bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurovascular unit adjustments following chronic distress explain motivational deficits in mice
Authors: Cabeza Lidia , Mor Damien , Ramadan Bahrie , Benhora-Chabeaux Guillaume , Houdayer Christophe , Haffen Emmanuel , Peterschmitt Yvan , Etievant Adeline , Bourasset Fanchon 
Published: March 2024

AbstractBackgroundThe neurovascular unit (NVU) represents the structural and functional relationship between the neural tissue and the blood. Neurovascular dysfunction has been highlighted in neuropsychiatric afflictions, but whether it is a cause or a consequence of the pathology remains to be elucidated. Thus, to elucidate the role of the NVU on the emergence of emotional-cognitive dysfunction, it is necessary to study how its individual components associate. This study therefore aims at investigating whether the development of depressive-related loss of motivation is grounded on NVU adjustments impacting the permeability of the blood-brain barrier (BBB) and in particular, of the structural scaffolding of microvessels.MethodsAdult male C57BL/6jRj mice chronically treated with corticosterone (CORT) and showing severe motivational deficits in an operant progressive ratio (PR) schedule of reinforcement task, presented altered neural activation assessed through FosB expression in key brain regions involved in motivational processing (anterior insular cortex, basolateral amygdala, bed nucleus of the stria terminalis and ventral tegmental area). We evaluated NVU modifications through immunofluorescence staining targeting specific markers of microglia (IBA-1), endothelial tight junctions (ZO-1) and astrocytes (GFAP). The effect of chronic CORT administration on mice BBB permeability was evaluated throughin vivoperfusion of fluorescent 40 kDa Dextran.ResultsOur results highlight that where sustained neuronal activation failed, NVU modifications predict behavioural deficits in CORT-treated animals. Notably, our analyses show that NVU modifications within the ventral tegmental area are essential to understand effort-based related behavioural performance in mice, and most particularly, that the key element of microvessels’ tight junctions ZO-1 plays a pivotal role on motivation-related behavioural output.ConclusionsOur results confirm a direct role of neurovascular adaptations on emotional and cognitive behavioural performance in mice, and therefore place the NVU in a key position in the research of the biological substrate at the origin of neuropsychiatric disorders.
Functional states of prelimbic and related circuits during the acquisition of a GO/noGO task in rats
Authors: Muñoz-Redondo Carmen , Parras Gloria G. , Andreu-Sánchez Celia , Martín-Pascual Miguel Ángel , Delgado-García José M. , Gruart Agnès 
Published: March 2024

ABSTRACTGO/noGO tasks enable assessing decision-making processes and the ability to suppress a specific action according to the context. Here, rats had to discriminate between two visual stimuli (GO or noGO) shown on an iPad screen. The execution (for GO) or non-execution (for noGO) of the selected action (to touch or not the visual display) were reinforced with food. The main goal was to record and to analyze local field potentials (LFPs) collected from cortical and subcortical structures when the visual stimuli were shown on the touch screen and during the subsequent activities. Rats were implanted with recording electrodes in the prelimbic cortex, primary motor cortex, nucleus accumbens septi, basolateral amygdala, dorsolateral and dorsomedial striatum, hippocampal CA1, and mediodorsal thalamic nucleus. Spectral analyses of the collected data demonstrate that the prelimbic cortex was selectively involved in the cognitive and motivational processing of the learning task but not in the execution of reward-directed behaviors. In addition, the other recorded structures presented specific tendencies to be involved in these two types of brain activity in response to the presentation of GO or noGO stimuli. Spectral analyses, spectrograms, and coherence between the recorded brain areas indicate their specific involvement in GO vs. noGO tasks.
The Genetic Puzzle of Multicopy Genes: Challenges and Troubleshooting
Authors: Partida Vania Gabriela Sedano , Dias Henrique Moura , Portes Maria Teresa , Van Sluys Marie-Anne 
Published: March 2024

ABSTRACTBackgroundStudies with multicopy genes impose challenges related to gene redundancy and sequence similarity among copies. Recent advances in molecular biology and genomics tools associated with dedicated databases facilitate their study. Thus, the present work emphasizes the need for rigorous methodologies and standardized approaches to interpret RT-qPCR results accurately.ResultsThe present work inPhyscomitrium patensprovides a comprehensive five-step protocol, using thiamine thiazole synthase (THI1) and sucrose 6-phosphate phosphohydrolase (S6PP)genes as proof of concept, to showcase a systematic workflow for studying multicopy genes. Beyond examining genes of interest, we highlight the critical role of choosing appropriate internal controls in the analytical process for accurately interpreting gene expression patterns. We emphasized the importance of identifying the most relevant orthologous gene, recognizing the inherent challenges in determining the most functional copy for subsequent studies. Our objective is to enhance comprehension of gene redundancy by dissecting multicopy genes’ genomic landscape and its characteristics. Furthermore, we address the decision-making process surrounding the quantification of expression levels of multicopy genes.ConclusionsThe study of multicopy genes discloses early events of functional adaptation. We emphasize the significance of multicopy genes in plant biology and provide a practical protocol for their study. Plant systems are strongly influenced by light/dark cycles, and the challenges inherent to this process are acknowledged. In conclusion, our comprehensive approach aims to advance the understanding of multicopy gene dynamics, offering practical methodologies and contributing valuable insights to the scientific community.
Human long noncoding RNA,VILMIR,is induced by major respiratory viral infections and modulates the host interferon response
Authors: John Kristen , Huntress Ian , Smith Ethan , Chou Hsuan , Tollison Tammy S. , Covarrubias Sergio , Crisci Elisa , Carpenter Susan , Peng Xinxia 
Published: March 2024

ABSTRACTLong noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic datasets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus inducible lncRNA modulator of interferon response (VILMIR), that was consistently upregulated afterin vitroinfluenza infection across multiple human epithelial cell lines and influenza A virus subtypes.VILMIRwas also upregulated after SARS-CoV-2 and RSV infectionsin vitro. We experimentally confirmed the response ofVILMIRto influenza infection and interferon-beta (IFN-β) treatment in the A549 human epithelial cell line and found the expression ofVILMIRwas robustly induced by IFN-β treatment in a dose and time-specific manner. Single cell RNA-seq analysis of bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients uncovered thatVILMIRwas upregulated across various cell types including at least five immune cells. The upregulation ofVILMIRin immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-β treatment. Finally, we found that knockdown ofVILMIRexpression reduced the magnitude of host transcriptional responses to IFN-β treatment in A549 cells. Together, our results show thatVILMIRis a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.IMPORTANCEIdentifying host factors that regulate the immune response to human respiratory viral infection is critical to developing new therapeutics. Human long noncoding RNAs (lncRNAs) have been found to play key regulatory roles during biological processes, however the majority of lncRNA functions within the host antiviral response remain unknown. In this study, we identified that a previously uncharacterized lncRNA,VILMIR, is upregulated after major respiratory viral infections including influenza, SARS-CoV-2, and RSV. We demonstrated thatVILMIRis an interferon-stimulated gene that is upregulated after interferon-beta (IFN-β) in several human cell types. We also found that knockdown ofVILMIRreduced the magnitude of host transcriptional responses to IFN-β treatment in human epithelial cells. Our results reveal thatVILMIRregulates the host interferon response and may present a new therapeutic target during human respiratory viral infections.
Matrimeres are systemic nanoscale mediators of tissue integrity and function
Authors: Debnath Koushik , Qayoom Irfan , O’Donnell Steven , Ekiert Julia , Wang Can , Sanborn Mark A. , Liu Chang , Rivera Ambar , Cho Ik Sung , Saichellappa Saiumamaheswari , Toth Peter T. , Mehta Dolly , Rehman Jalees , Du Xiaoping , Gao Yu , Shin Jae-Won 
Published: March 2024

AbstractTissue barriers must be rapidly restored after injury to promote regeneration. However, the mechanism behind this process is unclear, particularly in cases where the underlying extracellular matrix is still compromised. Here, we report the discovery of matrimeres as constitutive nanoscale mediators of tissue integrity and function. We define matrimeres as non-vesicular nanoparticles secreted by cells, distinguished by a primary composition comprising at least one matrix protein and DNA molecules serving as scaffolds. Mesenchymal stromal cells assemble matrimeres from fibronectin and DNA within acidic intracellular compartments. Drawing inspiration from this biological process, we have achieved the successful reconstitution of matrimeres without cells. This was accomplished by using purified matrix proteins, including fibronectin and vitronectin, and DNA molecules under optimal acidic pH conditions, guided by the heparin-binding domain and phosphate backbone, respectively. Plasma fibronectin matrimeres circulate in the blood at homeostasis but exhibit a 10-fold decrease during systemic inflammatory injuryin vivo. Exogenous matrimeres rapidly restore vascular integrity by actively reannealing endothelial cells post-injury and remain persistent in the host tissue matrix. The scalable production of matrimeres holds promise as a biologically inspired platform for regenerative nanomedicine.
Biomass competition unifies individual and community scaling patterns
Authors: Fant Lorenzo , Ghedini Giulia 
Published: March 2024

AbstractBoth metabolism and growth scale sublinearly with body mass for most species. Ecosystems show the same sublinear scaling between production and total biomass but ecological theory cannot reconcile the existence of these nearly identical scalings at different levels of biological organization. We solve this paradox using marine phytoplankton to connect individual and ecosystem scalings across three orders of magnitude in body size and biomass. Competitive interactions determined by biomass, rather than differences in species size, slow metabolism in a consistent fashion across species that dominates over species-specific peculiarities, resulting in a unique behavior across community compositions. The allometry of ecosystem production thus emerges from this metabolic density-dependence, independently of the equilibrium state or resource regime of the system. Our findings demonstrate the mechanistic basis of ecosystem allometries, unifying aspects of physiology and ecology to explain why growth patterns are so strikingly similar across scales.
MANIPULATING MITOCHONDRIAL REACTIVE OXYGEN SPECIES ALTERS SURVIVAL IN UNEXPECTED WAYS IN ADROSOPHILAMODEL OF NEURODEGENERATION
Authors: Wodrich Andrew P. K. , Harris Brent T. , Giniger Edward 
Published: March 2024

ABSTRACTReactive oxygen species (ROS) are associated with aging and neurodegeneration, but the significance of this association remains obscure. Here, using aDrosophilamodel of age-related neurodegeneration, we probe this relationship in the pathologically relevant tissue, the brain, by quantifying three specific mitochondrial ROS and manipulating these redox species pharmacologically. Our goal is to ask whether pathology-associated changes in redox state are detrimental for survival, whether they may be beneficial responses, or whether they are simply covariates of pathology that do not alter viability. We find, surprisingly, that increasing mitochondrial H2O2correlates with improved survival. We also find evidence that drugs that alter the mitochondrial glutathione redox potential modulate survival primarily through the compensatory effects they induce rather than through their direct effects on the final mitochondrial glutathione redox potentialper se. We also find that the response to treatment with a redox-altering drug varies dramatically depending on the age at which the drug is administered, the duration of the treatment, and the genotype of the individual receiving the drug. These data have important implications for the design and interpretation of studies investigating the effect of redox state on health and disease as well as on efforts to modify the redox state to achieve therapeutic goals.
A role for δ subunit-containing GABAAreceptors on parvalbumin positive neurons in maintaining electrocortical signatures of sleep states
Authors: Lambert Peter M. , Salvatore Sofia V. , Lu Xinguo , Shu Hong-Jin , Benz Ann , Rensing Nicholas , Yuede Carla M. , Wong Michael , Zorumski Charles F. , Mennerick Steven 
Published: March 2024

AbstractGABAAreceptors containing δ subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, δ subunits are expressed on the surface of some pyramidal cells as well as on parvalbumin positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG; however, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity. After confirming a loss of functional δ mediated tonic currents in PV cells in cortical slices from mice lackingGabrdin PV+ neurons (PV δcKO), we performed EEG recordings to survey network activity across wake and sleep states. PV δcKO mice showed altered spectral content of EEG during NREM and REM sleep that was a result of increased oscillatory activity in NREM and the emergence of transient high amplitude bursts of theta frequency activity during REM. Viral reintroduction ofGabrdto PV+ interneurons in PV δcKO mice rescued REM EEG phenotypes, supporting an important role for δ subunit mediated inhibition of PV+ interneurons for maintaining normal REM cortical oscillations.Significance statementThe impact on cortical EEG of inhibition on PV+ neurons was studied by deleting a GABAAreceptor subunit selectively from these neurons. We discovered unexpected changes at low frequencies during sleep that were rescued by viral reintroduction.
Locus Coeruleus Contrast and Diffusivity: Effects of Age and Relations to Memory
Authors: Bennett Ilana J. , Langley Jason , Sun Andrew , Solis Kitzia , Seitz Aaron R. , Hu Xiaoping P. 
Published: March 2024

AbstractNeurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for the MTC and NODDI metrics interacted with sex such that larger age group differences were seen in males than females. Age group differences were also larger for DTI metrics in the rostral, and NODDI metrics in the caudal, locus coeruleus subdivision. Within older adults, however, there were no significant effects of age on any measure of locus coeruleus structure. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, and inclusion of DTI and NODDI metrics, make important and novel contributions to our understanding of the aging of locus coeruleus structure.
Proposing a Systematic Lineage Classification Below the Genotype Level for Dengue Serotypes 1 and 2
Authors: Pereira James Siqueira , Ribeiro Gabriela , de Souza Vinicius Carius , Brcko Isabela Carvalho , Ribeiro Igor Santana , De Lima Iago Trezena Tavares , Slavov Svetoslav Nanev , Sampaio Vessoni Sandra Coccuzzo , Elias Maria Carolina , Jerônimo Lima Alex Ranieri 
Published: March 2024

AbstractDengue virus (DENV), a mosquito-borne flavivirus, is causing a significant outbreak in Brazil. The recent surge in complete DENV genome sequences necessitates a standardized classification system for an improved understanding of viral dynamics and transmission patterns. Traditionally, DENV classification relies on serotypes and genotypes but lacks a consensus for sub-genotype classification. This hinders comprehensive analyses of viral diversity. We address this gap by proposing a novel lineage classification system for DENV using a semi-automatic workflow, leveraging the use of complete genome sequences to classify and re-evaluate DENV genetic diversity. This system offers a more granular classification scheme compared to current methods. The proposed hierarchical nomenclature, incorporating serotype, genotype, subgenotype, lineage, and sublineage, facilitates precise tracking of viral introductions and evolutionary events. This information might have crucial implications for public health interventions, enabling more targeted control strategies and improved monitoring of vaccine effectiveness during future outbreaks.
Ultrasound pulse repetition frequency preferentially activates different neuron populations independent of cell type
Authors: Sherman Jack , Bortz Emma , Antonio Erynne San , Tseng Hua-an , Raiff Laura , Han Xue 
Published: March 2024

AbstractTranscranial ultrasound activates mechanosensitive cellular signaling and modulates neural dynamics. Given that intrinsic neuronal activity is limited to a couple hundred hertz and often exhibits frequency preference, we examined whether pulsing ultrasound at physiologic pulse repetition frequencies (PRFs) could selectively influence neuronal activity in the mammalian brain. We performed calcium imaging of individual motor cortex neurons, while delivering 0.35 MHz ultrasound at PRFs of 10, 40, and 140 Hz in awake mice. We found that most neurons were preferentially activated by only one of the three PRFs, highlighting unique cellular effects of physiologic PRFs. Further, ultrasound evoked responses were similar between excitatory neurons and parvalbumin positive interneurons regardless of PRFs, indicating that individual cell sensitivity dominates ultrasound-evoked effects, consistent with the heterogeneous mechanosensitive channel expression we found across single neurons in mice and humans. These results highlight the feasibility of tuning ultrasound neuromodulation effects through varying PRFs.
Skull evolution and lineage diversification in endemic Malagasy carnivorans
Authors: Law Chris J. , Linden Tate J. , Flynn John J. 
Published: March 2024

AbstractMadagascar is one of the world’s foremost biodiversity hotspots with more than 90% of its species endemic to the island. Malagasy carnivorans are one of only four extant terrestrial mammalian clades endemic to Madagascar. Although there are only eight extant species, these carnivorans exhibit remarkable phenotypic and ecological diversity that is often hypothesized to have diversified through an adaptive radiation. Here, we investigated the evolution of skull diversity in Malagasy carnivorans and tested if they exhibited characteristics of convergence and an adaptive radiation. We found that their skull disparity exceeds that of any other feliform family, as their skulls vary widely and strikingly capture a large amount of the morphological variation found across all feliforms. We also found evidence of shared adaptive zones in cranial shape between euplerid subclades and felids, herpestids, and viverrids. Lastly, contrary to predictions of adaptive radiation, we found that Malagasy carnivorans do not exhibit rapid lineage diversification and only marginally faster rates of mandibular shape evolution, and to a lesser extent cranial shape evolution, compared to other feliforms. These results reveal that exceptional diversification rates are not necessary to generate the striking phenotypic diversity that evolved in carnivorans after their dispersal to and isolation on Madagascar.
Hamstrings are stretched more and faster during accelerative running compared to speed-matched constant speed running
Authors: Gurchiek Reed D. , Teplin Zachary , Falisse Antoine , Hicks Jennifer L. , Delp Scott L. 
Published: March 2024

AbstractBackgroundHamstring strain injuries are associated with significant time away from sport and high reinjury rates. Recent evidence suggests that hamstring injuries often occur during accelerative running, but investigations of hamstring mechanics have primarily examined constant speed running on a treadmill. To help fill this gap in knowledge, this study compares hamstring lengths and lengthening velocities between accelerative running and constant speed overground running.MethodsWe recorded 2 synchronized videos of 10 participants (5 female, 5 male) during 6 accelerative running trials and 6 constant speed running trials. We used OpenCap (a markerless motion capture system) to estimate body segment kinematics for each trial and a 3-dimensional musculoskeletal model to compute peak length and step-average lengthening velocity of the biceps femoris (long head) muscle-tendon unit. To compare running conditions, we used linear mixed regression models with running speed (normalized by the subject-specific maximum) as the independent variable.ResultsAt running speeds below 75% of top speed accelerative running resulted in greater peak lengths than constant speed running. For example, the peak hamstring muscle-tendon length when a person accelerated from running at only 50% of top speed was equivalent to running at a constant 88% of top speed. Lengthening velocities were greater during accelerative running at all running speeds. Differences in hip flexion kinematics primarily drove the greater peak muscle-tendon lengths and lengthening velocities observed in accelerative running.ConclusionHamstrings are subjected to longer muscle-tendon lengths and faster lengthening velocities in accelerative running compared to constant speed running. This provides a biomechanical explanation for the observation that hamstring strain injuries often occur during acceleration. Our results suggest coaches who monitor exposure to high-risk circumstances (long lengths, fast lengthening velocities) should consider the accelerative nature of running in addition to running speed.