bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of 30 chromosome-levelDrosophilagenome assemblies reveals dynamic evolution of centromeric satellite repeats
Authors: Gebert Daniel , Hay Amir D. , Hoang Jennifer P. , Gibbon Adam E. , Henderson Ian R. , Teixeira Felipe Karam 
Published: June 2024

AbstractTheDrosophilagenus is ideal for studying genome evolution due to its simple chromosome structure and small genome size, with rearrangements mainly restricted to within chromosome arms. However, work on the rapidly evolving repetitive genomic regions, composed of transposons and tandem repeats, have been hampered by the lack of genus-wide chromosome-level assemblies. Integrating long read genomic sequencing and chromosome capture technology, we produced and annotated 30 chromosome-level genome assemblies within theDrosophilagenus. Based on this dataset, we were able to reveal the evolutionary dynamics of genome rearrangements across theDrosophilaphylogeny, including the identification of genomic regions that show comparatively high structural stability throughout evolution. Moreover, within theananassaesubgroup, we uncovered the emergence of new chromosome conformations and the rapid expansion of novel satellite DNA sequence families which form large and continuous peri/centromeric domains with higher-order repeat structures that are reminiscent to those observed in the human andArabidopsisgenomes. These chromosome-level genome assemblies present a highly valuable resource for future research, the power of which was demonstrated by our analysis of genome rearrangements and chromosome evolution. In addition, based on our findings, we propose theananassaesubgroup as an ideal model system for studying the evolution of centromere structure.
Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward
Authors: Brida Kasey L. , Jorgensen Emily T. , Phillips Robert A. , Newman Catherine E. , Tuscher Jennifer J. , Morring Emily K. , Zipperly Morgan E. , Ianov Lara , Montgomery Kelsey D. , Tippani Madhavi , Hyde Thomas M. , Maynard Kristen R. , Martinowich Keri , Day Jeremy J. 
Published: June 2024

SummaryDrugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by theRelngene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early geneFosinReln+neurons after cocaine experience, and also revealed enrichment ofRelnmRNA inDrd1+ medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selectiveRelnknockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss ofRelnprevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.
Adolescent alcohol exposure promotes mechanical allodynia and alters synaptic function at inputs from the basolateral amygdala to the prelimbic cortex
Authors: Obray J. Daniel , Wilkes Erik T. , Scofield Michael D. , Chandler L. Judson 
Published: June 2024

AbstractBinge drinking is common among adolescents despite mounting evidence linking it to various adverse health outcomes that include heightened pain perception. The prelimbic (PrL) cortex is vulnerable to insult from adolescent alcohol exposure and receives input from the basolateral amygdala (BLA) while sending projections to the ventrolateral periaqueductal gray (vlPAG) - two brain regions implicated in nociception. In this study, adolescent intermittent ethanol (AIE) exposure was carried out in male and female rats using a vapor inhalation procedure. Assessments of mechanical and thermal sensitivity revealed that AIE exposure induced protracted mechanical allodynia. To investigate synaptic function at BLA inputs onto defined populations of PrL neurons, retrobeads and viral labelling were combined with optogenetics and slice electrophysiology. Recordings from retrobead labelled cells in the PrL revealed AIE reduced BLA driven feedforward inhibition of neurons projecting from the PrL to the vlPAG, resulting in augmented excitation/inhibition (E/I) balance and increased intrinsic excitability. Consistent with this finding, recordings from virally tagged PrL parvalbumin interneurons (PVINs) demonstrated that AIE exposure reduced both E/I balance at BLA inputs onto PVINs and PVIN intrinsic excitability. These findings provide compelling evidence that AIE alters synaptic function and intrinsic excitability within a prefrontal nociceptive circuit.
Identification of ethanol analgesia quantitative trait loci and candidate genes in BXD recombinant inbred mouse lines
Authors: Rogers Walker D. , White Alyssa , Damaj M. Imad , Miles Michael F. 
Published: June 2024

AbstractAlcohol consumption produces acute analgesic effects, and people experiencing pain conditions may drink alcohol to alleviate discomfort. However, tolerance to the analgesic properties of alcohol could prompt escalating consumption and dependence. Both nociception and alcohol-induced analgesia are under significant genetic control. Understanding the genetic architecture of these processes could inform better treatment options for people with pain conditions. This study aims to identify quantitative trait loci (QTL) driving variation in ethanol-induced analgesia across BXD recombinant inbred mouse lines. Male and female mice from 62 BXD strains received ethanol or saline oral gavage for five days and were tested for hot plate (HP) latency at baseline, Day 1, and Day 5. QTL mapping of HP phenotypes identified a significant provisional QTL on chromosome 17 for Day 1 HP latency in mice receiving ethanol. An additional highly suggestive QTL was present on chromosome 9 for the difference in pre- and post-ethanol thermal nociception. Candidate genes within QTL support intervals were provisionally identified using HP phenotypic correlations to transcriptomic database, expression QTL analysis, and other bioinformatics inquiries. The combined behavioral and bioinformatic analyses yielded strong ethanol analgesia candidate genes, specificallyMyo6. Thus, the results of this genetic study of ethanol-induced analgesia in BXD mouse strains may contribute significantly to our understanding of the molecular basis for individual variation in the analgesic response to acute ethanol.
The meninges host a unique compartment of regulatory T cells that bulwarks adult hippocampal neurogenesis
Authors: Marin-Rodero Miguel , Reyes Elisa Cintado , Walker Alec J. , Jayewickreme Teshika , Pinho-Ribeiro Felipe A. , Richardson Quentin , Jackson Ruaidhrí , Chiu Isaac M. , Benoist Christophe , Stevens Beth , Trejo José Luís , Mathis Diane 
Published: June 2024

ABSTRACTOur knowledge about the meningeal immune system has recently burgeoned, particularly our understanding of how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains sparse. This study highlights the heterogeneous and polyfunctional regulatory-T (Treg) cell compartment in the meninges. A Treg subtype specialized in controlling Th1-cell responses and another known to control responses in B-cell follicles were substantial components of this compartment, foretelling that punctual Treg-cell ablation rapidly unleashed interferon-gamma production by meningeal lymphocytes, unlocked their access to the brain parenchyma, and altered meningeal B-cell profiles. Distally, the hippocampus assumed a reactive state, with morphological and transcriptional changes in multiple glial-cell types; within the dentate gyrus, neural stem cells showed exacerbated death and desisted from further differentiation, associated with inhibition of spatial-reference memory. Thus, meningeal Treg cells are a multifaceted bulwark to brain homeostasis at steady-state.One sentence summaryA distinct population of regulatory T cells in the murine meninges safeguards homeostasis by keeping local interferon-γ-producing lymphocytes in check, thereby preventing their invasion of the parenchyma, activation of hippocampal glial cells, death of neural stem cells, and memory decay.
Event structure sculpts neural population dynamics in the lateral entorhinal cortex
Authors: Kanter Benjamin R. , Lykken Christine M. , Moser May-Britt , Moser Edvard I. 
Published: June 2024

AbstractOur experience of the world is a continuous stream of events which must be segmented and organized simultaneously at multiple timescales. The neural mechanisms underlying this process remain unknown. Here, we simultaneously recorded many hundreds of neurons in the lateral entorhinal cortex (LEC) of freely behaving rats as we manipulated event structure at multiple timescales. During foraging as well as during sleep, population activity drifted continuously and unidirectionally along a one-dimensional manifold. Boundaries between events were associated with discrete shifts in state space, suggesting that LEC dynamics directly reflect event segmentation. During tasks with a recurring temporal structure, activity traveled additionally in directions orthogonal to the flow of drift, enabling the LEC population to multiplex event information across different timescales. Taken together, these results identify a hierarchically organized neural coding scheme for segmenting and organizing events in time.
Liver-specific Mettl14 deletion induces nuclear heterotypia and dysregulates RNA export machinery
Authors: Berggren Keith A , Sinha Saloni , Lin Aaron E , Schwoerer Michael P , Maya Stephanie , Biswas Abhishek , Cafiero Thomas R , Liu Yongzhen , Gertje Hans P , Suzuki Saori , Berneshawi Andrew R. , Carver Sebastian , Heller Brigitte , Hassan Nora , Ali Qazi , Beard Daniel , Wang Danyang , Cullen John M , Kleiner Ralph E , Crossland Nicholas A , Schwartz Robert E , Ploss Alexander 
Published: June 2024

AbstractModification of RNA with N6-methyladenosine (m6A) has gained attention in recent years as a general mechanism of gene regulation. In the liver, m6A, along with its associated machinery, has been studied as a potential biomarker of disease and cancer, with impacts on metabolism, cell cycle regulation, and pro-cancer state signaling. However these observational data have yet to be causally examinedin vivo.For example, neither perturbation of the key m6A writersMettl3andMettl14, nor the m6A readersYthdf1andYthdf2have been thoroughly mechanistically characterizedin vivoas they have beenin vitro. To understand the functions of these machineries, we developed mouse models and found that deletingMettl14led to progressive liver injury characterized by nuclear heterotypia, with changes in mRNA splicing, processing and export leading to increases in mRNA surveillance and recycling.
PCM1 conveys centrosome asymmetry to polarized endosome dynamics in regulating daughter cell fate
Authors: Zhao Xiang , Wang Yiqi , Mouilleau Vincent , Solak Ahmet Can , Garcia Jason , Chen Xingye , Wilkinson Christopher J. , Royer Loic , Dong Zhiqiang , Guo Su 
Published: June 2024

AbstractVertebrate radial glia progenitors (RGPs), the principal neural stem cells, balance self-renewal and differentiation through asymmetric cell division (ACD), during which unequal inheritance of centrosomes is observed. Mechanistically, how centrosome asymmetry leads to distinct daughter cell fate remains largely unknown. Here we find that the centrosome protein Pericentriolar Material 1 (Pcm1), asymmetrically distributed at the centrosomes, regulates polarized endosome dynamics and RGP fate.In vivotime-lapse imaging and nanoscale-resolution expansion microscopy of zebrafish embryonic RGPs detect Pcm1 on Notch ligand-containing endosomes, in a complex with the polarity regulator Par-3 and dynein motor. Loss ofpcm1disrupts endosome dynamics, with clonal analysis uncovering increased neuronal production at the expense of progenitors. Pcm1 facilitates an exchange of Rab5b (early) for Rab11a (recycling) endosome markers and promotes the formation of Par-3 and dynein macromolecular complexes on recycling endosomes. Finally, in human-induced pluripotent stem cell-derived brain organoids, PCM1 shows asymmetry and co-localization with PARD3 and RAB11A in mitotic neural progenitors. Our data reveal a new mechanism by which centrosome asymmetry is conveyed by Pcm1 to polarize endosome dynamics and Notch signaling in regulating ACD and progenitor fate.
Rapid rebalancing of co-tuned ensemble activity in the auditory cortex
Authors: Kang HiJee , Babola Travis A. , Kanold Patrick O. 
Published: June 2024

AbstractSensory information is represented by small varying neuronal ensembles in sensory cortices. In the auditory cortex (AC) repeated presentations of the same sound activate differing ensembles indicating high trial-by trial variability in activity even though the sounds activate the same percept. Efficient processing of complex acoustic signals requires that these sparsely distributed neuronal ensembles actively interact in order to provide a constant percept. Thus, the differing ensembles might interact to process the incoming sound inputs. Here, we probe interactions within and across ensembles by combiningin vivo2-photon Ca2+imaging and holographic optogenetic stimulation to study how increased activity of single cells level affects the cortical network. We stimulated a small number of neurons sharing the same frequency preference alongside the presentation of a target pure tone, further increasing their tone-evoked activity. We found that other non-stimulated co-tuned neurons decreased their tone-evoked activity when the frequency of the presented pure tone matched to their tuning property, while non co-tuned neurons were unaffected. Activity decrease was greater for non-stimulated co-tuned neurons with higher frequency selectivity. Co-tuned and non co-tuned neurons were spatially intermingled. Our results shows that co-tuned ensembles communicated and balanced their total activity across the larger network. The rebalanced network activity due to external stimulation remained constant. These effects suggest that co-tuned ensembles in AC interact and rapidly rebalance their activity to maintain encoding homeostasis, and that the rebalanced network is persistent.
Diversification of the Rho transcription termination factor in bacteria
Authors: Moreira Sofia M. , Chyou Te-yuan , Wade Joseph T. , Brown Chris M. 
Published: June 2024

ABSTRACTCorrect termination of transcription is essential for gene expression. In bacteria, factor-dependent termination relies on the Rho factor, that classically has three conserved domains. Some bacteria also have a functional insertion region. However, the variation in Rho structure among bacteria has not been analyzed in detail. This study determines the distribution, sequence conservation, and predicted features of Rho factors with diverse domain architectures by analyzing 2,730 bacterial genomes. About half (49.8%) of the species analyzed have the typicalEscherichia colilike Rho while most of the other species (39.8%) have diverse, atypical forms of Rho. Besides conservation of the main domains, we describe a duplicated RNA-binding domain present in specific species and novel variations in the bicyclomycin binding pocket. The additional regions observed in Rho proteins exhibit remarkable diversity. Commonly, however, they have exceptional amino acid compositions and are predicted to be intrinsically disordered, to undergo phase separation, or have prion-like behavior. Phase separation has recently been shown to play roles in Rho function and bacterial fitness during harsh conditions in one species and this study suggests a more widespread role. In conclusion, diverse atypical Rho factors are broadly distributed among bacteria, suggesting additional cellular roles.
Translation-independent association of mRNAs encoding protomers of the 5-HT2A-mGlu2 receptor complex in living cells
Authors: Saha Somdatta , Gonzalez-Maeso Javier 
Published: June 2024

SUMMARYThe serotonin 2A receptor (5-HT2AR) and the metabotropic glutamate 2 receptor (mGluR2) form heteromeric G protein-coupled receptor (GPCR) complexes through a direct physical interaction. Co-translational association of mRNAs encoding subunits of heteromeric ion channels has been reported, but whether complex assembly of GPCRs occurs during translation remains unknown. Ourin vitrodata reveal evidence of co-translational modulation in5-HT2ARandmGluR2mRNAs following siRNA-mediated knockdown. Interestingly, immunoprecipitation of either 5-HT2AR or mGluR2, using an antibody targeting epitope tags at their N-terminus, results in detection of both transcripts associated with ribonucleoprotein complexes containing RPS24. Additionally, we demonstrate that the mRNA transcripts of5-HT2ARandmGluR2associate autonomously of their respective encoded proteins. Validation of this translation-independent association is extendedex vivousing mouse frontal cortex samples. Together, these findings provide mechanistic insights into the co-translational assembly of GPCR heteromeric complexes, unraveling regulatory processes governing protein-protein interactions and complex formation.
AI-m6ARS: Machine learning-driven m6A RNA methylation site discovery with integrated sequence, conservation, and geographical descriptors
Authors: Uthayopas Korawich , de Sá Alex G. C. , Ascher David B. 
Published: June 2024

ABSTRACTN6-Methyladenosine (m6A) is a predominant type of human RNA methylation, regulating diverse biochemical processes and being associated with the development of several diseases. Despite its significance, an extensive experimental examination across diverse cellular and transcriptome contexts is still lacking due to time and cost constraints. Computational models have been proposed to prioritise potential m6A methylation sites, although having limited predictive performance due to inadequate characterisation and modelling of m6A sites. This work presents AI-m6ARS, a novel model that utilises integrated sequence, conservation, and geographical descriptive features to predict human m6A methylation sites. The model was trained using the Light Gradient Boosting Machine (LightGBM) algorithm, which was coupled with comprehensive feature selection to improve the data quality. AI-m6RS demonstrates strong predictive capabilities, achieving an impressive area under the receiver operating characteristic curve of 0.87 on cross-validation. Consistent results on unseen transcripts in a blind test highlight the AI-m6ARS generalisability. AI-m6ARS also demonstrates comparable performance to state-of-the-art models, but offers two significant benefits: the model interpretability and the availability of a user-friendly web server. The AI-m6ARS web server offers valuable insights into the distribution of m6A sites within the human genome, thereby facilitating progress in medical applications.GRAPHICAL ABSTRACT
Inference of the low-energy constants in
Δ
-full chiral effective field theory including a correlated truncation error
Authors: Svensson Isak , Ekström Andreas , Forssén Christian 
Published: June 2024

We sample the posterior probability distributions of the low-energy constants (LECs) in Δ-full chiral effective field theory (χEFT) up to third order. We use eigenvector continuation for fast and accurate emulation of the likelihood and Hamiltonian Monte Carlo to draw effectively independent samples from the posteriors. Our Bayesian inference is conditioned on the Granada database of neutron-proton (np) cross sections and polarizations. We use priors grounded in χEFT assumptions and a Roy-Steiner analysis of pion-nucleon scattering data. We model correlated EFT truncation errors using a two-feature Gaussian process, and find correlation lengths for np scattering energies and angles in the ranges 45–83 MeV and 24–39 degrees, respectively. These correlations yield a nondiagonal covariance matrix and reduce the number of independent scattering data with factors of 8 and 4 at the second and third chiral orders, respectively. The relatively small difference between the second- and third-order predictions in Δ-full χEFT suppresses the marginal variance of the truncation error and the effects of its correlation structure. Our results are particularly important for analyzing the predictive capabilities in nuclear theory.

Published by the American Physical Society
2024
Museum experience in battlefield tourism: a netnographic approach
Authors: Akgül Onur , Eren Duygu 
Published: June 2024

Purpose
This study aims to analyze the war museum experience by analyzing the comments and feedback provided by visitors on Google and TripAdvisor. This analysis intends to uncover the various aspects of war museum experiences.

Design/methodology/approach
A total of 201 comments, in which visitors explicitly articulated their experiences at the museum, were subjected to analysis. The comments were examined using a netnography analysis. Four dimensions; object experience, cognitive experience, introspective experience and social experience were used to group the analyzed remarks.

Findings
The findings indicate that the majority of the participants' museum experiences at the Canakkale Gallipoli Epic Promotion Center were introspective experiences, that the visitors felt extremely strong emotions as a result of the technological systems used in the museum and that they perceived the museum as being in a combat zone. Additionally, it was noted that the appearance of the artifacts in the museums really impressed the tourists and that the museum had provided them with thorough information about the war.

Research limitations/implications
The limitations of this study are the number of visitors to the museum and the number of reviews written on Google and TripAdvisor about the visit experience. Especially since the majority of the reviews on Google do not include comments and only consist of ratings, the number of comments on the museum experience is limited.

Originality/value
While there exists a range of studies examining the experiences of tourists at historical places, there is a scarcity of research that specifically focuses on analyzing the impacts of these experiences from the visitors' standpoint. Given the absence of any existing study examining the experiences of war museum visitors using the netnographic approach within this particular context, this research is believed to possess originality and is anticipated to address the existing gap in the relevant literature. Furthermore, this work holds significant theoretical and practical ramifications for curators and scholars. To the best of the authors’ knowledge, since this research is the first to comprehensively analyze the experiences of war museum visitors using the netnographic approach and no similar studies have been found in existing literature, the findings of this study are considered original.