bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating recent and historical effective population size of marine and freshwater sticklebacks
Authors: Feng Xueyun , Löytynoja Ari , Merilä Juha 
Published: May 2023

AbstractEffective population size (Ne) is a quantity of central importance in evolutionary biology and population genetics, but often notoriously challenging to estimate. Analyses ofNeare further complicated by the many interpretations of the concept and the alternative approaches to quantifyNeutilising widely different properties of the data. On the other hand, alternative methods are informative for different time scales such that a set of complementary methods should allow piecing together the entire continuum ofNefrom a few generations before the present to the distant past. To test this in practice, we inferred the continuum ofNefor 45 nine-spined stickleback populations (Pungitius pungitius) using whole-genome data. We found that the marine populations had the largest historical and recentNe, followed by coastal and other freshwater populations. We identified the impact of both recent and historical gene flow on theNeestimates obtained from different methods and found that simple summary statistics are informative in comprehending the events in the very recent past. Overall, our analyses showed that the coalescence-based trajectories ofNein the recent past and the LD-based estimates of near-contemporaryNeare incongruent, though in some cases the incongruence might be explained by specific demographic events. Despite still lacking accuracy and resolution for the very recent past, the sequentially Markovian coalescent-based methods seem to provide the most meaningful interpretation of the real-lifeNevarying across time.
Coevolution increases robustness to extinctions in mutualistic but not antagonistic communities
Authors: Pedraza Fernando , Gawecka Klementyna A. , Bascompte Jordi 
Published: May 2023

AbstractCo-extinctions may exacerbate the current biodiversity crisis. Yet, we do not understand all the factors that shape the robustness of communities to the loss of species. Here we analyse how coevolution influences the robustness of mutualistic and antagonistic communities. We find that coevolution increases robustness in mutualism but reduces it in antagonism. These differences are due to coevolution altering the density of interactions in communities. The largest changes to robustness occur when coevolutionary selection is strong. Yet, the effect size of coevolution on robustness depends on the size of the community. Our results may broaden the suite of mechanisms affecting the resilience of ecological communities. These insights may inform efforts to reduce the risk of species loss in the face of global change.
HOIL1 regulates group 3 innate lymphoid cell numbers in the colon and protects against systemic dissemination, colonic ulceration, and lethality fromCitrobacter rodentiuminfection
Authors: Hartley Victoria L. , Qaqish Arwa M. , Wood Matthew J. , Studnicka Brian T. , Iwai Kazuhiro , Liu Ta-Chiang , MacDuff Donna A. 
Published: May 2023

AbstractHOIL1-deficient patients experience chronic intestinal inflammation and diarrhea as well as increased susceptibility to certain bacterial infections. HOIL1 is a component of the linear ubiquitin chain assembly complex (LUBAC) that regulates immune signaling pathways including NF-κB-activating pathways. We have shown previously that HOIL1 is essential for survival followingCitrobacter rodentiumgastrointestinal infection of mice, but the mechanism of protection by HOIL1 was not examined.C. rodentiumis a murine model for human attaching and effacing (A/E) pathogens, enteropathogenic and enterohemorrhagicEscherichia coli,that cause diarrhea and food-borne illnesses, and lead to severe disease in children and immunocompromised individuals. In this study, we found thatC. rodentiuminfection caused severe colitis and dissemination ofC. rodentiumto systemic organs inHoil1-/-mice. HOIL1 was important in radiation-resistant cells and in the innate immune response to limit early replication ofC. rodentiumin the intestine, and to modulate induction of inflammatory cytokines. Using cell type-specific knock-out mice, we found that HOIL1 was dispensable in intestinal epithelial cells (IEC), but was required in CD11c- and lysozyme 2-expressing myeloid cells to prevent weight loss and systemic dissemination ofC. rodentium. While HOIL1-deficiency did not affect populations of neutrophils or macrophages, dendritic cells and group 3 innate lymphoid cell (ILC3) numbers were reduced, resulting in a defect in IL-22 induction duringC. rodentiuminfection. Understanding the role HOIL1 plays in limiting the pathogenesis of A/E lesion-forming bacteria will provide further insights into the innate immune response to gastrointestinal pathogens and inflammatory disorders.
Ethnopharmacological disease classification and bioprospecting: the diversity of plant drugs used to treat cancer
Authors: Thompson Jamie , Hawkins Julie 
Published: May 2023

AbstractCancer is a highly-diverse disease and as the second-leading cause of death worldwide is a focus of drug discovery research. Natural products have been shown to be a useful source of novel molecules for the treatment of cancer. It is likely there are many plants with undiscovered molecules of therapeutic value, however identifying new leads from among the vast diversity of plants is very challenging. Traditional knowledge might inform bioprospecting by predicting lineages of plants rich in therapeutically useful molecules. Here, we characterise the phylogenetic diversity of plants used traditionally to manage cancer. We demonstrate the independent and repeated targeting of specific lineages of plants by different peoples in different parts of the world. That the same lineages are used to treat different cancers is suggestive of independent discovery of therapeutic value. However, the lineages we report here as rich in plants used traditionally to treat cancer coincide with those for other ethnobotanical applications, and contain few plants with proven anti-cancer activity. It is likely that the traditional knowledge recorded and explored here is shaped by selection of plants conferring milder effects for treating wider symptoms, such as tiredness or nausea, rather than for halting tumour growth. Accurate prediction of useful plant lineages for cancer management requires more nuanced information than is commonly provided in ethnobotanical records.
Long-read genome assemblies for the study of chromosome expansion:Drosophila kikkawai,Drosophila takahashii,Drosophila bipectinata, andDrosophila ananassae
Authors: Leung Wilson , Torosin Nicole , Cao Weihuan , Reed Laura K , Arrigo Cindy , Elgin C R Sarah , Ellison Christopher E 
Published: May 2023

AbstractFlow cytometry estimates of genome sizes among species ofDrosophilashow a 3-fold variation, ranging from ∼127 Mb inDrosophila mercatorumto ∼400 Mb inDrosophila cyrtoloma. However, the assembled portion of the Muller F Element (orthologous to the fourth chromosome inDrosophila melanogaster) shows a nearly 14-fold variation in size, ranging from ∼1.3 Mb to > 18 Mb. Here, we present chromosome-level long read genome assemblies for fourDrosophilaspecies with expanded F Elements ranging in size from 2.3 Mb to 20.5 Mb. Each Muller Element is present as a single scaffold in each assembly. These assemblies will enable new insights into the evolutionary causes and consequences of chromosome size expansion.
Biochemical Pathways Represented by Gene Ontology Causal Activity Models Identify Distinct Phenotypes Resulting from Mutations in Pathways
Authors: Hill David P , Drabkin Harold J , Smith Cynthia L , Van Auken Kimberly M , D’Eustachio Peter 
Published: May 2023

AbstractGene inactivation can affect the process(es) in which that gene acts and causally downstream ones, yielding diverse mutant phenotypes. Identifying the genetic pathways resulting in a given phenotype helps us understand how individual genes interact in a functional network. Computable representations of biological pathways include detailed process descriptions in the Reactome Knowledgebase, and causal activity flows between molecular functions in Gene Ontology-Causal Activity Models (GO-CAMs). A computational process has been developed to convert Reactome pathways to GO-CAMs. Laboratory mice are widely used models of normal and pathological human processes. We have converted human Reactome GO-CAMs to orthologous mouse GO-CAMs, as a resource to transfer pathway knowledge between humans and model organisms. These mouse GO-CAMs allowed us to define sets of genes that function in a causally connected way. To demonstrate that individual variant genes from connected pathways result in similar but distinguishable phenotypes, we used the genes in our pathway models to cross-query mouse phenotype annotations in the Mouse Genome Database (MGD). Using GO-CAM representations of two related but distinct pathways, gluconeogenesis and glycolysis, we show that individual causal paths in gene networks give rise to discrete phenotypic outcomes resulting from perturbations of glycolytic and gluconeogenic genes. The accurate and detailed descriptions of gene interactions recovered in this analysis of well-studied processes suggest that this strategy can be applied to less well-understood processes in less well-studied model systems to predict phenotypic outcomes of novel gene variants and to identify potential gene targets in altered processes.SummaryGenes act in interconnected biological pathways, so single mutations can yield diverse phenotypes. To use the large body of mouse functional gene annotations, we converted human Gene Ontology-Causal Activity Models (GO-CAMs) of glucose metabolism to orthologous mouse GO-CAMs. We then queried phenotypes for mouse genes in these GO-CAMs and identified gene networks associated with discrete phenotypic outcomes due to perturbations of glycolysis and gluconeogenesis. This strategy can be extended to less well-understood processes and model systems to predict phenotypic outcomes.
High-throughput phenotyping of single nucleotide variants by linking transcriptomes to genotypes in single cells
Authors: Cooper Sarah E. , Coelho Matthew A. , Strauss Magdalena E. , Gontarczyk Aleksander M. , Wu Qianxin , Garnett Mathew J. , Marioni John C. , Bassett Andrew R. 
Published: May 2023

AbstractCRISPR screens with single-cell transcriptomic readouts are a valuable tool to understand the effect of genetic perturbations, but are currently limited because genotypes are inferred from the guide RNA identity. We have developed a technique that couples single-cell genotyping to transcriptomics of the same cells to enable screening for the effects of single nucleotide variants. Analysis of variants tiling across theJAK1gene demonstrates the importance of determining the precise genetic perturbation and classifies missense variants into three functional categories.
Genetic evidence for functions of Chloroplast CA inPyropia yezoensis: decreased CCM but increased starch accumulation
Authors: Zhang Baoyu , Liu Xueying , Xie Xiujun , Huan Li , Wang Hong , Shao Zhizhuo , Wang Guangce 
Published: May 2023

AbstractTo adapt to the change of intertidal environment, intertidal macroalgae have evolved complicated Ci utilization mechanism. However, our knowledge regarding the CO2 concentrating mechanism (CCM) of macroalgae is limited. Carbonic anhydrase (CA), a key component of CCM, plays important roles in many physiological reactions in various organisms. While there are a large number of genes encoding CA in the Pyropia yezoensis genome, the exact function of specific CA in P. yezoensis remains elusive. To explore the specific function of chloroplast CA in intertidal macroalgae, we produced chloroplast-localized βCA1 knockdown mutants of P. yezoensis through RNA interference, and Pyca1i mutants showed a notable decrease in leaf area and overall biomass, as well as decreased soluble protein and unsaturated fatty acid content under different DIC conditions. However, Pyca1i mutants showed relatively higher starch content compared to the wild-type. The activity of enzymes involved in Calvin cycle, photorespiration, Pentose-phosphate pathway and floridean starch synthesis of P.yezoensis indicated an effective starch accumulation pathway after interference of βCA1. All results suggest that the decreased activity of PyβCA1 impaired the CCM and development of thalli of P.yezoensis, but stimulated starch accumulation in the cytoplasm through feedback to the photorespiration pathway and PP pathway to replenish intermediates for the Calvin cycle. This study is the first to explore the specific function of chloroplast CA in intertidal macroalgae using genomic technology. The results provide valuable insights into the adaption mechanisms of intertidal macroalgae to their environment.
COATi: statistical pairwise alignment of protein-coding sequences
Authors: García Mesa Juan J. , Zhu Ziqi , Cartwright Reed A. 
Published: May 2023

AbstractSequence alignment is an essential method in bioinformatics and the basis of many analyses, including phylogenetic inference, ancestral sequence reconstruction, and gene annotation. Sequence artifacts and errors made during alignment reconstruction can impact downstream analyses leading to erroneous conclusions in comparative and functional genomic studies. For example, abiological frameshifts and early stop codons are common artifacts found in protein coding sequences that have been annotated in reference genomes. While such errors are eventually fixed in the reference genomes of model organisms, many genomes used by researchers contain these artifacts, and researchers often discard large amounts of data in comparative genomic studies to prevent artifacts from impacting results. To address this need, we present COATi, a statistical, codon-aware pairwise aligner that supports complex insertion-deletion models and can handle artifacts present in genomic data. COATi allows users to reduce the amount of discarded data while generating more accurate sequence alignments.
Wired together, change together: Spike timing modifies transmission in converging assemblies
Authors: Spivak Lidor , Someck Shirly , Levi Amir , Sivroni Shir , Stark Eran 
Published: May 2023

AbstractPrecise timing of neuronal spikes may lead to changes in synaptic connectivity and is thought to be crucial for learning and memory. However, the effect of spike timing on neuronal connectivity in the intact brain remains unknown. Using closed-loop optogenetic stimulation in CA1 of freely-moving mice, we generated new spike patterns between presynaptic pyramidal cells (PYRs) and postsynaptic parvalbumin-immunoreactive (PV) cells. This stimulation led to spike transmission changes which occurred together across all presynaptic PYRs connected to the same postsynaptic PV cell. The precise timing of all presynaptic and postsynaptic cells spikes impacted transmission changes. These findings reveal an unexpected plasticity mechanism, wherein spike timing of a whole cell assembly has a more substantial impact on effective connectivity than that of individual cell pairs.
Improving malaria case management with artemisinin-based combination therapies and malaria rapid diagnostic tests in private medicine retail outlets in sub-Saharan Africa: a systematic review
Authors: Goodman Catherine , Tougher Sarah , Shang Terrissa Jing , Visser Theodoor 
Published: May 2023

AbstractPrivate medicine retailers (PMRs) such as pharmacies and drug stores account for a substantial share of treatment-seeking for fever and malaria, but there are widespread concerns about quality of care, including inadequate access to malaria rapid diagnostic tests (RDTs) and artemisinin-based combination therapies (ACTs). This review synthesizes evidence on the effectiveness of interventions to improve malaria case management in PMRs in sub-Saharan Africa (PROSPERO #2021:CRD42021253564). We included quantitative studies evaluating interventions supporting RDT and/or ACT sales by PMR staff, with a historical or contemporaneous control group, and outcomes related to care received. We searched Medline Ovid, Embase Ovid, Global Health Ovid, Econlit Ovid and the Cochrane Library; unpublished studies were identified by contacting key informants. We conducted a narrative synthesis by intervention category. We included 41 papers, relating to 34 studies. There was strong evidence that small and large-scale ACT subsidy programmes (without RDTs) increased the market share of quality-assured ACT in PMRs, including among rural and poorer groups, with increases of over 30 percentage points in most settings. Interventions to introduce or enhance RDT use in PMRs led to RDT uptake among febrile clients of over two-thirds and dispensing according to RDT result of over three quarters, though some studies had much poorer results. Introducing Integrated Community Case Management (iCCM) was also effective in improving malaria case management. However, there were no eligible studies on RDT or iCCM implementation at large scale. There was limited evidence that PMR accreditation (without RDTs) increased ACT uptake. Key evidence gaps include evaluations of RDTs and iCCM at large scale, evaluations of interventions including use of digital technologies, and robust studies of accreditation and other broader PMR interventions.
Demographic Consequences of Damage Dynamics in Single-Cell Ageing
Authors: Tuğrul Murat , Steiner Ulrich K 
Published: May 2023

AbstractAgeing is driven by damage accumulation leading to a decline in function over time. In single-cell systems, in addition to this damage accumulation within individuals, asymmetric damage partitioning at cell division can play a crucial role in shaping demographic ageing patterns. Despite empirical single-cell studies providing quantitative data at the molecular and demographic level, a comprehensive theory of how cellular damage production and asymmetric partitioning propagate and influence demographic patterns is still lacking. Here, we present a generic and flexible damage model using a stochastic differential equation approach that incorporates stochastic damage accumulation and asymmetric damage partitioning at cell divisions. We formulate an analytical approximation linking cellular and damage parameters to demographic ageing patterns. Interestingly, the lifespan of cells follows an inverse-gaussian distribution whose underlying properties derive from cellular and damage parameters. We demonstrate how stochasticity (noise) in damage production, asymmetry in damage partitioning, and division frequency shape lifespan distribution. Confronting the model to various empiricalE.colidata reveals non-exponential scaling in mortality rates, a scaling that cannot be captured by classical Gompertz-Makeham models. Our findings provide a deep understanding of how fundamental processes contribute to cellular damage dynamics and generate demographic patterns. Our damage model’s generic nature offers a valuable framework for investigating ageing in diverse biological systems.SignificanceAsymmetries and randomness in cellular events play important roles in establishing the diversity at evolutionary and demographic scales. Looking at single-cells, ageing processes are influenced by stochastic damage accumulation and asymmetric damage partitioning at cell divisions. Utilising stochastic differential equations, we develop a cellular damage model that encapsulate both noisy damage accumulation within cells and asymmetric damage partitioning among cells when they divide. In doing so we bridge molecular stochastic processes, demographic fates of individuals, and population level demographic distributions. Our model aligns with empirical data fromE.colisingle-cell studies and advances our understanding compared to traditional demographic models. The generic and adaptable nature of our model paves the way for broader applications in ageing research across biological systems, highlighting the influences of stochasticity and asymmetry on cellular biology.
Integrating stereotypes and factual evidence in interpersonal communication
Authors: Koch Saskia B. J. , Tyborowska Anna , Niermann Hannah C. M. , Cillessen Antonius H. N. , Roelofs Karin , Bašnáková Jana , Toni Ivan , Stolk Arjen 
Published: May 2023

AbstractStereotypes can exert a powerful influence on our interactions with others, potentially leading to prejudice when factual evidence is ignored. Here, we identify neuroanatomical and developmental factors that influence the real-time integration of stereotypes and factual evidence during live social interactions. The study uses precisely quantified communicative exchanges in a longitudinal cohort of seventeen-year-olds followed since infancy, testing their ability to moderate stereotype tendencies toward children as contrary evidence accumulates. Our results indicate that the impact of stereotypes on communicative behavior is linked to individual variations in gray matter density and cortical thickness in the right anterior cingulate gyrus. In contrast, the ability to moderate stereotype tendencies is influenced by developmental exposure to social interactions during the initial years of life, beyond the effects of familial environment and later experiences. These findings pinpoint a key brain structure underlying stereotype tendencies and suggest that early-life social experiences have lasting consequences on how individuals integrate factual evidence in interpersonal communication.
Demographic consequences of an extreme heatwave are mitigated by spatial heterogeneity in an annual monkeyflower
Authors: McDonald Laura M. , Scharnagl Anna , Turcu Andrea K. , Patterson Courtney M. , Kooyers Nicholas J. 
Published: May 2023

AbstractHeatwaves are becoming more frequent and intense with climate change, but the demographic and evolutionary consequences of heatwaves are rarely investigated in herbaceous plant species. We examine the consequences of a short but extreme heatwave in Oregon populations of the common yellow monkeyflower (Mimulus guttatus) by leveraging a common garden experiment planted with range-wide populations and observational studies of eleven local populations. In the common garden, 89% of seedlings died during the heatwave including >96% of seedlings from geographically-local populations. Some populations from hotter and drier environments had higher fitness, however others from comparable environments performed poorly. Observational studies of local natural populations drastically differed in the consequences of the heatwave - one population was completely extirpated and nearly half had a >50% decrease in fitness. However, a few populations hadgreaterfitness during the heatwave year. Differences in mortality corresponded to the impact of the heatwave on soil moisture – retention of soil moisture throughout the heatwave led to greater survivorship. Our results suggest that not all populations experience the same intensity or degree of mortality during extreme events and such heterogeneity could be important for genetic rescue or to facilitate the distribution of adaptive variants throughout the region.