bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring research quality in a more inclusive way: Evidence from the UK Research Excellence Framework
Authors: Hengel Erin , Sevilla Almudena , Smith Sarah
Published: April 2024

Evidence suggests that common metrics of research quality—e.g. journal publications and citations—are systematically biased against certain groups. But does relying solely on them to evaluate quality lead to lower diversity in academia? In this paper, we start to answer this question by analysing data from the UK’s nationwide research assessment exercise, the Research Excellence Framework. We find that narrowly focussed output-based measures of departmental research quality do indeed negatively correlate with the diversity of departmental staff, while measures of research impact and of the quality of the research environment correlate positively. An aggregate measure that incorporates all three components is therefore likely to better promote staff diversity compared to more narrowly defined output-focused measures. More generally, our results suggest that comprehensive definitions of research quality may be more effective at promoting diversity in academia compared to narrower measures. We further argue that funding decisions informed by broader measures result in more efficient resource allocations across the higher education sector.
Do sell-side analysts say “buy” while whispering “sell”?
Authors: Hirshleifer David , Shi Yushui , Wu Weili
Published: April 2024

We study here say-buy/whisper-sell behavior wherein analysts issue optimistic recommendations to attract retail investors while providing more accurate information to fund managers in private, sometimes resulting in fund managers selling the recommended stocks. We test whether fund managers return the favor using their votes for analysts in a Chinese “star analyst” competition. Managers are more likely to vote for analysts who exhibit greater “say-buy/whisper-sell” behavior toward these managers. This suggests that analysts reduce the accuracy of their public recommendations, thereby maintaining the value of their private advice to funds. Our findings help explain several empirical puzzles about analyst public recommendations.
Museum Genomics Reveals the Hybrid Origin of an Extinct Crater Lake Endemic
Authors: Tims Amy R , Unmack Peter J , Hammer Michael P , Brown Culum , Adams Mark , McGee Matthew D
Published: April 2024

Crater lake fishes are common evolutionary model systems, with recent studies suggesting a key role for gene flow in promoting rapid adaptation and speciation. However, the study of these young lakes can be complicated by human-mediated extinctions. Museum genomics approaches integrating genetic data from recently extinct species are, therefore, critical to understanding the complex evolutionary histories of these fragile systems. Here, we examine the evolutionary history of an extinct Southern Hemisphere crater lake endemic, the rainbowfish Melanotaenia eachamensis. We undertook a comprehensive sampling of extant rainbowfish populations of the Atherton Tablelands of Australia alongside historical museum material to understand the evolutionary origins of the extinct crater lake population and the dynamics of gene flow across the ecoregion. The extinct crater lake species is genetically distinct from all other nearby populations due to historic introgression between 2 proximate riverine lineages, similar to other prominent crater lake speciation systems, but this historic gene flow has not been sufficient to induce a species flock. Our results suggest that museum genomics approaches can be successfully combined with extant sampling to unravel complex speciation dynamics involving recently extinct species.
Lytic/Lysogenic Transition as a Life-History Switch
Authors: Roughgarden Joan
Published: April 2024

The transition between lytic and lysogenic life cycles is the most important feature of the life-history of temperate viruses. To explain this transition, an optimal life-history model is offered based a discrete-time formulation of phage/bacteria population dynamics that features infection of bacteria by Poisson sampling of virions from the environment. The time step is the viral latency period. In this model, density-dependent viral absorption onto the bacterial surface produces virus/bacteria coexistence and density dependence in bacterial growth is not needed. The formula for the transition between lytic and lysogenic phases is termed the ‘fitness switch’. According to the model, the virus switches from lytic to lysogenic when its population grows faster as prophage than as virions produced by lysis of the infected cells, and conversely for the switch from lysogenic to lytic. A prophage that benefits the bacterium it infects automatically incurs lower fitness upon exiting the bacterial genome, resulting in its becoming locked into the bacterial genome in what is termed here as a ‘prophage lock’. The fitness switch qualitatively predicts the ecogeographic rule that environmental enrichment leads to microbialization with a concomitant increase in lysogeny, fluctuating environmental conditions promote virus-mediated horizontal gene transfer, and prophage-containing bacteria can integrate into the microbiome of a eukaryotic host forming a functionally integrated tripartite holobiont. These predictions accord more with the ‘Piggyback-the-Winner’ hypothesis than with the ‘Kill-the-Winner’ hypothesis in virus ecology.
Disaster Plant Pathology: Smart Solutions for Threats to Global Plant Health from Natural and Human-Driven Disasters
Authors: Etherton Berea A. , Choudhury Robin A. , Alcalá Briseño Ricardo I. , Mouafo-Tchinda Romaric A. , Plex Sulá Aaron I. , Choudhury Manoj , Adhikari Ashish , Lei Si Lin , Kraisitudomsook Nattapol , Buritica Jacobo Robledo , Cerbaro Vinicius A. , Ogero Kwame , Cox Cindy M. , Walsh Stephen P. , Andrade-Piedra Jorge L. , Omondi Bonaventure Aman , Navarrete Israel , McEwan Margaret A. , Garrett Karen A.
Published: April 2024

Disaster plant pathology addresses how natural and human-driven disasters impact plant diseases and the requirements for smart management solutions. Local to global drivers of plant disease change in response to disasters, often creating environments more conducive to plant disease. Most disasters have indirect effects on plant health through factors such as disrupted supply chains and damaged infrastructure. There is also the potential for direct effects from disasters, such as pathogen or vector dispersal due to floods, hurricanes, and human migration driven by war. Pulse stressors such as hurricanes and war require rapid responses, whereas press stressors such as climate change leave more time for management adaptation but may ultimately cause broader challenges. Smart solutions for the effects of disasters can be deployed through digital agriculture and decision support systems supporting disaster preparedness and optimized humanitarian aid across scales. Here, we use the disaster plant pathology framework to synthesize the effects of disasters in plant pathology and outline solutions to maintain food security and plant health in catastrophic scenarios. We recommend actions for improving food security before and following disasters, including (i) strengthening regional and global cooperation, (ii) capacity building for rapid implementation of new technologies, (iii) effective clean seed systems that can act quickly to replace seed lost in disasters, (iv) resilient biosecurity infrastructure and risk assessment ready for rapid implementation, and (v) decision support systems that can adapt rapidly to unexpected scenarios.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Merit-Based Incentive Payment System: How Are Plastic Surgeons Performing?
Authors: Perez Otero Sofia , Diaz Allison L. , Hemal Kshipra , Boyd Carter J. , Lee Wen-Yu , Karp Nolan S.
Published: April 2024

Background:

The Merit-based Incentive Payment System (MIPS) is a payment model implemented to promote high-value care through performance-based adjustments of Medicare reimbursements. Higher scores indicate superior performance in health care quality, efficiency, and interoperability, which can result in financial advantages. Given the paucity of literature, the authors aimed to characterize plastic surgery performance in MIPS.

Methods:

The Centers for Medicare and Medicaid Services online data repository was queried for data on MIPS performance of plastic surgeons from 2019 to 2021. Descriptive analyses and multivariable logistic regression were conducted to identify predictors of receiving bonus payment for exceptional performance.

Results:

Approximately 1400 surgeons were sampled in each year. The median number of Medicare beneficiaries and percentage of dually eligible beneficiaries—eligible for Medicare and Medicaid—were higher in 2019 (P < 0.001). Beneficiary median hierarchical condition category risk score, which measures expected health care costs and needs based on health status, was lower in 2021 (P < 0.001). The most common reporting schema was reporting as a group. Total MIPS score increased from 2019 to 2020 to 2021 (90.2 versus 96.4 versus 98.3, respectively; P < 0.001), but quality score progressively decreased (98.8 versus 95.5 versus 89.90, respectively; P < 0.001). Fewer physicians received positive adjustment and bonus payments in 2020 and 2021. Predictors of receiving bonus payments were reporting as an alternative payment model, practice size greater than 24, and having 10% to 49% of dually eligible beneficiaries (P < 0.05).

Conclusion:

Understanding performance of plastic surgeons in MIPS can guide future policy direction and ensure that high-quality care translates into improved patient outcomes across all fields and levels of social vulnerability.
Orthognathic Considerations of Maxillary and Mandibular Asymmetry at Skeletal Maturity in Patients with Cleft Lip and Palate
Authors: Salinero Lauren K , Friedman Leigh , Shulkin Jared M , Barrero Carlos E , Wagner Connor S , Pontell Matthew E , Swanson Jordan W , Bartlett Scott P , Nah Hyun-Duck , Taylor Jesse A
Published: April 2024

Background:

Improving occlusion and aesthetics is the primary objective of orthognathic surgery for patients with cleft lip and palate (CLP). However, these patients often suffer from horizontal, vertical, and rotational asymmetry in addition to maxillary retrusion. This study aims to describe maxillary and mandibular asymmetry in patients with CLP undergoing orthognathic surgery and analyze its anatomic basis.

Methods:

Patients with isolated CLP undergoing CT imaging prior to orthognathic surgery were retrospectively reviewed. Maxillary and mandibular positioning and dimensional symmetry were evaluated. Incidence of clinically significant asymmetry, correlations between areas of asymmetry, and associations with clinical history were analyzed.

Results:

Fifty-eight patients, with mean age 17 years were analyzed, including 32 patients with unilateral CLP and 26 with bilateral CLP. Twenty (34%) patients demonstrated chin deviation ≥4mm and 21 (36%) had a ≥5% discrepancy in mandibular ramus lengths. Horizontal occlusal plane cant of ≥2° was seen in 20 (34%) maxillae and 28 (48%) mandibles, with dental arch yaw ≥2° noted in 32 (55%) of both maxillae and mandibles. Chin deviation correlated with maxillary cant, discrepancy in ramus length, discrepancy in mandibular body length, and discrepancy in condylar volume (p<0.05). Bilateral and unilateral CLP did not show significantly different asymmetry on any measure (p>0.05).

Conclusions:

Both maxillary and mandibular asymmetry is common in skeletally mature patients with CLP and frequently results in notable chin deviation. Preoperative three-dimensional imaging and virtual surgical planning of orthognathic surgery aid in recognition of facial asymmetries and reveal opportunities to optimize results in this population.
Bumblebee nest departures under low light conditions at sunrise and sunset
Authors: Chapman Katherine E. , Smith Michael T. , Gaston Kevin J. , Hempel de Ibarra Natalie
Published: April 2024

Only a few diurnal animals, such as bumblebees, extend their activity into the time around sunrise and sunset when illumination levels are low. Low light impairs viewing conditions and increases sensory costs, but whether diurnal insects use low light as a cue to make behavioural decisions is uncertain. To investigate how they decide to initiate foraging at these times of day, we observed bumblebee nest-departure behaviours inside a flight net, under naturally changing light conditions. In brighter light bees did not attempt to return to the nest and departed with minimal delay, as expected. In low light the probability of non-departures increased, as a small number of bees attempted to return after spending time on the departure platform. Additionally, in lower illumination bees spent more time on the platform before flying away, up to 68 s. Our results suggest that bees may assess light conditions once outside the colony to inform the decision to depart. These findings give novel insights into how behavioural decisions are made at the start and the end of a foraging day in diurnal animals when the limits of their vision impose additional costs on foraging efficiency.
Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field
Authors: Ramezanpour H. , Kehoe D. H. , Schall J. D. , Fallah M.
Published: April 2024

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field (FEF) of two rhesus monkeys shifting gaze to a target while an isoeccentric distractor appeared either left or right of the target at various delays after target presentation. We found that the population level of pre-saccadic activity encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature towards the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved towards distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push-pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets.

Significant Statement

This study not only advances our understanding of oculomotor function in dynamic environments but also has potential clinical relevance for diagnosing and understanding disorders characterized by abnormal saccade trajectories. Our research elucidates the neural mechanisms behind saccade trajectories that are not always linear due to the brain’s integration of multiple visual cues and/or motor plans. By analyzing the frontal eye field (FEF) activity in rhesus monkeys, we found that saccade directionality and timing are influenced by the interaction between FEF visual neurons representing target and distractor stimuli. The FEF’s role extends beyond a winner-takes-all approach, incorporating saccade vector averaging computations that produce curved saccades. Furthermore, ipsilateral visual neurons encode distractor suppression that drives curvature away from the distractor.
Retrotransposon expression is upregulated by aging and suppressed during regeneration of the limb in the axolotl (Ambystoma mexicanum)
Authors: Ruiz-Pérez Samuel , Torres-Arciga Karla , Sámano-Salazar Cynthia Gabriela , Ocampo-Cervantes José Antonio , Cervera Alejandra , Castro-Hernández Clementina , Soto-Reyes Ernesto , Alcaraz Nicolas , González-Barrios Rodrigo
Published: April 2024

The axolotl (Ambystoma mexicanum) has a great capacity to regenerate its tissues and whole-body parts; however, the fidelity and success of its regenerative process diminish with age. Retrotransposons make up the largest portion of the axolotl genome, and their expression may be involved in this age-related decline. Through an integrative analysis of repetitive element expression using RNA-seq, we show that Ty3 retrotransposons are highly upregulated in the axolotl as an effect of chronological aging. Other non-LTR transposons, including LINE-1, function as hubs of gene coexpression networks involved in muscle development, N-methyltransferase activity, amyloid proteolysis, and regulation of apoptosis and connective tissue replacement, which are also suppressed by the increase in age. In contrast, we find that during regeneration of the limb these pathways and the expression of Ty3 retrotransposons are distinctly downregulated. Although the blastema is able to readjust most of the transposon dysregulation caused by aging, there are still several elements that remain affected and may have an impact in the metabolic and immune responses during the regenerative process. We also report that numerous C2H2-ZFPs, especially KRAB-ZPFs, are coexpressed with hub retrotransposons, which reveals their potential as important regulators of transposable element expression during aging and regeneration. This integrative analysis provides a comprehensive profile of retrotransposon expression through chronological aging and during limb regeneration in the axolotl and indicates that transposable elements are responsive to physiological changes in a tissue-specific way and participate in the gene co-regulatory networks underlying the regenerative process.

Graphical abstract.

Transcriptomic analyses of adult and sub-adult axolotls offer an insight into the potential role of retrotransposons during limb regeneration and how they are affected by chronological aging. Retrotransposons of the Ty3 superfamily are usually suppressed during regeneration, but after experiencing a significant upregulation through the aging of the axolotl, their regulation during tissue repair is limited. It has been reported that the success of the axolotl’s regenerative process diminishes with age. Our findings show that Ty3 and other transposon families, such as LINE-1, are involved in the gene regulatory networks that suppress muscle development, apoptosis control, and tissue replacement due to aging. These results suggest that repetitive element expression may indirectly constrain the regenerative capacities of older axolotls.
WENDY: Covariance Dynamics Based Gene Regulatory Network Inference
Authors: Wang Yue , Zheng Peng , Cheng Yu-Chen , Wang Zikun , Aravkin Aleksandr
Published: April 2024

Determining gene regulatory network (GRN) structure is a central problem in biology, with a variety of inference methods available for different types of data. For a widely prevalent and challenging use case, namely single-cell gene expression data measured after intervention at multiple time points with unknown joint distributions, there is only one known specifically developed method, which does not fully utilize the rich information contained in this data type. We develop an inference method for the GRN in this case, netWork infErence by covariaNce DYnamics, dubbed WENDY. The core idea of WENDY is to model the dynamics of the covariance matrix, and solve this dynamics as an optimization problem to determine the regulatory relationships. To evaluate its effectiveness, we compare WENDY with other inference methods using synthetic data and experimental data. Our results demonstrate that WENDY performs well across different data sets.
Leveraging a Comprehensive Unbiased RNAseq Database Uncovers New Human Monocyte-Derived Macrophage Subtypes Within Commonly Employed In Vitro Polarization Methods
Authors: Smyth Timothy , Payton Alexis , Hickman Elise , Rager Julia E , Jaspers Ilona
Published: April 2024

Macrophages are pivotal innate immune cells which exhibit high phenotypic plasticity and can exist in different polarization states dependent on exposure to external stimuli. Numerous methods have been employed to simulate macrophage polarization states to test their function in vitro. However, limited research has explored whether these polarization methods yield comparable populations beyond key gene, cytokine, and cell surface marker expression. Here, we employ an unbiased comprehensive analysis using data organized through the all RNA-seq and ChIP-seq sample and signature search (ARCHS4) database, which compiles all RNAseq data deposited into the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). In silico analyses were carried out demonstrating that commonly employed macrophage polarization methods generate distinct macrophage subsets that remained undescribed until now. Our analyses confirm existing knowledge on macrophage polarization, while revealing nuanced differences between M2a and M2c subpopulations, suggesting non-interchangeable stimuli for M2a polarization. Furthermore, we identify divergent gene expression patterns in M1 macrophages following standard polarization protocols, indicating significant subset distinctions. Consequently, equivalence cannot be assumed among polarization regimens for in vitro macrophage studies, particularly in simulating diverse pathogen responses.
The Rac1 homolog CED-10 is a component of the MES-1/SRC-1 pathway for asymmetric division of theC. elegansEMS blastomere
Authors: Lamb Helen , Liro Małgorzata , Myles Krista , Fernholz McKenzi , Anderson Holly , Rose Lesilee S.
Published: April 2024

Asymmetric cell division is essential for the creation of cell types with different identities and functions. The EMS blastomere of the four-cellCaenorhabditis elegansembryo undergoes an asymmetric division in response to partially redundant signaling pathways. One pathway involves a Wnt signal emanating from the neighboring P2 cell, while the other pathway is defined by the receptor-like MES-1 protein localized at the EMS/P2 cell contact, and the cytoplasmic kinase SRC-1. In response to these pathways, the EMS nuclear-centrosome complex rotates so that the spindle forms on the anterior-posterior axis; after division, the daughter cell contacting P2 becomes the endodermal precursor cell. Here we identify the Rac1 homolog, CED-10, as a new component of the MES-1/SRC-1 pathway. Loss of CED-10 affects both spindle positioning and endoderm specification. Although MES-1 is still present at the EMS/P2 contact inced-10embryos, SRC-1 dependent phosphorylation is reduced. These and other results suggest that CED-10 acts downstream of MES-1 and upstream of, or at the level of, SRC-1 activity. In addition, we find that the branched actin regulator ARX-2 is enriched at the EMS/P2 cell contact site, in a CED-10 dependent manner. Loss of ARX-2 results in spindle positioning defects, suggesting that CED-10 acts through branched actin to promote the asymmetric division of the EMS cell.
Parallel Labeled-Line Organization of Sympathetic Outflow for Selective Organ Regulation in Mice
Authors: Harima Yukiko , Tsurutani Masafumi , Uchida Shuntaro , Inada Kengo , Hagihara Mitsue , Irie Satsuki , Shigeta Mayo , Abe Takaya , U. Inoue Yukiko , Inoue Takayoshi , Miyamichi Kazunari
Published: April 2024

The sympathetic nervous system is vital in maintaining homeostasis and responding to environmental changes1–3. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), which influence various organs both through neuronal pathways via postganglionic neurons and through endocrine processes by innervating the adrenal gland. Despite decades of research supporting the concept of selective control within this system1,4–9, the neural circuit organization responsible for the specificity of sympathetic outflow remains poorly understood. Notably, classical anatomical studies in rats have not revealed a definitive molecular code governing SPNs, nor have they confirmed the existence of SPNs strictly corresponding to specific output targets1,6,10,11. To reconcile this discrepancy, we aim to integrate recent transcriptome data of SPNs12,13in mice with viral-genetic toolkits14to map axonal projections and manipulate the functions of SPNs governing the gastrointestinal tract and adrenal gland. Here, we have identified two subtypes of SPNs in the lower thoracic spinal cord, defined at the molecular level, exhibiting non-overlapping patterns of innervation. Chemogenetic manipulations on these distinct SPN subtypes revealed selective impacts on the digestive functions in the gastrointestinal tracts or glucose metabolism mediated by the adrenal gland, respectively. This molecularly delineated parallel labeled-line organization in sympathetic outflows presents a potential avenue for selectively manipulating organ functions.
STARDUST: a pipeline for the unbiased analysis of astrocyte regional calcium dynamics
Authors: Wu Yifan , Dai Yanchao , Lefton Katheryn B. , Holy Timothy E. , Papouin Thomas
Published: April 2024

Calcium imaging has become a popular way to probe astrocyte activity, but few analysis methods holistically capture discrete calcium signals that occur across the astrocyte domain. Here, we introduce STARDUST, a pipeline for the Spatio-Temporal Analysis of Regional Dynamics & Unbiased Sorting of Transients from fluorescence recordings of astrocytes, and provide step-by-step guidelines. STARDUST yields fluorescence time- series from data-defined regions of activity and performs systematic signal detection and feature extraction, enabling the in-depth and unbiased study of astrocyte calcium signals.

Graphical abstract
Multi-ancestry Whole-exome Sequencing Study of Alcohol Use Disorder in Two Cohorts
Authors: Wang Lu , Kranzler Henry R. , Gelernter Joel , Zhou Hang
Published: April 2024

Alcohol use disorder (AUD) is a leading cause of death and disability worldwide. There has been substantial progress in identifying genetic variants underlying AUD. However, there are few whole-exome sequencing (WES) studies of AUD. We analyzed WES of 4,530 samples from the Yale-Penn cohort and 469,835 samples from the UK Biobank (UKB). After quality control, 1,420 AUD cases and 619 controls of European ancestry (EUR) and 1,142 cases and 608 controls of African ancestry (AFR) from Yale-Penn were retained for subsequent analyses. WES data from 415,617 EUR samples (12,861 cases), 6,142 AFR samples (130 cases) and 4,607 South Asian (SAS) samples (130 cases) from UKB were also analyzed. Single-variant association analysis identified the well-known functional variant rs1229984 inADH1B(P=4.88×10-31) and several other common variants inADH1C. Gene-based tests identifiedADH1B(P=1.00×10-31),ADH1C(P=5.23×10-7),CNST(P=1.19×10-6), andIFIT5(3.74×10-6). This study extends our understanding of the genetic basis of AUD.
Otolith shape variability of labrid fish from Rapa Nui (Easter Island), southeastern Pacific
Authors: Castro-García Andrés , Delrieu-Trottin Erwan , Saenz-Agudelo Pablo , Rapu-Edmunds Cristian , Plaza Guido , Márquez Federico , Landaeta Mauricio F.
Published: April 2024

Fish otolith shape provides valuable insights into the taxonomic, phylogenetic, and ecological traits of fish species. This study aimed to assess and compare the phenotypic variation in otolith shape among four labrid species (Anampses femininus, Coris debueni, Pseudolabrus fuentesiandThalassoma lutescens) inhabiting Rapa Nui (Easter Island) in the southeastern Pacific Ocean, utilizing geometric morphometrics and aging methods. Age estimation based on otolith structure indicated that collected specimens were adults, ranging between 1 and 3 years old. Allometric analysis revealed low but significant variation (5.40%), primarily driven by changes in otolith width, resulting in distinct morphologies. Principal Component Analysis (PCA) of sagittal otoliths elucidated significant morphospace variation among species, with the first two PCs explaining 60.3% of the total variance. PC1 distinguished between elongated sagittal shapes (e.g.,P. fuentesi) and robust sagittae (e.g.,T. lutescens), while PC2 correlated with otolith roundness, delineating variations within species. Canonical variate analysis further highlighted differences in otolith shape, with significant variations detected among all species. The Discriminant function analysis showed high levels of discrimination accuracy for most of species’ pairs. Except forC. debueni-P. fuentesi(89%) andC. debueni-T. lutescens(96%), all other species pairs achieved 100% discrimination, highlighting the reliability of otolith shape as a distinguishing characteristic for the studied species. Overall, our findings emphasize the value of otolith shape analysis for characterizing and distinguishing Rapa Nui labrid species. This offers potential applications such as identifying prey within the digestive systems of large fish or bird predators in the vicinity of this isolated island in the South Pacific Ocean or archaeofauna studies.
The persistence of memory: prior memory responses modulate behavior and brain state engagement
Authors: Wheelock Justin R. , Long Nicole M.
Published: April 2024

Memory brain states may influence how we experience an event. Memory encoding and retrieval constitute neurally dissociable brain states that individuals can selectively engage based on top-down goals. To the extent that memory states linger in time – as suggested by prior behavioral work – memory states may influence not only the current experience, but also subsequent stimuli and judgments. Thus lingering memory states may have broad influences on cognition, yet this account has not been directly tested utilizing neural measures of memory states. Here we address this gap by testing the hypothesis that memory brain states are modulated by memory judgments, and that these brain states persist for several hundred milliseconds. We recorded scalp electroencephalography (EEG) while participants completed a recognition memory task. We used an independently validated multivariate mnemonic state classifier to assess memory state engagement. We replicate prior behavioral findings; however, our neural findings run counter to the predictions made on the basis of the behavioral data. Surprisingly, we find that prior responses modulate current memory state engagement on the basis of response congruency. That is, we find strong engagement of the retrieval state on incongruent trials – when a target is preceded by a correct rejection of a lure and when a lure is preceded by successful recognition of a target. These findings indicate that cortical brain states are influenced by prior judgments and suggest that a non-mnemonic, internal attention state may be recruited to in the face of changing demands in a dynamic environment.
Multimodal mechano-microscopy reveals mechanical phenotypes of breast cancer spheroids in three dimensions
Authors: Mowla Alireza , Hepburn Matt S. , Li Jiayue , Vahala Danielle , Amos Sebastian E. , Hirvonen Liisa M. , Sanderson Rowan W. , Wijesinghe Philip , Maher Samuel , Choi Yu Suk , Kennedy Brendan F.
Published: April 2024

Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TME). While the shortcomings of two-dimensional (2D) models in replicatingin situcell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiologyin situ.
Genetic-based inference of densities, effective and census sizes of expanding riverine meta-populations of an invasive large-bodied freshwater fish (Silurus glanis L.)
Authors: Paz-Vinas Ivan , Loot Géraldine , Boulêtreau Stéphanie , Chiarello Marlène , Veyssière Charlotte , Ferriol Jessica , Santoul Frédéric
Published: April 2024

Effective (Ne) and census (Nc) population sizes are key eco-evolutionary parameters. Jointly estimating them have an important practical value for efficient conservation and wildlife monitoring and management. Assessing Neand Ncremains however challenging for elusive, rare species or species inhabiting in complex habitats like large rivers. Genetic-based Neestimations could help resolve complex situations, as only a handful of genotyped individuals are needed to estimate Ne, and then NCcan be subsequently using an Ne/NCratio. However, most Neestimation methods are based on restrictive assumptions (e.g. Wright-Fisher model) making them inappropriate for inferring Neand Ncfor populations and species exhibiting complex dynamics. Here, we aimed at estimating Ne, NCand densities for meta-populations of a large invasive freshwater fish (the European catfishSilurus glanis) that has been introduced in the Garonne-Dordogne river basin (Southwestern France), using a framework that combines multiple data sources and approaches. First, we characterized spatial patterns of genetic variation using microsatellite genotype data, revealing a significant isolation by distance pattern informing about the species’ dispersal capacities. We then detected four genetically-distinct clusters of individuals coexisting in the river basin that might be the result of multiple introductions from different genetic sources. Further, we characterized the demographic expansion of the species at the river basin scale by analyzing data from a multidecadal demographic monitoring survey, and estimated a specific Ne/Nc ratio for this species. We finally combined all the gathered information to design four competing demo-genetic models accounting for all the complexity ofS. glanismeta-populations inhabiting the river basin. We simulated data under these models and then inferred Ne, Nc and densities through approximate Bayesian computation and random forest procedures. We show how multiple genetic and non-genetic approaches can be combined to estimate Neand Ncin hard-to-monitor meta-populations exhibiting complex demo-evolutionary dynamics.
Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2
Authors: Como Christina N. , O’Rourke Rebecca , Winkler Caitlin , Mitchell Danae , Tran Luuli , Lorberbaum David , Sussel Lori , Franco Santos , Siegenthaler Julie
Published: April 2024

The meninges act as a regulator of brain development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meningeal-derived retinoic acid (RA) promotes neocortical neural progenitor cell cycle exit; however, the underlying molecular mechanism is unknown. Here, we used spatial transcriptomics and profiling of retinoic-acid receptor-α (RARα) DNA binding inFoxc1-mutant embryos that lack meninges-derived ligands to identify the neurogenic transcriptional mechanisms of RA signaling in telencephalic neural progenitors. We determined that meningeal-derived RA controls neurogenesis by suppressing progenitor self-renewal pathways Notch signaling and the transcription factor Sox2. We show that RARα binds in theSox2otpromoter, a long non-coding RNA that regulatesSox2expression, and RA promotesSox2otexpression in neocortical progenitors. Our findings elucidate a previously unknown mechanism of how meningeal RA coordinates neocortical development and insight into how defects in meningeal development may cause neurodevelopmental disorders.
Does Ethnicity Alters the Risk of Stroke in Patients with Modifiable Cardiometabolic Risk Factors?
Authors: Delord Marc , Ashworth Mark , Douiri Abdel
Published: April 2024

Background

Ethnic inequality in stroke risk was partially explained by history of hypertension, diabetes, and socioeconomic status. We aimed to estimate the impact of ethnicity on stroke risk in patients with hypertension, diabetes or hypercholesterolaemia.

Methods

Multistate models were constructed using electronic health records including date at onset of stroke, stroke risk factors, and the Index of Multiple Deprivation in adult patients of Asian, Black, or White ethnicity, registered in 41 general practices in south London between 2005 and 2021. Transitions to hypertension, diabetes, or hypercholesterolaemia (transition 1) and from these risk factors to stroke (transitions 2) were considered.

Results

Of the 849,968 registered patients, 651,888 (76·7%) were of Asian (8·6%), Black (18·2%), or White (73·2%) ethnicity and 54·1% were female. Patients of Black ethnicity had higher incidence of stroke (2·1%) and cardiometabolic risk factors, whereas patients of Asian and White ethnicity had intermediate and lower levels of stroke (1·2% and 1·0% respectively) and cardiometabolic risk factors. Asian and Black ethnicities were associated with higher risks in transition 1 compared to White ethnicity. Ethnicity did not alter transition 2, except for hypercholesterolaemia, Black ethnicity being associated with higher risk of stroke compared to Asian and White ethnicity.

Conclusion

Our results confirm that Black ethnicity does not confer excess stroke risk in patients with hypertension or diabetes. This observation was also made for Asian ethnicity. Black ethnicity was associated with increased stroke risk only in patients with Hypercholesterolaemia.

Funding

Guys and St Thomas grant (EIC180702).
A collicular map for touch-guided tongue control
Authors: Ito Brendan S. , Gao Yongjie , Kardon Brian , Goldberg Jesse H.
Published: April 2024

Accurate goal-directed behavior requires the sense of touch to be integrated with information about body position and ongoing motion1,2,3. Behaviors like chewing, swallowing and speech critically depend on precise tactile events on a rapidly moving tongue4,5, but neural circuits for dynamic touch-guided tongue control are unknown. Using high speed videography, we examined 3D lingual kinematics as mice drank from a water spout that unexpectedly changed position during licking, requiring re-aiming in response to subtle contact events on the left, center or right surface of the tongue. Mice integrated information about both precise touch events and tongue position to re-aim ensuing licks. Surprisingly, touch-guided re-aiming was unaffected by photoinactivation of tongue sensory, premotor and motor cortices, but was impaired by photoinactivation of the lateral superior colliculus (latSC). Electrophysiological recordings identified latSC neurons with mechanosensory receptive fields for precise touch events that were anchored in tongue-centered, head-centered or conjunctive reference frames. Notably, latSC neurons also encoded tongue position before contact, information important for tongue-to-head based coordinate transformations underlying accurate touch-guided aiming. Viral tracing revealed tongue sensory inputs to the latSC from the lingual trigeminal nucleus, and optical microstimulation in the latSC revealed a topographic map for aiming licks. These findings demonstrate for the first time that touch-guided tongue control relies on a collicular mechanosensorimotor map, analogous to collicular visuomotor maps associated with visually-guided orienting across many species.
RNA processing by the CRISPR-associated NYN ribonuclease
Authors: Chi Haotian , White Malcolm F
Published: April 2024

CRISPR-Cas systems confer adaptive immunity in prokaryotes, facilitating the recognition and destruction of invasive nucleic acids. Type III CRISPR systems comprise large, multisubunit ribonucleoprotein complexes with a catalytic Cas10 subunit. When activated by the detection of foreign RNA, Cas10 generates nucleotide signalling molecules that elicit an immune response by activating ancillary effector proteins. Among these systems, theBacteroides fragilistype III CRISPR system was recently shown to produce a novel signal molecule, SAM-AMP, by conjugating ATP and SAM. SAM-AMP regulates a membrane effector of the CorA family to provide immunity. Here, we focus on NYN, a ribonuclease encoded within this system, probing its potential involvement in crRNA maturation. Structural modelling andin vitroribonuclease assays reveal that NYN displays robust sequence-nonspecific, Mn2+-dependent ssRNA-cleavage activity. Our findings suggest a role for NYN in trimming crRNA intermediates into mature crRNAs, which is necessary for type III CRISPR antiviral defence. This study sheds light on the functional relevance of CRISPR-associated NYN proteins and highlights the complexity of CRISPR-mediated defence strategies in bacteria.
Chemical tools to define and manipulate interferon-inducible Ubl protease USP18
Authors: Davis Griffin J. , Omole Anthony O. , Jung Yejin , Rut Wioletta , Holewinski Ronald , Suazo Kiall F. , Kim Hong-Rae , Yang Mo , Andresson Thorkell , Drag Marcin , Yoo Euna
Published: April 2024

Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating interferon-inducible ubiquitin-like (Ubl) modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) capable of selectively detecting USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) by incorporating unnatural amino acids into the C-terminal tail of ISG15. Combining with a ubiquitin-based DUB ABP, the selective USP18 ABP is employed in a chemoproteomic screening platform to identify and assess inhibitors of DUBs including USP18. We further demonstrate that USP18 ABPs can be utilized to profile differential activities of USP18 in lung cancer cell lines, providing a strategy that will help define the activity-related landscape of USP18 in different disease states and unravel important (de)ISGylation-dependent biological processes.
Intact and Degenerate Diguanylate Cyclases regulateShigellaCyclic di-GMP
Authors: Ojha Ruchi , Krug Stefanie , Jones Prentiss , Koestler Benjamin J.
Published: April 2024

The intracellular human pathogenShigellainvades the colonic epithelium to cause disease. Prior to invasion, this bacterium navigates through different environments within the human body, including the stomach and the small intestine. To adapt to changing environments,Shigellauses the bacterial second messenger c-di-GMP signaling system, synthesized by diguanylate cyclases (DGCs) encoding GGDEF domains.Shigella flexneriencodes a total of 9 GGDEF or GGDEF-EAL domain enzymes in its genome, but 5 of these genes have acquired mutations that presumably inactivated the c-di-GMP synthesis activity of these enzymes. In this study, we examined individualS. flexneriDGCs for their role in c-di-GMP synthesis and pathogenesis. We individually expressed each of the 4 intact DGCs in anS. flexneristrain where these 4 DGCs had been deleted (Δ4DGC). We found that the 4S. flexneriintact DGCs synthesize c-di-GMP at different levelsin vitroand during infection of tissue-cultured cells. We also found thatdgcFanddgcIexpression significantly reduces invasion and plaque formation, anddgcFexpression increases acid sensitivity, and that these phenotypes did not correspond with measured c-di-GMP levels. However, deletion of these 4 DGCs did not eliminateS. flexneric-di-GMP, and we found thatdgcE, dgcQ,anddgcN, which all have nonsense mutations prior to the GGDEF domain, still produce c-di-GMP. TheseS. flexneridegenerate DGC genes are expressed as multiple proteins, consistent with multiple start codons within the gene. We propose that both intact and degenerate DGCs contribute toS. flexneric-di-GMP signaling.
Neural and behavioral similarity-driven tuning curves for manipulable objects
Authors: Valério D. , Peres A. , Bergström F. , Seidel P. , Almeida J.
Published: April 2024

In our daily activities, we encounter numerous objects that we successfully distinguish and recognize within a fraction of a second. This holds for coarse distinctions (e.g., cat vs. hammer) but also for more challenging within-category distinctions that require fine-grain analysis (e.g., cat vs. dog). The efficiency of this recognition depends on how the brain organizes object-related information. While several attempts have focused on unravelling large-scale organization principles, research on within-category organization of knowledge is rather limited. Here, we explored the fine-grain organization of object knowledge and investigated whether manipulable objects are organized and represented in terms of their similarity. To accomplish this, different groups of individuals participated in a behavioral and fMRI release from adaptation experiment. Adaptation was induced by presenting different exemplars of a particular object, and release from adaptation was elicited by the presentation of a deviant object. The relationship between adaptation and deviant objects was manipulated into four levels of similarity, measured by feature overlap between these objects. Our findings revealed that increasing object similarity provoked progressively slower reaction times and progressively weaker fMRI release from adaptation. Specifically, we identified similarity-driven tuning curves for the release from adaptation in the medial fusiform, collateral sulcus, parahippocampal gyri, lingual gyri, lateral occipital complex, and occipito-parietal cortex. These results suggest that the processing and representation of objects in the brain and our ability to perform fine discriminations between objects reflect real-world object similarity in a relatively parametric manner.
Multipartite continuous-variable optical quantum entanglement: Generation and application
Authors: Asavanant Warit , Furusawa Akira
Published: April 2024

Quantum entanglement is a fundamental resource for various quantum applications and generation of large-scale entanglement is a key quantum technology. In recent years, continuous-variable optical systems have shown promising results in this direction, thanks to deterministic generation and multiplexing via rich degrees of freedom naturally occurring in the optical system. In this paper, we review the generation and applications of multipartite optical quantum entanglement. We begin with a theoretical overview of how to represent and verify multimode continuous-variable quantum states and entanglement. Then, we discuss the multiplexing technique in time, frequency, and spatial domains, and their applications in generation of large-scale entangled states. Afterward, we review the current status and development of the basic technology used in the generation of multipartite quantum entanglement. Finally, we discuss the applications of large-scale quantum entanglement and possible future perspectives.

Published by the American Physical Society
2024