bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeepLabCut-based Behavioural and Posture Analysis in a Cricket
Authors: Hayakawa Shota , Kataoka Kosuke , Yamamoto Masanobu , Asahi Toru , Suzuki Takeshi 
Published: November 2023

AbstractCircadian rhythms are indispensable intrinsic programs that regulate the daily rhythmicity of physiological processes, such as feeding and sleep. The cricket has been employed as a model organism for understanding the neural mechanisms underlying circadian rhythms in insects. However, previous studies measuring rhythm-controlled behaviours only analysed locomotive activity using seesaw-type and infrared sensor-based actometers. Meanwhile, advances in deep learning techniques have made it possible to analyse animal behaviour and posture using software that is devoid of human bias and does not require physical tagging of individual animals. Here, we present a system that can simultaneously quantify multiple behaviours in individual crickets, such as locomotor activity, feeding, and sleep-like states, in the long-term, using DeepLabCut, a supervised machine learning-based software for body keypoints labeling. Our system successfully labelled the six body parts of a single cricket with a high level of confidence and produced reliable data showing the diurnal rhythms of multiple behaviours. Our system also enabled the estimation of sleep-like states by focusing on posture, instead of immobility time, which is a conventional parameter. We anticipate that this system will provide an opportunity for simultaneous and automatic prediction of cricket behaviour and posture, facilitating the study of circadian rhythms.
Flock response to sustained asynchronous predator attacks
Authors: Mohapatra Siddhant , Mahapatra Pallab Sinha 
Published: November 2023

AbstractCollective behaviour is a ubiquitous emergent phenomenon where organisms share information and conduct complicated manoeuvres as a group. Dilution of predation risk is presumed to be a major proponent contributing towards the emergence of such fascinating behaviour. However, the role of multiple sources of predation risk in determining the characteristics of the escape manoeuvres remains largely unexplored. The current work aims to address this paucity by examining the response of a flock to multiple persistently pursuing predators, using an agent-based approach employing a force-based model. Collective features such as herding, avoiding and split-and-join are observed across a wide spectrum of systemic conditions. The transition from one response state to another is examined as a function of the relative angle of predator attack, a parameter exclusive to multi-predator systems. Other concomitant parameters, such as the frequency of attacks and compatibility of target selection tactics of the predators, have a significant effect on the escape probability of the prey (i.e., the success rate of escape manoeuvres). A quantitative analysis has been carried out to determine the most successful combination of target selection while also focusing on beneficial ancillary effects such as flock splitting. The long-term dynamics of the system indicate a faster decay of prey numbers (higher prey mortality) at higher coordination strength due to a monotonically decreasing relation between coordination strength and prey speed supplanted by coincidental synchrony of predator attacks. The work highlights the non-additive nature of the effects of predation in a multi-predator system and urges further scrutiny of group hunting dynamics in such systems.Author summaryCollective motion is a natural phenomenon observed across a wide range of length and time scales. One purported reason for the development of such behaviour is to reduce the individual risk of predation through the many-eyes effect and group manoeuvring in case of attacks. However, the behaviour of the prey flock can turn out to be starkly different when there are multiple predators involved. We examine the response of the flock in the presence of multiple predators and find the circumstances leading to the occurrence of different escape manoeuvres. We observe the stricter penalty warranted on the flock due to certain manoeuvres, such as split-and-join, due to the asynchronous and persistent nature of the predator attacks. We also identify the issues with superfluous coordination among prey and its ramifications in terms of prey mortality. The combined effect of the predators is found to outpace the sum of individual predator prowess. The current work emphasises the distinct dynamics of a multi-predator system and puts forth pertinent queries regarding synchronisation among predators and group hunting tactics.
Does cardiorespiratory fitness mediate or moderate the association between mid-life physical activity and cognitive function? Findings from the 1958 British birth cohort study
Authors: Norris Tom , Mitchell John J , Blodgett Joanna M , Pinto Pereira Mark Snehal M 
Published: November 2023

AbstractBackgroundPhysical activity (PA) is associated with a lower risk of cognitive decline and all-cause dementia in later life. Pathways underpinning this association are unclear but may involve either mediation and/or moderation by cardiorespiratory fitness (CRF).MethodsData on participation in PA (exposure) at 42y, non-exercise testing CRF (NETCRF, mediator/moderator) at 45y and overall cognitive function (outcome) at 50y were obtained from 9,385 participants in the 1958 British birth cohort study. We used a four-way decomposition approach to examine the relative contributions of mediation and moderation by NETCRF on the association between PA at 42y and overall cognitive function at 50y.ResultsIn males, the estimated overall effect of 42y PA ≥once per week (vs. <once per week) was a 0.08 (95% confidence interval: 0.04,0.13) higher overall cognitive function z-score at 50y. The estimated controlled direct effect was similar (0.08 (0.03, 0.12)). Thus, the proportion of the estimated effect via mediation or moderation by NETCRF was small (∼3%), with confidence intervals straddling the null. In females, there was no estimated overall effect of PA on overall cognitive function.ConclusionWe present the first evidence from a four-way decomposition analysis of the potential contribution that CRF plays in the relationship between mid-life PA and subsequent cognitive function. Our lack of evidence in support of CRF mediating or moderating the PA―cognitive function association suggests that other pathways underpin this association.
Benchmarking multi-omics integration algorithms across single-cell RNA and ATAC data
Authors: Xiao Chuxi , Chen Yixin , Wei Lei , Zhang Xuegong 
Published: November 2023

AbstractRecent advancements in single-cell sequencing technologies have generated extensive omics data in various modalities and revolutionized cell research, especially in the single cell RNA and ATAC data. The joint analysis across scRNA-seq data and scATAC-seq data has paved the way to comprehending the cellular heterogeneity and complex cellular regulatory networks. Multi-omics integration is gaining attention as an important step in joint analysis, and the number of computational tools in this field is growing rapidly. In this paper, we benchmarked 12 multi-omics integration methods on three integration tasks via qualitative visualization and quantitative metrics, considering six main aspects that matter in multi-omics data analysis. Overall, we found that different methods have their own advantages on different aspects, while some methods outperformed other methods in most aspects. We therefore provided guidelines for selecting appropriate methods for specific scenarios and tasks to help obtain meaningful insights from multi-omics data integration.
Distinct mechanisms of plant immune resilience revealed by natural variation in warm temperature-modulated disease resistance amongArabidopsisaccessions
Authors: Rossi Christina A. M. , Patel Dhrashti N. , Castroverde Christian Danve M. 
Published: November 2023

AbstractElevated temperature suppresses production of the key plant defence hormone salicylic acid (SA). Heat-mediated SA suppression and resulting plant vulnerability are due to downregulated expression ofCALMODULIN BINDING PROTEIN 60-LIKE G(CBP60g) andSYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1(SARD1), which encode master regulators of plant immunity. However, previous studies inArabidopsis thalianaplants have primarily focused on the accession Columbia-0 (Col-0), while the mechanisms governing the intraspecific variation inArabidopsisimmunity under elevated temperature have remained unknown. Here we show that BASIC HELIX LOOP HELIX 059 (bHLH059), a thermosensitive SA regulator at non-stress temperatures, does not regulate immune suppression under warmer temperatures. In agreement, temperature-resilient and -sensitiveArabidopsisaccessions based on disease resistance to the bacterial pathogenPseudomonas syringaepv.tomato(Pst) DC3000 did not correlate withbHLH059sequence polymorphisms. Instead, we found that different temperature-resilient accessions exhibit varyingCBP60gandSARD1expression profiles, potentially revealing bothCBP60g/SARD1-dependent and independent mechanisms of plant immune resilience to warming temperature. Collectively, this study has unveiled the intraspecific diversity ofArabidopsisimmune responses under warm temperatures. Our dissection of mechanisms underlying temperature-modulated plant immunity could aid in predicting plant responses to climate change and provide foundational knowledge for climate-resilient crop engineering.
Centrifuger: lossless compression of microbial genomes for efficient and accurate metagenomic sequence classification
Authors: Song Li , Langmead Ben 
Published: November 2023

AbstractCentrifuger is an efficient taxonomic classification method that compares sequencing reads against a microbial genome database. In Centrifuger, the Burrows-Wheeler transformed genome sequences are losslessly compressed using a novel scheme called run-block compression. Run-block compression achieves sublinear space complexity and is effective at compressing diverse microbial databases like RefSeq while supporting fast rank queries. Combining this compression method with other strategies for compacting the Ferragina-Manzini (FM) index, Centrifuger reduces the memory footprint by half compared to other FM-index-based approaches. Furthermore, the lossless compression and the unconstrained match length help Centrifuger achieve greater accuracy than competing methods at lower taxonomic levels.
Epigenetic heritability of cell plasticity drives cancer drug resistance through one-to-many genotype to phenotype mapping
Authors: Oliveira Erica , Milite Salvatore , Fernandez-Mateos Javier , Cresswell George D , Yara-Romero Erika , Vlachogiannis Georgios , Chen Bingjie , James Chela , Patruno Lucrezia , Ascolani Gianluca , Acar Ahmet , Heide Timon , Spiteri Inma , Graudenzi Alex , Caravagna Giulio , Bertotti Andrea , Graham Trevor A , Magnani Luca , Valeri Nicola , Sottoriva Andrea 
Published: November 2023

AbstractCancer drug resistance is multi-factorial, driven by heritable (epi)genetic changes but also phenotypic plasticity. Here we dissect it by perturbing colorectal cancer patient-derived organoids longitudinally with drugs in sequence. Combining longitudinal tracking, single cell ’omics, evolutionary modelling, and machine leaning, we found that different targeted drugs select for distinct subclones, supporting rationally designed drug sequences. The cellular memory was encoded as a heritable epigenetic configuration, from which multiple transcriptional programmes could run, supporting a one-to-many (epi)genotype-to- phenotype map that explains how clonal expansions and plasticity manifest together. This may ensure drug resistance subclones can exhibit distinct phenotypes in changing environments while still preserving the cellular memory encoding for their selective advantage. Chemotherapies resistance was instead entirely driven by plasticity. Inducing further chromosomal instability before drug application changed clonal evolution but not convergent transcriptional programmes. Collectively, our data show how genetic and epigenetic alterations are selected to “permissive epigenome” enabling phenotypic plasticity.
Contrasting patterns of water use efficiency and annual radial growth among European beech forests along the Italian peninsula
Authors: Puchi Paulina F. , Dalmonech Daniela , Vangi Elia , Battipaglia Giovanna , Tognetti Roberto , Collalti Alessio 
Published: November 2023

SummaryTree mortality and forest dieback episodes are increasing due to drought and heat stress. Nevertheless, a comprehensive understanding of mechanisms enabling trees to withstand and survive droughts remains lacking. Our study investigated basal area increment (BAI), and δ13C- derived intrinsic water-use-efficiency (iWUE), to elucidate beech resilience across four healthy stands in Italy with varying climates and water availability. Additionally, fist-order autocorrelation (AR1) analysis was performed to detect early warning signals for potential tree dieback risks during extreme drought events.Results reveal a negative link between BAI and vapour pressure deficit (VPD), especially in southern latitudes. After the 2003 drought, BAI decreased at the northern site, with an increase in δ13C andiWUE, indicating conservative water-use. Conversely, the southern sites showed increased BAI andiWUE, likely influenced by rising CO2and improved water availability. In contrast, the central site sustained higher transpiration rates due to higher soil water holding capacity (SWHC). Despite varied responses, most sites exhibited reduced resilience to future extreme events, indicated by increased AR1.Temperature significantly affected beechiWUE and BAI in northern Italy, while VPD strongly influenced the southern latitudes. The observed increase in BAI andiWUE in southern regions might be attributed to an acclimation response.
Decoil: Reconstructing extrachromosomal DNA structural heterogeneity from long-read sequencing data
Authors: Giurgiu Mădălina , Wittstruck Nadine , Rodriguez-Fos Elias , González Rocío Chamorro , Brückner Lotte , Krienelke-Szymansky Annabell , Helmsauer Konstantin , Hartebrodt Anne , Euskirchen Philipp , Koche Richard P. , Haase Kerstin , Reinert Knut , Henssen Anton G. 
Published: November 2023

AbstractCircular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. EcDNA can be structurally complex and contain rearranged DNA sequences derived from multiple chromosome locations. As the structure of ecDNA can impact oncogene regulation and may indicate mechanisms of its formation, disentangling it at high resolution from sequencing data is essential. Even though methods have been developed to identify and reconstruct ecDNA in cancer genome sequencing, it remains challenging to resolve complex ecDNA structures, in particular amplicons with shared genomic footprints. We here introduce Decoil, a computational method which combines a breakpoint-graph approach withLASSOregression to reconstruct complex ecDNA and deconvolve co-occurring ecDNA elements with overlapping genomic footprints from long-read nanopore sequencing. Decoil outperformsde-novoassembly and alignment-based methods in simulated longread sequencing data for both simple and complex ecDNAs. Applying Decoil on whole genome sequencing data uncovered different ecDNA topologies and explored ecDNA structure heterogeneity in neuroblastoma tumors and cell lines, indicating that this method may improve ecDNA structural analyzes in cancer.
High-throughput profiling of metabolic responses to exogenous nutrients inSynechocystissp. PCC 6803
Authors: Haavisto Vilhelmiina , Landry Zachary , Pontrelli Sammy 
Published: November 2023

AbstractCyanobacteria fix carbon dioxide and release carbon-containing compounds into the wider ecosystem, yet they are sensitive to small metabolites that may impact their growth and physiology. Several cyanobacteria can grow mixotrophically, but we currently lack a molecular understanding of how specific nutrients may alter the compounds they release, limiting our knowledge of how environmental factors might impact primary producers and the ecosystems they support. In this study, we develop a high-throughput phytoplankton culturing platform and identify how the model cyanobacteriumSynechocystis sp.PCC 6803 responds to nutrient supplementation. We assess growth responses to 32 nutrients at two concentrations, identifying 15 that are utilized mixotrophically. Seven nutrient sources significantly enhance growth, while 19 elicit negative growth responses at one or both concentrations. High-throughput exometabolomics indicates that oxidative stress limits PCC 6803’s growth, but may be alleviated by antioxidant metabolites. Furthermore, glucose and valine induce strong changes in metabolite exudation in a possible effort to correct pathway imbalances or maintain intracellular elemental ratios. This study sheds light on the flexibility and limits of cyanobacterial physiology and metabolism, as well as how primary production and trophic food webs may be modulated by exogenous nutrients.ImportanceCyanobacteria capture and release carbon compounds to fuel microbial food webs, yet we lack a comprehensive understanding of how external nutrients modify their behavior and what they produce. We developed a high throughput culturing platform to evaluate how the model cyanobacteriumSynechocystis sp.PCC 6803 responds to a broad panel of externally supplied nutrients. We found that growth may be enhanced by metabolites that protect against oxidative stress, and that growth and exudate profiles are altered by metabolites that interfere with central carbon metabolism and elemental ratios. This work contributes a holistic perspective of the versatile response of PCC 6803 to externally supplied nutrients, which may alter carbon flux into the wider ecosystem.
Hot springs viruses at Yellowstone National Park have ancient origins and are adapted to their thermophilic hosts
Authors: Benites L. Felipe , Stephens Timothy G. , Van Etten Julia , James Timeeka , Christian William C. , Barry Kerrie , Grigoriev Igor V. , McDermott Timothy R. , Bhattacharya Debashish 
Published: November 2023

AbstractGeothermal springs in areas such as Yellowstone National Park (YNP), USA house unicellular red algae that dominate the microbial biomass. Little is known about the viruses that infect the biota. Here we used metagenomics to characterize the multi-kingdom infecting virus community associated with red algal mats in three neighboring habitats (creek, endolithic, soil) at Lemonade Creek, YNP to determine their taxonomic composition, predicted gene functions, extent of horizontal gene transfer, and potential links to hosts. We find that despite proximity, each habitat houses a unique collection of viruses, with the giant viruses, Megaviricetes, dominant in all three. The early branching phylogenetic position of genes encoded on metagenome assembled virus genomes (vMAGs) suggests that the YNP lineages are of ancient origins and not the result of multiple invasions from mesophilic habitats. The existence of genomic footprints of adaptation to thermophily in the vMAGs is consistent with this idea. Our study is the first analysis of viruses associated with polyextremophilic red algae that form extensive microbial mats in YNP and are common worldwide at geothermal sites. Although more recent than the earliest forms of prokaryotic life, these eukaryotic algal mats originated ca. 1.5 Bya, and therefore span a significant period of the planet’s history. Our data are therefore relevant to understanding biotic interactions on the early Earth.
Chronic activation of a negative engram induces behavioral and cellular abnormalities
Authors: Jellinger Alexandra L. , Suthard Rebecca L. , Yuan Bingbing , Surets Michelle , Ruesch Evan A. , Caban Albit J. , Liu Shawn , Shpokayte Monika , Ramirez Steve 
Published: November 2023

AbstractNegative memories engage a brain and body-wide stress response in humans that can alter cognition and behavior. Prolonged stress responses induce maladaptive cellular, circuit, and systems-level changes that can lead to pathological brain states and corresponding disorders in which mood and memory are affected. However, it’s unclear if repeated activation of cells processing negative memories induces similar phenotypes in mice. In this study, we used an activity-dependent tagging method to access neuronal ensembles and assess their molecular characteristics. Sequencing memory engrams in mice revealed that positive (male-to-female exposure) and negative (foot shock) cells upregulated genes linked to anti- and pro-inflammatory responses, respectively. To investigate the impact of persistent activation of negative engrams, we chemogenetically activated them in the ventral hippocampus over three months and conducted anxiety and memory-related tests. Negative engram activation increased anxiety behaviors in both 6- and 14-month-old mice, reduced spatial working memory in older mice, impaired fear extinction in younger mice, and heightened fear generalization in both age groups. Immunohistochemistry revealed changes in microglial and astrocytic structure and number in the hippocampus. In summary, repeated activation of negative memories induces lasting cellular and behavioral abnormalities in mice, offering insights into the negative effects of chronic negative thinking-like behaviors on human health.
The MYC axis in advanced prostate cancer is impacted through concurrent targeting of ERβ and AR using a novel ERβ-selective ligand alongside Enzalutamide
Authors: Gray Jaimie S. , Wani Sajad A. , Hussain Shahid , Huang Phoebe , Nayak Debasis , Long Mark D. , Yates Clayton , Clinton Steven K. , Bennet Chad E. , Coss Christopher C. , Campbell Moray J. 
Published: November 2023

ABSTRACTWe have dissected the role of Estrogen receptor beta (ERβ) in prostate cancer (PCa) with a novel ERβ ligand, OSU-ERb-12. Drug screens revealed additive interactions between OSU-ERB-12 and either epigenetic inhibitors or the androgen receptor antagonist, Enzalutamide (Enza). Clonogenic and cell biolody studies supported the potent additive effects of OSU-ERB-12 (100nM) and Enza (1µM). The cooperative behavior was in PCa cell lines treated with either OSU- ERB-12 plus Enza or combinations involving 17β-estradiol (E2). OSU-ERb-12 plus Enza uniquely impacted the transcriptiome, accessible chromatin, and the AR, MYC and H3K27ac cistromes. This included skewed transcriptional responses including suppression of the androgen and MYC transcriptomes, and repressed MYC protein. OSU-ERb-12 plus Enza uniquely impacted chromatin accessibility at approximately 3000 nucleosome-free sites, enriched at enhancers, enriched for basic Helix-Loop-Helix motifs. CUT&RUN experiments revealed combination treatment targeting of MYC, AR, and H3K27ac again shaping enhancer accessibility. Specifically, it repressed MYC interactions at enhancer regions enriched for bHLH motifs, and overlapped with publicly-available bHLH cistromes. Finally, cistrome-transcriptome analyses identified ∼200 genes that distinguished advanced PCa tumors in the SU2C cohort with high androgen and low neuroendocrine scores.Statement of ImplicationTargeting ERβ has potentially to augment AR antagonism to restrain MYC signaling and limit growth of advanced prostate cancer.