bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structured demographic buffering: A framework to explore the environment drivers and demographic mechanisms underlying demographic buffering
Authors: Gascoigne Samuel J L , Kajin Maja , Tuljapurkar Shripad , Santos Gabriel Silva , Compagnoni Aldo , Steiner Ulrich K , Vinton Anna C , Jaggi Harman , Sepil Irem , Salguero-Gómez Roberto 
Published: July 2023

ABSTRACTEnvironmental stochasticity is a key determinant of population viability. Decades of work exploring how environmental stochasticity influences population dynamics have highlighted the ability of some natural populations to limit the negative effects of environmental stochasticity, one of these strategies being demographic buffering. Whilst various methods exist to quantify demographic buffering, we still do not know which environment factors and demographic characteristics are most responsible for the demographic buffering observed in natural populations. Here, we introduce a framework to quantify the relative effects of three key drivers of demographic buffering: environment components (e.g., temporal autocorrelation and variance), population structure, and demographic rates (e.g., progression and fertility). Using Integral Projection Models, we explore how these drivers impact the demographic buffering abilities of three plant species with different life histories and demonstrate how our approach successfully characterises a population’s capacity to demographically buffer against environmental stochasticity in a changing world.
Neuromolecular responses in disrupted mutualistic cleaning interactions under future environmental conditions
Authors: Ramírez-Calero S. , Paula J. R. , Otjacques E. , Ravasi T. , Rosa R. , Schunter C. 
Published: July 2023

ABSTRACTMutualistic interactions, which constitute some of the most advantageous interactions among fish species, are highly vulnerable to environmental changes. A key mutualistic interaction is the cleaning service rendered by the cleaner wrasse,Labroides dimidiatus, which involves intricate processes of social behaviour to remove ectoparasites from client fish and can be altered in near-future environmental conditions. Here, we evaluated the neuromolecular mechanisms behind the behavioural disruption of cleaning interactions in response to future environments. We subjected cleaner wrasses and surgeonfish (Acanthurus leucosternon, serving as clients) to elevated temperature (Warming, 32°C), increased levels of CO2(High CO2, 1000 ppm), and a combined condition of elevated CO2and temperature (Warming & High CO2, 32°C & 1000 ppm) for 28 days. Each of these conditions resulted in behavioural disruptions concerning the motivation to interact and the quality of interaction (High CO2-80.7%, Warming – 92.6%, Warming & High CO2-79.5%,p<0.001). Using transcriptomic of the fore-, mid-, and hindbrain, we discovered that most transcriptional reprogramming in both species under warming conditions occurred primarily in the hind- and forebrain. The associated functions under warming were linked to stress, heat shock proteins, hypoxia, and behaviour. In contrast, elevated CO2exposure affected a range of functions associated with GABA, behaviour, visual perception, and circadian rhythm. Interestingly, in the combined Warming & High CO2condition, we did not observe any expression changes of behaviour. However, we did find signs of endoplasmic reticulum stress and apoptosis, suggesting not only an additive effect of the environmental conditions but also a trade-off between physiological performance and behaviour in the cleaner wrasse. We suggest that impending environmental shifts can affect the behaviour and molecular processes that sustain mutualistic interactions betweenL. dimidiatusand its clients, which could have a cascading effect on their adaptation potential and possibly cause large-scale impacts on coral reef ecosystems.
Coevolution-driven method for efficiently simulating conformational changes in proteins reveals molecular details of ligand effects in the β2AR receptor
Authors: Mitrovic Darko , Chen Yue , Marciniak Antoni , Delemotte Lucie 
Published: July 2023

AbstractWith the advent of AI-powered structure prediction, the scientific community is inching ever closer to solving protein folding. An unresolved enigma, however, is to accurately, reliably and deterministically predict alternative conformational states that are crucial for the function of e.g. transporters, receptors or ion channels where conformational cycling is innately coupled to protein function. Accurately discovering and exploring all conformational states of membrane proteins has been challenging due to the need to retain atomistic detail while enhancing the sampling along interesting degrees of freedom. The challenges include but are not limited to finding which degrees of freedom are relevant, how to accelerate the sampling along them, and then quantifying the populations of each micro- and macrostate. In this work, we present a methodology that finds the relevant degrees of freedom by combining evolution and physics through machine learning and apply it to the β2 adrenergic receptor conformational sampling. In addition to predicting new conformations that are beyond the training set, we have computed free energy surfaces associated with the protein’s conformational landscape. We then show that the methodology is able to quantitatively predict the effect of an array of ligands on the β2 adrenergic receptor activation, and that the full conformational landscape, including states related to biased signaling, is discovered using this procedure. Lastly, we also stake out the structural determinants of activation and inactivation pathway signaling through different ligands.
Three-dimensional study of spur morphogenesis in the flower ofStaphisagria picta(Ranunculaceae) – from cellular level to organ scale
Authors: Delpeuch Pauline , Nadot Sophie , Belcram Katia , Plumerault Antoine , Damerval Catherine , Jabbour Florian 
Published: July 2023

AbstractFloral spurs are invaginations borne by perianth organs (petals and/or sepals) that have evolved repeatedly in various angiosperm clades. They typically store nectar and can limit the access of pollinators to this reward, resulting in pollination specialization that can lead to speciation in both pollinator and plant lineages.Despite the ecological and evolutionary importance of nectar spurs, the cellular mechanisms involved during spur development have only been described in detail in a handful of species, primarily with respect to epidermal cells. These studies show that the mechanisms involved are taxon-specific.Using confocal microscopy and automated 3D image analysis, we studied spur morphogenesis inStaphisagria picta(Ranunculaceae) and showed that the process is marked by an early phase of dominant cell proliferation, followed by a phase of anisotropic (directional) cell expansion.The comparison withAquilegia, another taxon of Ranunculaceae with spurred petals, revealed that the convergence in form between the spurs of both taxa is obtained by partially similar developmental processes. The analytical pipeline designed here is an efficient method to visualize in 3D each cell of a developing organ, paving the way for future comparative studies of organ morphogenesis in multicellular eukaryotes.HighlightA new method of 3D analysis of plant tissues at the cellular level revealed that spur morphogenesis inStaphisagria pictais marked by an early phase of dominant cell proliferation, followed by a phase of anisotropic cell expansion. Floral spur development is analysed for the first time quantitatively, taking into account all tissues composing the organ, namely epidermis and parenchyma.
Impact Evaluation of Significant Feature Set in Cross Project for Defect Prediction through Hybrid Feature Selection in Multiclass
Authors: Gul Sana , Faiz Rizwan Bin , Aljaidi Mohammad , Samara Ghassan , Alsarhan Ayoub , al-Qerem Ahmad 
Published: July 2023

AbstractCross-project defect prediction (CPDP) is a significant way of defect identification in the project. In cross-project defect prediction, we extract knowledge from the source project and apply that learned knowledge to predict labels for the target project. However, the model performance can be affected by features that are insignificant and irrelevant. Hybrid feature selection (HFS) can play a significant role in achieving high prediction accuracy by selecting significant and only relevant features. Our aim is to explore effect of significant feature selection through a hybrid approach upon cross-project (CP) defect prediction for datasets which are multi-class in nature. We leveraged the strengths of Random Forest (RF) and Recursive Feature Elimination Cross Validation (RFECV) which can constructively select few features which are significant. The design of our controlled experiment is 1 Factor 2 Treatments (1F2T). Exploratory Data Analysis (EDA) proves that all versions of PROMISE repository are multi class and have duplicated rows in data, distribution gap among values, and imbalance classes. Hence after removing duplicated rows, reducing the gap present in distribution of data, and balancing classes, we selected significant feature set through Hybrid approach i.e. Random Forest (RF) and Recursive Feature Elimination Cross Validation (RFECV). We used Convolutional Neural Network (CNN) as a classifier to predict Cross project defects along with SoftMax as the last layer. Our experimental setup resulted in the average 78% prediction accuracy measure of all 14 versions in terms of AUC. Our experimental result showed that there is significant impact of HFS on defect prediction accuracy for different datasets in the CP.
Spatial analysis of environmental factors at found locations of orphaned mammals (Didelphis virginiana,Procyon lotor,Sciurus carolinensis, andSylvilagus floridanus) in Champaign County, Illinois, USA
Authors: Heniff Stephanie , Sander William , Elzinga Colleen , Varga Csaba , Brown William Marshall , Sander Samantha J. 
Published: July 2023

AbstractInteractions between people and wildlife are increasing as developments encroach on nature. Concurrently, neonatal and juvenile mammals are presented to rehabilitation centers as real or perceived “orphans”, believed to be lacking appropriate parental care for survival. Four common orphaned mammals presented to wildlife rehabilitation facilities are the Virginia opossum (Didelphis virginiana,DIVI), common raccoon (Procyon lotor,PRLO), eastern gray squirrel (Sciurus carolinensis,SCCA), and eastern cottontail rabbit (Sylvilagus floridanus,SYFL). As some individuals are unnecessarily taken from their habitat, there is a benefit to characterizing where they are collected. This study utilized Geographic Information System to examine the spatial relationship between the environment and originating locations of orphans presented to the University of Illinois Wildlife Medical Clinic within Champaign County from 2015-2020 (99 Virginia opossums, 80 common raccoons, 441 eastern gray squirrels, and 602 eastern cottontails). Environmental factors evaluated included percent tree canopy, land cover classification, and distance to water. Overall, these species were frequently found in highly developed areas (p < 0.001), near water (p < 0.027), with a low percent canopy (p < 0.001). Our analysis identifies environments associated with greater human-wildlife interactions and opportunities for targeted educational outreach.
LEF1 isoforms regulate cellular senescence and aging
Authors: Jia Minxue , Sayed Khaled , Kapetanaki Maria G. , Dion William , Rosas Lorena , Irfan Saad , Valenzi Eleanor , Mora Ana L. , Lafyatis Robert A. , Rojas Mauricio , Zhu Bokai , Benos Panayiotis V. 
Published: July 2023

ABSTRACTBackgroundThe study of aging and its mechanisms, such as cellular senescence, has provided valuable insights into age-related pathologies, thus contributing to their prevention and treatment. The current abundance of high throughput data combined with the surge of robust analysis algorithms has facilitated novel ways of identifying underlying pathways that may drive these pathologies.MethodsWith the focus on identifying key regulators of lung aging, we performed comparative analyses of transcriptional profiles of aged versus young human subjects and mice, focusing on the common age-related changes in the transcriptional regulation in lung macrophages, T cells, and B immune cells. Importantly, we validated our findings in cell culture assays and human lung samples.ResultsWe identified Lymphoid Enhancer Binding Factor 1 (LEF1) as an important age-associated regulator of gene expression in all three cell types across different tissues and species. Follow-up experiments showed that the differential expression of long and short LEF1 isoforms is a key regulatory mechanism of cellular senescence. Further examination of lung tissue from patients with Idiopathic Pulmonary Fibrosis (IPF), an age-related disease with strong ties to cellular senescence, we demonstrated a stark dysregulation of LEF1.ConclusionsCollectively, our results suggest that the LEF1 is a key factor of aging, and its differential regulation is associated with human and murine cellular senescence.
Coordination of cell cycle and morphogenesis during organ formation
Authors: Matthew Jeffrey , Vishwakarma Vishakha , Le Thao Phuong , Agsunod Ryan A. , Chung SeYeon 
Published: July 2023

AbstractOrgan formation requires precise regulation of cell cycle and morphogenetic events. Using theDrosophilaembryonic salivary gland (SG) as a model, we uncover the role of the SP1/KLF transcription factor Huckebein (Hkb) in coordinating cell cycle regulation and morphogenesis. Thehkbmutant SG exhibits defects in invagination positioning and organ size due to abnormal death of SG cells. Normal SG development involves distal-to-proximal progression of endoreplication (endocycle), whereashkbmutant SG cells undergo abnormal cell division, leading to cell death. Hkb represses the expression of key cell cycle and pro-apoptotic genes in the SG. Knockdown ofcyclin Eorcyclin-dependent kinase 1,or overexpression offizzy-relatedrescues most of the morphogenetic defects observed in thehkbmutant SG. These results indicate that Hkb plays a critical role in controlling endoreplication by regulating the transcription of key cell cycle effectors to ensure proper organ formation.
Eliminating Malaria Vectors with Precision Guided Sterile Males
Authors: Smidler Andrea L. , Apte Reema A. , Pai James J. , Chow Martha L. , Chen Sanle , Mondal Agastya , Sánchez C. Héctor M. , Antoshechkin Igor , Marshall John M. , Akbari Omar S. 
Published: July 2023

AbstractControlling the principal African malaria vector, the mosquitoAnopheles gambiae, is considered essential to curtail malaria transmission. However existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet theA. gambiaetoolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass-releases of non-biting, non-driving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here we develop precision guided Sterile Insect Technique (pgSIT) in the mosquitoA. gambiaefor inducible, programmed male-sterilization and female-elimination for wide scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male-sterility and >99.9% female-lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce population suppression in cage trials, and are predicted to eliminate wildA. gambiaepopulations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, for the first time enabling scalable SIT-like confinable suppression in the species.
The timing of cellular events: a stochastic vs deterministic perspective
Authors: Ham Lucy , Coomer Megan A. , Öcal Kaan , Grima Ramon , Stumpf Michael P.H. 
Published: July 2023

AbstractChanges in cell state are driven by key molecular events whose timing can often be measured experimentally. Of particular interest is the time taken for the levels of RNA or protein molecules to reach a critical threshold defining the triggering of a cellular event. While this mean trigger time can be estimated by numerical integration of deterministic models, these ignore intrinsic noise and hence their predictions may be inaccurate. Here we study the differences between deterministic and stochastic model predictions for the mean trigger times using simple models of gene expression, post-transcriptional feedback control, and enzyme-mediated catalysis. By comparison of the two predictions, we show that when promoter switching is present there exists a transition from a parameter regime where deterministic models predict a longer trigger time than stochastic models to a regime where the opposite occurs. Furthermore, the ratio of the trigger times of the two models can be large, particularly for auto-regulatory genetic feedback loops. Our theory provides intuitive insight into the origin of these effects and shows that deterministic predictions for cellular event timing can be highly inaccurate when molecule numbers are within the range known for many cells.
Membrane mechanics dictate axonal morphology and function
Authors: Griswold Jacqueline M. , Bonilla-Quintana Mayte , Pepper Renee , Lee Christopher T. , Raychaudhuri Sumana , Ma Siyi , Gan Quan , Syed Sarah , Zhu Cuncheng , Bell Miriam , Suga Mitsuo , Yamaguchi Yuuki , Chéreau Ronan , Nägerl U. Valentin , Knott Graham , Rangamani Padmini , Watanabe Shigeki 
Published: July 2023

AbstractAxons are thought to be ultrathin membrane cables of a relatively uniform diameter, designed to conduct electrical signals, or action potentials. Here, we demonstrate that unmyelinated axons are not simple cylindrical tubes. Rather, axons have nanoscopic boutons repeatedly along their length interspersed with a thin cable with a diameter of ∼60 nm like pearls-on-a-string. These boutons are only ∼200 nm in diameter and do not have synaptic contacts or a cluster of synaptic vesicles, hence non-synaptic. Ourin silicomodeling suggests that axon pearling can be explained by the mechanical properties of the membrane including the bending modulus and tension. Consistent with modeling predictions, treatments that disrupt these parameters like hyper- or hypo-tonic solutions, cholesterol removal, and non-muscle myosin II inhibition all alter the degree of axon pearling, suggesting that axon morphology is indeed determined by the membrane mechanics. Intriguingly, neuronal activity modulates the cholesterol level of plasma membrane, leading to shrinkage of axon pearls. Consequently, the conduction velocity of action potentials becomes slower. These data reveal that biophysical forces dictate axon morphology and function and that modulation of membrane mechanics likely underlies plasticity of unmyelinated axons.
Ran-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos
Authors: Kiyomitsu Ai , Nishimura Toshiya , Hwang Shiang Jyi , Ansai Satoshi , Kanemaki Masato T. , Tanaka Minoru , Kiyomitsu Tomomi 
Published: July 2023

AbstractDespite drastic cellular changes during cleavage divisions, a mitotic spindle is assembled in each blastomere to accurately segregate duplicated chromosomes. Recent studies indicate that early embryonic divisions are highly error-prone in bovines and humans. However, processes and mechanisms of embryonic spindle assembly remain little understood in vertebrates. Here, we established live functional assay systems in medaka fish (Oryzias latipes) embryos by combining CRISPR knock-in with an auxin-inducible degron technology. In contrast to mammals, mitoses during cleavage divisions are very rapid (<12 min), but segregation errors are rarely observed. Importantly, we found that the Ran-GTP gradient assembles a specialized, dense microtubule network at the spindle midplane during metaphase, which is essential for faithful chromosome segregation in early embryos. In contrast, Ran-GTP becomes dispensable for chromosome segregation in later stages, where spindles are morphologically remodeled into short, somatic-like spindles lacking the dense microtubule network. We propose that the specialized Ran-based spindle structure ensures high fidelity of chromosome segregation in large, vertebrate early embryos.
Chromosome-scale genome assembly ofTinospora sagittata(Oliv.) Gagnep. enhances identifying genes involved in the biosynthesis of jatrorrhizine
Authors: Alami Mohammad Murtaza , Shu Shaohua , Liu Sanbo , Ouyang Zhen , Zhang Yipeng , Lv Meijia , Sang Yonghui , Gong Dalin , Yang Guozheng , Feng Shengqiu , Mei Zhinan , Xie De-Yu , Wang Xuekui 
Published: July 2023

SummaryTinospora sagittata(Oliv.) Gagnep. is an important medicinal tetraploid plant in the Menispermaceae family. Its tuber, namely “Radix Tinosporae” used in Traditional Chinese Medicine, is rich in medicinal terpenoids and benzylisoquinoline alkaloids (BIAs), To enhance understanding the biosynthesis of medicinal compounds, we, herein, report the assembly of a high quality chromosome-scale genome with both PacBio HiFi and Illumina sequencing technologies. The size of assembled genome was 2.33 Gb consisting of 4070 scaffolds (N50=42.06Mb), of which 92.05% were assigned to 26 pseudochromosomes in A and B sub-genomes. A phylogenetic analysis with theT. sagittataand other 16 plant genomes estimated the evolutionary placement ofT. sagittataand its divergence time in Ranunculales. Further genome evolution analysis characterized one round tandem duplication about 1.5 million years ago (MYA) and one whole-genome duplication (WGD) about 86.9 MYA. WGD contributed to the duplication of clade-specific cytochrome P450 gene family in Ranunculales. Moreover, sequencing mining obtained genome-wide genes involved in the biosynthesis of alkaloids and terpenoids.TsA02G014550, one candidate, was functionally characterized to catalyze the formation of (S)-canadine in the jatrorrhizine biosynthetic pathway. Taken together, the assembled genome ofT. sagittataprovides useful sequences to understand the biosynthesis of jatrorrhizine and other BIAs in plants.
Large effects and the infinitesimal model
Authors: Parsons Todd L. , Ralph Peter L. 
Published: July 2023

AbstractThe infinitesimal model of quantitative genetics relies on the Central Limit Theorem to stipulate that under additive models of quantitative traits determined by many loci having similar effect size, the difference between an offspring’s genetic trait component and the average of their two parents’ genetic trait components is Normally distributed and independent of the parents’ values. Here, we investigate how the assumption of similar effect sizes affects the model: in particular, if the tail of the effect size distribution is polynomial with exponentα <2, then sums of effects should be well-approximated by a “stable distribution”, and find tail exponents between 1 and 2 in effect sizes estimated by genome-wide association studies of many human disease-related traits. We show that the independence of offspring trait deviations from parental averages in many cases implies a Gaussian distribution, suggesting that non-Gaussian models of trait evolution must explicitly track the underlying genetics, at least for loci of large effect. We also characterize possible limiting trait distributions of the infinitesimal model with infinitely divisible noise distributions, and compare our results to simulations.