bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function
Authors: Ono Kazuya , Jarysta Amandine , Hughes Natasha C. , Jukic Alma , Chang Hui Ho Vanessa , Deans Michael R. , Eatock Ruth Anne , Cullen Kathleen E. , Kindt Katie , Tarchini Basile 
Published: March 2024

ABSTRACTOtolith organs in the inner ear and neuromasts in the fish lateral-line harbor two populations of hair cells oriented to detect stimuli in opposing directions. The underlying mechanism is highly conserved: the transcription factor EMX2 is regionally expressed in just one hair cell population and acts through the receptor GPR156 to reverse cell orientation relative to the other population. In mouse and zebrafish, loss of Emx2 results in sensory organs that harbor only one hair cell orientation and are not innervated properly. In zebrafish, Emx2 also confers hair cells with reduced mechanosensory properties. Here, we leverage mouse and zebrafish models lacking GPR156 to determine how detecting stimuli of opposing directions serves vestibular function, and whether GPR156 has other roles besides orienting hair cells. We find that otolith organs inGpr156mouse mutants have normal zonal organization and normal type I-II hair cell distribution and mechano-electrical transduction properties. In contrast,gpr156zebrafish mutants lack the smaller mechanically-evoked signals that characterize Emx2-positive hair cells. Loss of GPR156 does not affect orientation-selectivity of afferents in mouse utricle or zebrafish neuromasts. Consistent with normal otolith organ anatomy and afferent selectivity,Gpr156mutant mice do not show overt vestibular dysfunction. Instead, performance on two tests that engage otolith organs is significantly altered – swimming and off-vertical-axis rotation. We conclude that GPR156 relays hair cell orientation and transduction information downstream of EMX2, but not selectivity for direction-specific afferents. These results clarify how molecular mechanisms that confer bi-directionality to sensory organs contribute to function, from single hair cell physiology to animal behavior.
Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance toPlasmodiuminfection
Authors: Matteucci Kely C. , Assis Patricia A. , Hirako Isabella C. , Leite Nathalia P. S. , Pioto Franciele , Ojelabi Ogooluwa , Toller-Kawahisa Juliana E. , Costa Diego L. , Da Silva João S. , Alves-Filho José C. , Gazzinelli Ricardo T. 
Published: March 2024

SummaryTNF has a dual effect inPlasmodiuminfection, bolstering the host’s immune defense while also triggering disease. Here, we show that TNF signaling hampers physical activity, food intake, and energy expenditure while enhancing glucose uptake by the liver and spleen as well as controlling parasitemia inP. chabaudi(Pc)-infected mice. We also demonstrate that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of HIF-1α, expression of glucose transporter GLUT1 and enhanced glycolysis in monocytic cells fromPc-infected mice. Importantly,Pc- infected iNOS-/-, TNFRΔLyz2andHIF-1αΔLyz2mice show impaired release of TNF and glycolysis in monocytes, together with increased parasitemia and disease tolerance. Together, our findings reveal that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior inPc-infected mice.
Non-invasive optoacoustic imaging visualizes exercise-induced dermal revascularization in obese mice
Authors: Huang Shan , He Hailong , Tom Robby Z. , Glasl Sarah , Anzenhofer Pia , Stiel Andre C. , Hofmann Susanna M. , Ntziachristos Vasilis 
Published: March 2024

AbstractMicrocirculatory dysfunction in dermal (dWAT) and subcutaneous white adipose tissue (scWAT) of obese humans may predict cardio-metabolic disease progression.In-vivovisualization and monitoring of microvascular remodeling in these tissues remains challenging. We compared performance of multi-spectral optoacoustic tomography (MSOT) and raster-scanning optoacoustic mesoscopy (RSOM) in visualizing lipid and hemoglobin contrast in scWAT and dWAT of diet-induced obese (DIO) mice undergoing voluntary wheel running. MSOT quantitatively visualized lipid and hemoglobin contrast in fat depots at early stages of DIO. RSOM precisely visualizes microvasculature with quantitative readouts of skin layer thickness and vascular density in dWAT and dermis. Combination of MSOT and RSOM resolved exercise-induced morphological changes in microvasculature density, tissue oxygen saturation, lipid and blood volume content in dWAT and scWAT. Combination of MSOT and RSOM precisely monitor microcirculatory dysfunction and intervention response in dWAT and scWAT of DIO mice. Our findings lay out the foundation for future clinical studies using optoacoustic-derived vascular readouts from adipose tissues as a biomarker for monitoring microcirculatory function in cardio-metabolic disease.
Unraveling Axonal Transcriptional Landscapes: Insights from iPSC-Derived Cortical Neurons and Implications for Motor Neuron Degeneration
Authors: Xu Jishu , Hörner Michaela , Nagel Maike , Perhat Perwin , Korneck Milena , Noß Marvin , Hauser Stefan , Schöls Ludger , Admard Jakob , Casadei Nicolas , Schüle Rebecca 
Published: March 2024

AbstractNeuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment specific analysis. In this study, we employ a robust RNA-sequencing (RNA-seq) approach, using microfluidic devices, to generate high-quality axonal transcriptomes from iPSC-derived cortical neurons (CNs). We achieve high specificity of axonal fractions, ensuring sample purity without contamination. Comparative analysis revealed a unique and specific transcriptional landscape in axonal compartments, characterized by diverse transcript types, including protein-coding mRNAs, RNAs encoding ribosomal proteins (RPs), mitochondrial-encoded RNAs, and long non-coding RNAs (lncRNAs). Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a set of TFs specific to the axon and indicative of their active participation in transcriptional regulation. To investigate transcripts and pathways essential for central motor neuron (MN) degeneration and maintenance we analyzedKIF1C-knockout (KO)CNs, modeling hereditary spastic paraplegia (HSP), a disorder associated with prominent length-dependent degeneration of central MN axons. We found that several key factors crucial for survival and health were absent inKIF1C-KOaxons, highlighting a possible role of these also in other neurodegenerative diseases. Taken together, this study underscores the utility of microfluidic devices in studying compartment-specific transcriptomics in human neuronal models and reveals complex molecular dynamics of axonal biology. The impact ofKIF1Con the axonal transcriptome not only deepens our understanding of MN diseases but also presents a promising avenue for exploration of compartment specific disease mechanisms.
Hemoglobin gene repertoire in teleost and cichlid fishes shaped by gene duplications and genome rearrangements
Authors: Omelchenko Dmytro , Bitja-Nyom Arnold Roger , Matschiner Michael , Malinsky Milan , Indermaur Adrian , Salzburger Walter , Bartoš Oldřich , Musilova Zuzana 
Published: March 2024

AbstractHemoglobin is a crucial element of the oxygen transport system in vertebrates. It exhibits remarkable gene diversity across teleost fishes, reflecting their evolutionary adaptations for thriving in various aquatic environments. In this study, we present the dynamic evolution of hemoglobin subunit genes based on a comparison of high quality long-read genome assemblies of 24 vertebrate species, including 16 teleosts (of which six are cichlids). Our findings indicate that teleost genomes contain between five (fugu) and 43 (salmon) hemoglobin genes, representing the largest hemoglobin gene repertoire among vertebrates. We find evidence that the ancestor of teleosts had at least four Hbα and three or four Hbβ subunit genes, and that the current gene diversity emerged during subsequent teleost radiation, driven primarily by (tandem) gene duplications, genome compaction, and rearrangement dynamics. We provide insights into the genomic organization of hemoglobin clusters, revealing the parallel origin of multiple clusters in tetrapods and in teleosts. Importantly, we show that the presence of paralogous rhbdf1 genes flanking both teleost hemoglobin clusters (LA and MN) supports the hypothesis for the origin of the LA cluster by rearrangement within teleosts, rather than by the teleost specific whole-genome duplication. We specifically focus on cichlid fishes, where adaptation to low oxygen environments has been shown to play roles in species diversification. Our analysis of six cichlid genomes, including thePungu maclarenifrom crater lake Barombi Mbo, for which we sequenced the representative genome, reveals 18 to 31 copies of the Hb genes, and elevated rates of non- synonymous substitutions compared to other teleosts. Overall, this work facilitates a deeper understanding of how hemoglobin genes contribute to the adaptive and diversification potential of teleosts.
Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice
Authors: McFadden Samuel A. , Peck Mackenzie R. , Sime Lindsey N. , Cox MaKayla F. , Ikiz Erol D. , Findley Caleigh A. , Quinn Kathleen , Fang Yimin , Bartke Andrzej , Hascup Erin R. , Hascup Kevin N. 
Published: March 2024

AbstractA thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer’s disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice. From 6-12 months of age, male and female APP/PS1 and C57BL/6 mice were chronically housed at 23 or 30°C. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and spatial cognition. Plasma, hippocampal, and peripheral (adipose, hepatic, and skeletal muscle) samples were procured postmortem and tissue-specific markers of amyloid accumulation, metabolism, and inflammation were assayed. Chronic 30°C exposure increased Tc in all groups except female APP/PS1 mice. All mice receiving thermotherapy had either improved glucose tolerance or insulin sensitivity, but the underlying processes responsible for these effects varied across sexes. In males, glucose regulation was influenced predominantly by hormonal signaling in plasma and skeletal muscle glucose transporter 4 expression, whereas in females, this was modulated at the tissue level. Thermotherapy improved spatial navigation in male C57BL/6 and APP/PS1 mice, with the later attributed to reduced hippocampal soluble amyloid-β (Aβ)42. Female APP/PS1 mice exhibited worse spatial memory recall after chronic thermotherapy. Together, the data highlights the metabolic benefits of passive thermotherapy, but future studies are needed to determine therapeutic benefits for those with AD.
Global invasion history and genomic signatures of adaptation of a highly invasive lace bug
Authors: Du Zhenyong , Wang Xuan , Duan Yuange , Liu Shanlin , Tian Li , Song Fan , Cai Wanzhi , Li Hu 
Published: March 2024

AbstractInvasive species cause enormous economic and ecological damage. Climate change has resulted in an unprecedented increase in the number and impact of invaders. The mechanisms underlying invasions, however, are largely unclear. The sycamore lace bug,Corythucha ciliata, is a highly invasive species that originated in North America. Its population has expanded over the Northern Hemisphere since the 1960s. In this study, we assemble the lace bug’s genome using high-coverage PacBio, Illumina, and Hi-C sequencing. We identify 15,278 protein-coding genes and expansion of gene families with oxidoreductase and metabolic activities. In-depth resequencing of 402 samples collected from native and nine invasive countries across three continents identified 2.74 million single nucleotide polymorphisms. We resolve two major invasion routes of this lace bug from North America through both Europe and Japan, forming a contact zone in East Asia. Genomic signatures of selection associated with invasion and long-term balancing selection in native ranges are identified. These genomic signatures overlap with each other and the expanded genes, suggesting an improvement in the oxidative stress and thermal tolerance of this species. Our findings offer valuable insights into the genomic architecture and adaptive evolution underlying the invasive capabilities of species in the face of rapid environmental changes.
Simulation of zonation-function relationships in the liver using coupled multiscale models: Application to drug-induced liver injury
Authors: Gerhäusser Steffen , Lambers Lena , Mandl Luis , Franquinet Julian , Ricken Tim , König Matthias 
Published: March 2024

AbstractMultiscale modeling requires the coupling of models on different scales, often based on different mathematical approaches and developed by different research teams. This poses many challenges, such as defining interfaces for coupling, reproducible exchange of submodels, efficient simulation of the models, or reproducibility of results. Here, we present a multiscale digital twin of the liver that couples a partial differential equation (PDE)-based porous media approach for the hepatic lobule with cellular-scale ordinary differential equation (ODE)-based models. The models based on the theory of porous media describe transport, tissue mechanical properties, and deformations at the lobular scale, while the cellular models describe hepatic metabolism in terms of drug metabolism and damage in terms of necrosis. The resulting multiscale model of the liver was used to simulate perfusion-zonation-function relationships in the liver spanning scales from single cell to the lobulus. The model was applied to study the effects of (i) protein zonation patterns (metabolic zonation) and (ii) drug concentration dependence on spatially heterogeneous liver damage in the form of necrosis. Depending on the zonation pattern, different liver damage patterns could be reproduced, including periportal and pericentral necrosis as seen in drug-induced liver injury (DILI). Increasing the drug concentration led to an increase in the observed damage pattern. A key point for the success was the integration of domain-specific simulators based on standard exchange formats, i.e., libroadrunner for the high-performance simulation of ODE-based systems and FEBio for the simulation of the continuum-biomechanical part. This allows a standardized and reproducible exchange of cellular scale models in the Systems Biology Markup Language (SBML) between research groups.
Modulation of Temporoammonic-CA1 Synapses by Neuropeptide Y is Through Y1 Receptors
Authors: Cortes Mariana A. , Bartley Aundrea F. , Li Qin , Davis Taylor R. , Cunningham Stephen E. , Perez Patric J. , Dobrunz Lynn E. 
Published: March 2024

AbstractThe reduction of neuropeptide Y (NPY), an abundant neuromodulator in the brain, has been implicated in multiple neuropsychiatric disorders, such as depression and post-traumatic stress disorder (PTSD). The CA1 region of hippocampus is an important area for anxiety and highly expresses NPY. Injection of NPY into the CA1 is anxiolytic and has been shown to alleviate behavioral symptoms in a model of traumatic stress. It is known that activation of NPY Y1 receptors has anxiolytic effects and that NPY’s anxiolytic effects in CA1 are blocked by an NPY Y1 receptor antagonist. However, the location of Y1 receptors mediating NPY’s anxiolytic effects in CA1 is not yet known. CA1 receives inputs from entorhinal cortex through the temporammonic pathway (TA), which has been shown to be important for fear learning and sensitive to stress. Our lab previously showed that NPY reduces TA-evoked synaptic responses, however, the subtype of NPY receptor mediating this effect is not yet known. In this study, we show that Y1 receptors mediate the effects of both exogenous (bath-applied) and endogenously-released NPY in the TA pathway. This is the first demonstration of a Y1 receptor-mediated effect on synaptic function in CA1. Interestingly, chronic cell-type specific overexpression of NPY impairs the sensitivity of the TA pathway to NPY and the Y1 receptor agonist. However, the effect of NPY in the Schaffer collateral (SC) pathway, which is mediate by NPY Y2 receptors, is unaffected by NPY overexpression. There are pathway-specific differences in NPY receptors that modulate NPY’s effects in CA1 and respond differently to NPY overexpression. Our results demonstrating that NPY acts at Y1 receptors in the TA pathway are consistent with the idea that the TA pathway underlies the anxiolytic effects of NPY in CA1.
Daily rhythms in metabolic and locomotor behaviour of prematurely ageing PolgA mice
Authors: Singh Amit , Yilmaz Dilara , Wehrle Esther , Kuhn Gisela A. , Müller Ralph 
Published: March 2024

AbstractAgeing is an inherent and intricate biological process that takes place in living organisms as time progresses. It involves the decline of multiple physiological functions, leading to body structure and overall performance modifications. The ageing process differs among individuals and is influenced by various factors, including lifestyle, environment, and genetic makeup. Metabolic changes and reduced locomotor activity are common hallmarks of ageing. Our study focuses on exploring these phenomena in prematurely ageing PolgA(D257A/D257A)mice (also known as PolgA) aged 41-42 weeks, as they closely mimic human ageing. We assess parameters such as oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and locomotor activity using a metabolic cage for four days and comparing them with age-matched wild-type littermates (WT). Our findings revealed that VO2, VCO2, RER, locomotor activities, water intake, and feeding behaviour show a daily rhythm, aligning with roughly a 24-hour cycle. We observed that the RER was significantly increased in PolgA mice compared to WT mice during the night-time of the light-dark cycle, suggesting a shift towards a higher reliance on carbohydrate metabolism due to more food intake during the active phase. Additionally, female PolgA mice displayed a distinct phenotype with reduced walking speed, walking distance, body weight, and grip strength in comparison to male PolgA and WT mice, indicating an early sign of ageing. Taken together, our research highlights the impact of sex-specific patterns on ageing traits in PolgA mice aged 41-42 weeks, which may be attributable to human ageing phenotypes. The unique genetic composition and accelerated ageing characteristics of PolgA mice make them invaluable in ageing studies, facilitating the investigation of underlying biological mechanisms and the identification of potential therapeutic targets for age-related diseases.
Electroencephalographic Biomarkers of Relaxation: A Systematic Review and Meta-analysis
Authors: Sugimoto Kairi , Kurashiki Hideaki , Xu Yuting , Takemi Mitsuaki , Amano Kaoru 
Published: March 2024

AbstractThe human electroencephalogram (EEG) is composed of synchronous oscillations within characteristic frequency bands, including 8–13 Hz alpha oscillations that often appear during relaxation. Relaxation is critical for physical and mental health, but the extent to which various EEG components reflect relaxation remains uncertain. This systematic review and meta-analysis investigated associations between EEG components and concurrently measured reference indices of relaxation in healthy adults. A comprehensive database search and screening using preset criteria identified 38 studies involving 1,120 participants published between January 1940 and January 2022 for qualitative synthesis. These studies used various reference relaxation measures such as electrocardiographic indices related to parasympathetic nervous system activity and introspective indices obtained through questionnaires. Risks of bias were evaluated following the risk of bias assessment tool for nonrandomized studies. A meta-analysis of 23 studies using a random-effects model revealed positive correlations between relaxation index and the power of alpha oscillations at central channels (Fisher’sz-transformed correlation coefficient and [95% confidence interval]: 0.23 [0.10–0.36]) and frontal channels (0.16 [0.02–0.31]). The correlation was significantly higher for the central channel compared with other channels. No significant correlations were detected between relaxation indices and other EEG frequencies or channels. The causal relationships between relaxation and alpha power at central and frontal channels warrant further study.
Conserved jumbo phage factors required for protein import into a phage nucleus
Authors: Kokontis Claire , Klein Timothy A , Silas Sukrit , Bondy-Denomy Joseph 
Published: March 2024

AbstractBacteriophages use diverse mechanisms to evade anti-phage defenses systems. ΦKZ-like jumbo phages assemble a proteinaceous nucleus-like compartment that excludes antagonistic host nucleases, while internalizing DNA replication and transcription machinery1,2,3,4. The phage factors required for protein import and the mechanisms of selectivity remain unknown, however. Here, we uncover an import system composed of proteins highly conserved across nucleus-forming phages, together with additional cargo-specific contributors. Using a genetic selection that forces the phage to decrease or abolish import of specific proteins, we determine that the import of five different phage nuclear-localized proteins (Nlp) all require distinct interfaces of the same factor, Imp1 (gp69). Imp1 forms discrete puncta in the phage nuclear periphery likely in complex with a direct interactor Imp6 (gp67), a conserved protein encoded nearby. The import of some proteins, including a host topoisomerase (TopA), additionally require Imp3 (gp59), a factor required for proper Imp1 function. Three additional phage proteins (Imp2, Imp4, Imp5) are also required for the import of two queried nuclear cargos, perhaps acting as specific adaptors. We therefore propose a core import system including Imp1, Imp3, and Imp6 with the highly selective Imp1 protein licensing transport through a protein lattice.