bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marine protected areas promote resilience of kelp forests to marine heatwaves by preserving trophic cascades
Authors: Kumagai Joy A. , Goodman Maurice C. , Villaseñor-Derbez Juan Carlos , Schoeman David S. , Cavanuagh Kyle C. , Bell Tom W. , Micheli Fiorenza , De Leo Giulio , Arafeh-Dalmau Nur 
Published: April 2024

AbstractUnder accelerating threats from climate change impacts, marine protected areas (MPAs) have been proposed as climate adaptation tools to enhance the resilience of marine ecosystems. Yet, debate persists as to whether and how MPAs may promote resilience to climate shocks. Here, we empirically assess whether a network of 85 temperate MPAs in coastal waters promotes resilience against marine heatwaves in Central and Southern California. We use 38 years of satellite-derived kelp cover to test whether MPAs enhance the resistance of kelp forest ecosystems to, and recovery from, the unprecedented 2014–2016 marine heatwave regime. We also leverage a 20-year time series of subtidal community surveys to understand whether protection and recovery of sea urchin predators within MPAs explain emergent patterns in kelp forest resilience through trophic cascades. We find that fully protected MPAs (i.e. no-take marine reserves) significantly enhance the resistance to and recovery of kelp forests to marine heatwaves in Southern California, but not in Central California. Differences in regional responses to the heatwaves may be partly explained by three-level trophic interactions comprising kelp, urchins, and predators of urchins. Urchin abundances in Southern California MPAs are significantly lower within fully protected MPAs during and after the heatwave, while the abundance of their predators are higher. In Central California, there is no significant difference in urchin abundances within protected areas as the current urchin predator, sea otters, are unilaterally protected. Therefore, we provide evidence that fully protected MPAs can be effective climate adaptation tools, but their ability to enhance resilience to extreme climate events depends upon region-specific environmental and ecological dynamics. As nations progress to protect 30% of the oceans by 2030 scientists and managers should consider whether protection will increase resilience to climate-change impacts given their local ecological contexts, and what additional measures may be needed.
Large scale analysis of predicted protein structures links model features toin vivobehaviour
Authors: Stam Michael J. , Oyarzún Diego A. , Laohakunakorn Nadanai , Wood Christopher W. 
Published: April 2024

AbstractRapid advancements in protein structure prediction methods have ushered in a new era of abundant and accurate structural data, providing opportunities to analyse proteins at a scale that has not been possible before. Here we show that features derived solely from predicted structures can be used to understandin vivoprotein behaviour using data-driven methods. We found that these features were predictive ofin vivoprotein production for a set of designed antibodies, enabling identification of high-quality designs. Following on from this result, we calculated these features for a diverse set of ≈500,000 predicted structures, and our analysis showed systematic variation between proteins from different organisms to such an extent that the tree of life could be recapitulated from these data. Given the high degree of functional constraint around the chemistry of proteins, this result is surprising, and could have important implications for the design and engineering of novel proteins.
MicroRNA-27a-5p downregulates the expression of proinflammatory cytokines in lipopolysaccharide-stimulated human dental pulp cells via NF-κB signaling pathway
Authors: Wang Shihan , Kawashima Nobuyuki , Han Peifeng , Sunada-Nara Keisuke , Yu Ziniu , Tazawa Kento , Fujii Mayuko , Kieu Thoai Quoc , Okiji Takashi 
Published: April 2024

AbstractAimTo investigate the effect of microRNA-27a-5p (miR-27a-5p) on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS).MethodologyExpression of miR-27a-5p was evaluated in LPS-stimulated hDPCs isolated from third molars of healthy patients by a TaqMan microRNA assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and a cytometric bead array were used to measure mRNA and protein expression levels, respectively, of proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemotactic protein 1 (MCP1). Luciferase assays and western blotting were conducted to assess nuclear factor κB (NF-κB) activity. Gene/protein expression of NF-κB signaling activators, i.e., transforming growth factor beta-activated kinase 1 binding protein 1 (TAB1), IL-1 receptor-associated kinase 4 (IRAK4), NF-κB p65 (RELA), and follistatin-like 1 (FSTL1), was evaluated by RT-qPCR and western blotting. Transfection of an miR-27a-5p mimic was performed using Lipofectamine RNAiMax reagent. Wildtype and mutated 3□-untranslated region (UTR) of TAB1-contained luciferase reporter vectors were co-transfected with the miR-27a-5p mimic. Small interfering RNA against TAB1 (siTAB1) was designed to block its expression. One-way analysis of variance and Student’st-test were used to determine statistical significance (α = .05).ResultsLPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-κB inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated expression of proinflammatory cytokines, NF-κB activity, and expression of NF-κB signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3□-UTR of TAB1. siTAB1 downregulated NF-κB activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-κB activity, and NF-κB signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimicex vivo.ConclusionsMiR-27a-5p, whose expression was induced by NF-κB signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-κB signaling. In particular, TAB1, a potent NF-κB activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-κB signaling pathway, on pulp inflammation.
Juvenile agile frogs spatially avoid ranavirus-infected conspecifics, but do not show generalized social distancing or self-isolation
Authors: Herczeg Dávid , Horváth Gergely , Bókony Veronika , Herczeg Gábor , Kásler Andrea , Holly Dóra , Mikó Zsanett , Ujhegyi Nikolett , Ujszegi János , Papp Tibor , Hettyey Attila 
Published: April 2024

ABSTRACTExposure to contagious pathogens can result in behavioural changes, which can alter the spread of infectious diseases. Healthy individuals can express generalized social distancing or actively avoid the sources of infection, while infected individuals can show passive or active self-isolation. Amphibians are globally threatened by serious contagious diseases, yet their behavioural responses to infections are very scarcely known. We studied behavioural changes in agile frog (Rana dalmatina) juveniles upon exposure to aRanavirus(Rv). We performed classic choice tests in chambers containing a conspecific infected withRvin one end compartment and a non-infected conspecific in the other end, with anRv-infected or non-infected focal individual in the central compartment. We found that both non-infected andRv- infected focal individuals spatially avoided infected conspecifics, while there were no signs of generalized social distancing, nor self-isolation. Spatial avoidance of infected conspecifics may effectively hinder disease transmission. On the other hand, the absence of self-isolation by infected individuals may facilitate it. Our finding that infected individuals spent more time near the non-infected than infected conspecifics suggests that the strong behavioural drive to avoid infected conspecifics may not be silenced by infection, possibly to prevent secondary infections. The observation that infected focal individuals did not spend more time near conspecifics than non-infected focals renders it unlikely that the pathogen manipulated host behaviour to aid disease spread. More research is urgently needed to understand under what circumstances behavioural responses can help amphibians cope with infections, and how that affects disease dynamics in natural populations.GRAPHICAL ABSTRACT
A 3T investigation ofB1+-inhomogeneity tolerance in MP2RAGE-basedR1-mapping by calculating second contrast that permits previously problematic sequence parameters
Authors: Ruijters Lenno , Lund Torben Ellegaard , Vinding Mads Sloth 
Published: April 2024

AbstractPurposeRegarding in vivo, robustR1-mapping, the goal of the present paper is twofold. First, to verify that non-bijective mapping in MP2RAGE imaging can be resolved through a 2D look-up-table approach. Second, that the expanded parameter space from this can be used to improveB1+-inhomogeneity tolerance without other prerequisites.TheoryBy deriving a second contrast from the magnitude images of the MP2RAGE acquisition, ambiguities in the original MP2RAGE image resulting from non-bijective transfer curves can be resolved. Such ambiguities may occur when protocols are optimised, e.g., for higherB1+-inhomogeneity tolerance. A 2D look-up-table approach combines the available information to resolve these ambiguities during mapping.MethodsAt 3T, we acquired MP2RAGE images with standard acquisition parameters and (non-bijective) parameters optimised forB1+-inhomogeneity tolerance. From three subjects across multiple sessions, we assessed theB1+-inhomogeneity tolerance through excitation pulse amplitude scalings.ResultsTheR1-maps resulting from theB1+-optimised protocols showed greatly reducedB1+-effects across images, but without additional scanner time. Meanwhile these maps could only successfully be derived by a 2D look-up-table approach.ConclusionWe show that it is possible to optimise forB1+-inhomogeneity tolerance in MP2RAGE through sequence parameter settings, while still successfully estimating theR1-map with a 2D look-up-table approach. This without the need for an additionalB1+-map. The increased parameter space enabled by the 2D look-up-table approach may further be used to adjust MP2RAGE acquisitions for improved scan times, SNR and/or CNR.
Four centuries of commercial whaling eroded 11,000 years of population stability in bowhead whales
Authors: Westbury Michael V. , Brown Stuart C , Cabrera Andrea A. , Morales Hernán E , Ma Jilong , Rey-Iglesia Alba , Dyke Arthur , Scharff-Olsen Camilla Hjorth , Scott Michael B. , Wiig Øystein , Bachmann Lutz , Kovacs Kit M. , Lydersen Christian , Ferguson Steven H. , Racimo Fernando , Szpak Paul , Fordham Damien A. , Lorenzen Eline D. 
Published: April 2024

SummaryThe bowhead whale, an Arctic endemic, was heavily overexploited during commercial whaling between the 16th-20th centuries1. Current climate warming, with Arctic amplification of average global temperatures, poses a new threat to the species2. Assessing the vulnerability of bowhead whales to near-future predictions of climate change remains challenging, due to lacking data on population dynamics prior to commercial whaling and responses to past climatic change. Here, we integrate palaeogenomics and stable isotope (δ13C andδ15N) analysis of 201 bowhead whale fossils from the Atlantic Arctic with palaeoclimate and ecological modelling based on 823 radiocarbon dated fossils, 151 of which are new to this study. We find long-term resilience of bowhead whales to Holocene environmental perturbations, with no obvious changes in genetic diversity or population structure, despite large environmental shifts and centuries of whaling by Indigenous peoples prior to commercial harvests. Leveraging our empirical data, we simulated a time-series model to quantify population losses associated with commercial whaling. Our results indicate that commercial exploitation induced population subdivision and losses of genetic diversity that are yet to be fully realised; declines in genetic diversity will continue, even without future population size reductions, compromising the species’ resilience to near-future predictions of Arctic warming.
Asymmetric Allostery in Estrogen Receptor-α Homodimers Drives Responses to the Ensemble of Estrogens in the Hormonal Milieu
Authors: Min Charles K. , Nwachukwu Jerome C. , Hou Yingwei , Russo Robin J. , Papa Alexandra , Min Jian , Peng Rouming , Kim Sung Hoon , Ziegler Yvonne , Rangarajan Erumbi S. , Izard Tina , Katzenellenbogen Benita S. , Katzenellenbogen John A. , Nettles Kendall W. 
Published: April 2024

AbstractThe estrogen receptor-α (ER) is thought to function only as a homodimer, but responds to a variety of environmental, metazoan, and therapeutic estrogens at sub-saturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations —receptor conformational heterodimers—mimicking the binding of two different ligands. Molecular dynamics simulations showed that the pairs of different ligand poses changed the correlated motion across the dimer interface to generate asymmetric communication between the dimer interface, the ligands, and the surface binding sites for epigenetic regulatory proteins. By examining binding of the same ligand in crystal structures of ER in the agonist versus antagonist conformers, we also showed that these allosteric signals are bidirectional. The receptor conformer can drive different ligand binding modes to support agonist versus antagonist activity profiles, a revision of ligand binding theory that has focused on unidirectional signaling from ligand to the coregulator binding site. We also observed differences in the allosteric signals between ligand and coregulator binding sites in the monomeric versus dimeric receptor, and when bound by two different ligands, states that are physiologically relevant. Thus, ER conformational heterodimers integrate two different ligand-regulated activity profiles, representing new modes for ligand-dependent regulation of ER activity.SignificanceThe estrogen receptor-α (ER) regulates transcription in response to a hormonal milieu that includes low levels of estradiol, a variety of environmental estrogens, as well as ER antagonists such as breast cancer anti-hormonal therapies. While ER has been studied as a homodimer, the variety of ligand and receptor concentrations in different tissues means that the receptor can be occupied with two different ligands, with only one ligand in the dimer, or as a monomer. Here, we use X-ray crystallography and molecular dynamics simulations to reveal a new mode for ligand regulation of ER activity whereby sequence-identical homodimers can act as functional or conformational heterodimers having unique signaling characteristics, with ligand-selective allostery operating across the dimer interface integrating two different signaling outcomes.
Compressed sensing based approach identifies modular neural circuitry driving learned pathogen avoidance
Authors: Hallacy Timothy , Yonar Abdullah , Ringstad Niels , Ramanathan Sharad 
Published: April 2024

AbstractAn animal’s survival hinges on its ability to integrate past information to modify future behavior. The nematodeC. elegansadapts its behavior based on prior experiences with pathogen exposure, transitioning from attraction to avoidance of the pathogen. A systematic screen for the neural circuits that integrate the information of previous pathogen exposure to modify behavior has not been feasible because of the lack of tools for neuron type specific perturbations. We overcame this challenge using methods based on compressed sensing to efficiently determine the roles of individual neuron types in learned avoidance behavior. Our screen revealed that distinct sets of neurons drive exit from lawns of pathogenic bacteria and prevent lawn re-entry. Using calcium imaging of freely behaving animals and optogenetic perturbations, we determined the neural dynamics that regulate one key behavioral transition after infection: stalled re-entry into bacterial lawns. We find that key neuron types govern pathogen lawn specific stalling but allow the animal to enter nonpathogenicE. colilawns. Our study shows that learned pathogen avoidance requires coordinated transitions in discrete neural circuits and reveals the modular structure of this complex adaptive behavioral response to infection.
Population genomics ofPlasmodium ovalespecies in sub-Saharan Africa
Authors: Carey-Ewend Kelly , Popkin-Hall Zachary R. , Simkin Alfred , Muller Meredith , Hennelly Chris , He Wenqiao , Moser Kara A. , Gaither Claudia , Niaré Karamoko , Aghakanian Farhang , Feleke Sindew , Brhane Bokretsion G. , Phanzu Fernandine , Mwandagalirwa Kashamuka , Aydemir Ozkan , Sutherland Colin J. , Ishengoma Deus S. , Ali Innocent M. , Ngasala Billy , Kalonji Albert , Tshefu Antoinette , Parr Jonathan B. , Bailey Jeffrey A. , Juliano Jonathan J. , Lin Jessica T. 
Published: April 2024

AbstractPlasmodium ovale curtisi(Poc)andPlasmodium ovale wallikeri(Pow) are relapsing malaria parasites endemic to Africa and Asia that were previously thought to represent a single species. Amid increasing detection of ovale malaria in sub-Saharan Africa, we performed a population genomic study of both species across the continent. We conducted whole-genome sequencing of 25 isolates from Central and East Africa and analyzed them alongside 20 previously published African genomes. Isolates were predominantly monoclonal (43/45), with their genetic similarity aligning with geography.Powshowed lower average nucleotide diversity (1.8×10−4) across the genome compared toPoc(3.0×10−4) (p < 0.0001). Signatures of selective sweeps involving the dihydrofolate reductase gene were found in both species, as were signs of balancing selection at the merozoite surface protein 1 gene. Differences in the nucleotide diversity ofPocandPowmay reflect unique demographic history, even as similar selective forces facilitate their resilience to malaria control interventions.
The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center inDrosophila
Authors: Jones Joseph D. , Holder Brandon L. , Montgomery Andrew C. , McAdams Chloe V. , He Emily , Burns Anna E. , Eiken Kiran R. , Vogt Alex , Velarde Adriana I. , Elder Alexandra J. , McEllin Jennifer A. , Dissel Stephane 
Published: April 2024

AbstractSleep is a behavior that is conserved throughout the animal kingdom. Yet, despite extensive studies in humans and animal models, the exact function or functions of sleep remain(s) unknown. A complicating factor in trying to elucidate the function of sleep is the complexity and multiplicity of neuronal circuits that are involved in sleep regulation. It is conceivable that distinct sleep-regulating circuits are only involved in specific aspects of sleep and may underlie different sleep functions. Thus, it would be beneficial to assess the contribution of individual circuits in sleep’s putative functions. The intricacy of the mammalian brain makes this task extremely difficult. However, the fruit flyDrosophila melanogaster,with its simpler brain organization, available connectomics, and unparalleled genetics offers the opportunity to interrogate individual sleep-regulating centers. InDrosophila, neurons projecting to the dorsal Fan-Shaped Body (dFB) have been proposed to be key regulators of sleep, particularly sleep homeostasis. We recently demonstrated that the most widely used genetic tool to manipulate dFB neurons, the 23E10-GAL4 driver, expresses in two sleep-regulating neurons (VNC-SP neurons) located in the Ventral Nerve Cord (VNC), the fly analog of the vertebrate spinal cord. Since most data supporting a role for the dFB in sleep regulation have been obtained using 23E10-GAL4, it is unclear whether the sleep phenotypes reported in these studies are caused by dFB neurons or VNC-SP cells. A recent publication replicated our finding that 23E10-GAL4 contains sleep-promoting neurons in the VNC. However, it also proposed that the dFB is not involved in sleep regulation at all, but this suggestion was made using genetic tools that are not dFB-specific and a very mild sleep deprivation protocol. In this study, using a newly created dFB-specific genetic driver line, we demonstrate that the majority of 23E10-GAL4 dFB neurons can promote sleep when activated and that these neurons are involved in sleep homeostasis. We also show that dFB neurons require stronger stimulation than VNC-SP cells to promote sleep. In addition, we demonstrate that dFB-induced sleep can consolidate Short-Term Memory (STM) into Long-Term Memory (LTM), suggesting that the benefit of sleep on memory is not circuit-specific. Finally, we show that dFB neurons are neurochemically heterogeneous and can be divided in 3 populations. Most dFB neurons express both glutamate and acetylcholine, while a minority of cells express only one of these two neurotransmitters. Importantly, dFB neurons do not express GABA, as previously suggested. Using neurotransmitter-specific dFB tools, our data also points at cholinergic dFB neurons as particularly potent at regulating sleep and sleep homeostasis.
GLMMcosinor: Flexible cosinor modeling with a generalized linear mixed modeling framework to characterize rhythmic time series
Authors: Parsons Rex , Jayasinghe Oliver , White Nicole , Chunduri Prasad , Rawashdeh Oliver 
Published: April 2024

AbstractThe complexity, volume, and importance of time series data across various research domains highlight the necessity for tools that can efficiently analyze, visualize, and extract insights. Cosinor modeling is a widely used methodology to estimate or compare rhythmic characteristics in time series datasets. Time series are widely used in biomedical and clinical research studies, with a large amount of research focusing on circadian rhythms in physiology and their relationship to health outcomes. However, existing software for cosinor modeling fails to effectively equip researchers to analyze their data, often due to the hierarchical structure of the data (e.g., repeated measures over time) or non-Gaussian response variables being modeled. Here, we present GLMMcosinor, an R package for fitting the cosinor model to rhythmic time series, using a Generalized Linear Mixed Modeling framework (glmmTMB). This software extends cosinor modeling to non-Gaussian and hierarchical data due to the flexibility offered by glmmTMB. It offers multiple additional features unavailable in other cosinor modeling packages that use the linearized cosinor model or circacompare (which we previously developed), which uses nonlinear regression. GLMMcosinor includes several additional features to interpret, test, and visualize the produced models and can fit models with multiple cosinor components. A detailed description of the use of GLMMcosinor is available within the package’s online documentation and vignettes. The GLMMcosinor R package is available from GitHub (https://github.com/ropensci/GLMMcosinor), CRAN, rOpenSci, and the R-universe. A shiny app is also available and can fit and visualize a model with GLMMcosinor without having to write R code (https://github.com/RWParsons/GLMMcosinor-shinyapp).Key PointsGLMMcosinor is an R Package for flexible cosinor modeling, a method used to estimate cyclic rhythm characteristics.It uses a generalized linear mixed modeling framework (glmmTMB) to allow the user to fit data with non-Gaussian response variables and hierarchical data structures.GLMMcosinor is a well documented and feature rich package allowing users to easily fit, interpret and visualize cosinor models.GLMMcosinor supports modeling of a wider range of experimental and observation datasets.