny Eva , Castelnuovo Barbara , Mayito Jonathan , Sekadde Moorine , Pasipanodya Jotam G. , Turyahabwe Stavia , Zawedde-Muyanja Stella 
Published: June 2024

ABSTRACTIntroductionTuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for Tuberculosis Preventive Therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings.MethodsThis is an observational cohort study with a nested case-control study. We enrolled consecutive patients initiated on TPT using the 3HP regimen. These are followed up bi-weekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs, and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2 and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes.AnalysisThe safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. Chi-square tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modeling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.
A physical model for M1-mediated influenza A virus assembly
Authors: Peukes Julia , Dmitrieff Serge , Nédélec François J. , Briggs John A. G. 
Published: June 2024

AbstractInfluenza A virus particles assemble at the plasma membrane of infected cells. During assembly all components of the virus come together in a coordinated manner to deform the membrane into a protrusion eventually forming a new, membrane-enveloped virus. Here we integrate recent molecular insights of this process, particularly concerning the structure of the matrix protein 1 (M1), within a theoretical framework describing the mechanics of virus assembly. Our model describes M1 polymerization and membrane protrusion formation, explaining why it is efficient for M1 to form long strands assembling into helices in filamentous virions. Eventually, we find how the architecture of M1 helices is controlled by physical properties of viral proteins and the host cell membrane. Finally, by considering the growth force and speed of viral filaments, we propose that the helical geometry of M1 strands might have evolved to optimize for fast and efficient virus assembly and growth.SignificanceInfluenza A virus remains a major threat to public health. Its most abundant viral protein, matrix protein 1 (M1), forms an endoskeleton underneath the viral membrane, but how this endoskeleton contributes to the virus’ lifecycle is poorly understood. Combining cryo-electron tomography data and structural data with theoretical predictions, we explain how the energetically favorable polymerization of M1 into helical strands mediates the membrane deformations that permit the virus to exit infected cells. Our analysis of M1’s variable architecture provides insights into adaptive strategies of the virus for efficient growth under variable local conditions. The quantitative framework developed in this study could be extrapolated to other enveloped viruses and generally applied to protein-driven membrane deformations.
Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems
Authors: Lazaridis Iakovos , Crittenden Jill R. , Ahn Gun , Hirokane Kojiro , Yoshida Tomoko , Wickersham Ian R. , Mahar Ara , Skara Vasiliki , Loftus Johnny H. , Parvataneni Krishna , Meletis Konstantinos , Ting Jonathan T. , Hueske Emily , Matsushima Ayano , Graybiel Ann M. 
Published: June 2024

SUMMARYBalanced activity of canonical direct D1 and indirect D2 basal ganglia pathways is considered a core requirement for normal movement, and their imbalance is an etiologic factor in movement and neuropsychiatric disorders. We present evidence for a conceptually equivalent pair of direct-D1 and indirect-D2 pathways that arise from striatal projection neurons (SPNs) of the striosome compartment rather than from SPNs of the matrix, as do the canonical pathways. These S-D1 and S-D2 striosomal pathways target substantia nigra dopamine-containing neurons instead of basal ganglia motor output nuclei. They modulate movement oppositely to the modulation by the canonical pathways: S-D1 is inhibitory and S-D2 is excitatory. The S-D1 and S-D2 circuits likely influence motivation for learning and action, complementing and reorienting canonical pathway modulation. A major conceptual reformulation of the classic direct-indirect pathway model of basal ganglia function is needed, as well as reconsideration of the effects of D2-targeting therapeutic drugs.HIGHLIGHTSDirect S-D1 and Indirect S-D2 striosomal pathways target SNpc dopamine cellsThe S-D2 indirect pathway targets a distinct central external pallidal zone (cGPe)Stimulation of S-D2 increases, of S-D1 decreases, striatal dopamine and movementS-D1 SPNs activity brackets task, inverse to a mid-task peak of dopamine release
Dynamic regulation of NAT10-mediated mRNA acetylation at synapses by learning and memory in mouse hippocampus
Authors: Zhou Hai-Qian , Zhang Jia-Wei , Zhu Zhen , Lin Wei-Peng , Jin Hao-JY , Ding Yang-Yang , Chen Dong-Sheng , Yin Dong-Min 
Published: June 2024

AbstractPost-transcriptional modification of RNA plays important roles in regulating brain functions including learning and memory. N4-acetylcytidine (ac4C), the only known form of RNA acetylation in eukaryotes, has recently been shown to regulate mRNA stability and translation efficiency. However, the function and regulation of mRNA acetylation in the brain remain largely unknown. Here we performed ac4C dot-blots, liquid chromatography tandem mass spectrometry (LC-MS/MS), and ac4C-RNA immunoprecipitation followed by next-generation sequencing (acRIP-seq) to investigate the dynamic change of ac4C mRNA in mouse hippocampus during learning and memory. This study focused on Morris water maze (MWM), a behavioral protocol commonly used for studying hippocampus-dependent spatial learning and memory. Interestingly, the levels of ac4C mRNA were upregulated in the synaptosomes (SYN) after memory formation but returned to normal levels after memories were naturally forgotten. The protein levels of N-acetyltransferase 10 (NAT10), the ac4C writer, were also increased in the SYN after memory formation and returned to control levels after memory forgetting. Strikingly, genetic ablation of Nat10 from hippocampal neurons significantly reduced the ac4C modification of Arc, Camk2α and Grin2b mRNA and their protein levels in the SYN of training mice, which was accompanied by deficits in synaptic plasticity and behaviors of learning and memory. These results demonstrate the dynamics and roles of synaptic mRNA acetylation in learning and memory, offering insights into the epitranscriptomic regulation of brain functions. The dataset of ac4C mRNA from mouse hippocampus is accessible via the website (http://ac4catlas.com/).
Functional Complexity of Engineered Neural Networks Self-Organized on Novel 3D Interfaces
Authors: Winter-Hjelm Nicolai , Klausen Kasper Grøndahl , Normann Amund Stensrud , Sandvig Axel , Sandvig Ioanna , Sikorski Pawel 
Published: June 2024

AbstractEngineered neural networks are indispensable tools for studying neural function and dysfunction in controlled microenvironments.In vitro, neurons self-organize into complex assemblies with structural and functional similarities toin vivocircuits. Traditionally, these models are established on planar interfaces, but studies suggest that the lack of a three-dimensional growth space affects neuronal organization and function. While methods supporting 3D growth exist, reproducible 3D neuroengineering techniques compatible with electrophysiological recording methods are still needed. In this study, we developed a novel biocompatible interface made of the polymer SU-8 to support 3D network development. Using electron microscopy and immunocytochemistry, we show that neurons utilize these 3D scaffolds to self-assemble into complex, multi-layered networks. Furthermore, interfacing the scaffolds with custom microelectrode arrays enabled characterizing of electrophysiological activity. Both planar control networks and 3D networks displayed complex interactions with integrated and segregated functional dynamics. However, control networks showed stronger functional interconnections, higher entropy, and increased firing rates. In summary, our interfaces provide a versatile approach for supporting neural networks with a 3D growth environment, compatible with assorted electrophysiology and imaging techniques. This system can offer new insights into the impact of 3D topologies on neural network organization and function.
Snake venom-inspired novel peptides protectCaenorhabditis elegansagainst paraquat-induced Parkinson’s pathology
Authors: Madhubala Dev , Saikia Kangkon , Patra Aparup , Mahato Rosy , Fernandes Pedro Alexandrino , Kumar Arun , Khan Mojibur R. , Mukherjee Ashis K. 
Published: June 2024

AbstractThein vivoprotective mechanisms of two low molecular mass (∼1.4 kDa) novel custom peptides (CPs) against paraquat (PT)-induced neurodegenerative dysfunction in theCaenorhabditis elegansmodel were deciphered. CPs prevent the PT binding to the nerve ring adjacent to the pharynx inC. elegans(N2 strain) by stable and high-affinity binding to the tyrosine-protein kinase receptor CAM-1, resulting in significant inhibition of PT-induced toxicity by reducing enhanced reactive oxygen species production, mitochondrial membrane depolarization, and chemosensory dysfunction. The CPs inhibited PT-induced dopaminergic (DAergic) neuron degeneration and alpha-synuclein aggregation, the hallmarks of Parkinson’s Disease, in transgenic BZ555 and NL5901 strains ofC. elegans. The transcriptomic, functional proteomics, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses show that CPs prevented the increased expression of the genes involved in the skn-1 downstream pathway, thereby restoring PT-mediated oxidative stress, apoptosis, and neuronal damage inC.elegans. The CPs ability to repair PT-induced damage was demonstrated by a network of gene expression profiles illustrating the molecular relationships between the regulatory proteins. Further, CPs (10 mg/kg, parental route) did not show toxicity or induce inflammatory mediators in the mouse model.
DNA-directed termination of mammalian RNA polymerase II
Authors: Davidson Lee , Rouvière Jérôme O , Sousa-Luís Rui , Nojima Takayuki , Proudfoot Nicholas , Jensen Torben Heick , West Steven 
Published: June 2024

ABSTRACTThe best-studied mechanism of eukaryotic RNA polymerase II (RNAPII) transcriptional termination involves polyadenylation site-directed cleavage of the nascent RNA. The RNAPII-associated cleavage product is then degraded by XRN2, dislodging RNAPII from the DNA template. In contrast, prokaryotic RNAP and eukaryotic RNAPIII often terminate directly at T-tracts in the coding DNA strand. Here, we demonstrate a similar and omnipresent capability for mammalian RNAPII. XRN2- and T-tract-dependent termination are independent - the latter usually acting when XRN2 cannot be engaged. We show that T-tracts terminate snRNA transcription, previously thought to require the Integrator complex. Importantly, we find genome-wide termination at T-tracts in promoter-proximal regions, but not within protein-coding gene bodies. XRN2-dependent termination dominates downstream of protein-coding genes, but the T-tract process is sometimes employed. Overall, we demonstrate global DNA-directed attrition of RNAPII transcription, suggesting that RNAPs retain the potential to terminate over T-rich sequences throughout evolution.
Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain
Authors: Buck Silas A. , Mabry Samuel J. , Glausier Jill R. , Banks-Tibbs Tabitha , Ward Caroline , Gayden Kozel Jenesis , Fu Chen , Fish Kenneth N. , Lewis David A. , Logan Ryan W. , Freyberg Zachary 
Published: June 2024

AbstractAge-related dopamine (DA) neuron loss is a primary feature of Parkinson’s disease. However, it remains unclear whether similar biological processes occur during healthy aging, albeit to a lesser degree. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans. In mice, we identified no changes in midbrain neuron numbers throughout aging. Despite this, we found age-related decreases in midbrain mRNA expression of tyrosine hydroxylase (Th), the rate limiting enzyme of DA synthesis. Among midbrain glutamatergic cells, we similarly identified age-related declines in vesicular glutamate transporter 2 (Vglut2) mRNA expression. In co-transmittingTh+/Vglut2+neurons,ThandVglut2transcripts decreased with aging. Importantly, striatal Th and Vglut2 protein expression remained unchanged. In translating our findings to humans, we found no midbrain neurodegeneration during aging and identified age-related decreases inTHandVGLUT2mRNA expression similar to mouse. Unlike mice, we discovered diminished density of striatal TH+dopaminergic terminals in aged human subjects. However, TH and VGLUT2 protein expression were unchanged in the remaining striatal boutons. Finally, in contrast toThandVglut2mRNA, expression of most ribosomal genes inTh+neurons was either maintained or even upregulated during aging. This suggests a homeostatic mechanism where age-related declines in transcriptional efficiency are overcome by ongoing ribosomal translation. Overall, we demonstrate species-conserved transcriptional effects of aging in midbrain dopaminergic and glutamatergic neurons that are not accompanied by marked cell death or lower striatal protein expression. This opens the door to novel therapeutic approaches to maintain neurotransmission and bolster neuronal resilience.