Organizational Scale Research Articles

Systematic analysis identifies a connection between spatial and genomic variations of chromatin states.

Chromatin states play important roles in the maintenance of cell identities, yet their spatial patterns remain poorly characterized at the organism scale. We developed a systematic approach to analyzing spatial epigenomic data and then applied it to a recently published spatial-CUT&Tag dataset that was obtained from a mouse embryo. We identified a set of spatial genes whose H3K4me3 patterns delineate tissue boundaries. These genes are enriched with tissue-specific transcription factors, and their corresponding genomic loci are marked by broad H3K4me3 domains. Integrative analysis with H3K27me3 profiles showed coordinated spatial transitions across tissue boundaries, which is marked by the continuous shortening of H3K4me3 domains and expansion of H3K27me3 domains. Motif-based analysis identified transcription factors whose activities change significantly during such transitions. Taken together, our systematic analyses reveal a strong connection between the genomic and spatial variations of chromatin states. A record of this paper's transparent peer review process is included in the supplemental information.

Dynamic Tracking of Biological Processes Using Near-Infrared Fluorescent Single-Walled Carbon Nanotubes.

Biological processes are characterized by dynamic and elaborate temporal patterns driven by the interplay of genes, proteins, and cellular components that are crucial for adaptation to changing environments. This complexity spans from molecular to organismal scales, necessitating their real-time monitoring and tracking to unravel the active processes that fuel living systems and enable early disease detection, personalized medicine, and drug development. Single-walled carbon nanotubes (SWCNTs), with their unique physicochemical and optical properties, have emerged as promising tools for real-time tracking of such processes. This perspective highlights the key properties of SWCNTs that make them ideal for such monitoring. Subsequently, it surveys studies utilizing SWCNTs to track dynamic biological phenomena across hierarchical levels─from molecules to cells, tissues, organs, and whole organisms─acknowledging their pivotal role in advancing this field. Finally, the review outlines challenges and future directions, aiming to expand the frontier of real-time biological monitoring using SWCNTs, contributing to deeper insights and novel applications in biomedicine.

THE ROLE OF A HEALTHY LIFESTYLE IN MODERN NATIONAL EDUCATION

The description of a healthy lifestyle is provided in this scientifically grounded article. The sophisticated concepts of global civilizations are organized in this way. The adolescent stage is discussed, and the scientific definition of the importance of aesthetic values in the development of a healthy lifestyle is provided. The role of a healthy lifestyle in national education today was established, the content of its implementation in the educational process was created, and its effectiveness was confirmed in practical and experimental work based on the analysis of indicators of the World Health Organization's scale (WHOQOL-BREF) KAZ. Teenagers comprehend the concept of a healthy lifestyle and accurately assess its social value, which presents an opportunity to form individuals with the proper attitude toward a healthy lifestyle, strong health, beautiful soul, body, and work; In the historical evolution of human development, the concept of health and aesthetic values in the works of great scholars and educators, public figures, and the works of modern scientists are systematized and classified according to educational opportunities;the significance and necessity of aesthetic values for a proper and healthy life of teenagers is more widely propagated and implemented in the content of educational activities of the school; determined the content and system of forming a healthy lifestyle on the basis of aesthetic values through the possibilities of educational activities of the educational process at the main stage of the general education school, and scientifically differentiated the problem of its implementation. It is explained that it is possible to change the inner worldview of students, to educate a person who can deeply understand and maintain a healthy lifestyle.

Multiplex Profiling of miR-122 for Preclinical and Clinical Evaluation of Drug-Induced Liver Injury by a Full-Scale Platform.

Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence in situ hybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.

Cellular sex throughout the organism underlies somatic sexual differentiation

Sex chromosomes underlie the development of male or female sex organs across species. While systemic signals derived from sex organs prominently contribute to sex-linked differences, it is unclear whether the intrinsic presence of sex chromosomes in somatic tissues has a specific function. Here, we use genetic tools to show that cellular sex is crucial for sexual differentiation throughout the body in Drosophila melanogaster. We reveal that every somatic cell converts the intrinsic presence of sex chromosomes into the active production of a sex determinant, a female specific serine- and arginine-rich (SR) splicing factor. This discovery dismisses the mosaic model which posits that only a subset of cells has the potential to sexually differentiate. Using cell-specific sex reversals, we show that this prevalence of cellular sex drives sex differences in organ size and body weight and is essential for fecundity. These findings demonstrate that cellular sex drives differentiation programs at an organismal scale and highlight the importance of cellular sex pathways in sex trait evolution.

Appendage-resident epithelial cells expedite wound healing response in adult zebrafish

Adult zebrafish are able to heal large-sized cutaneous wounds in hours with little to no scarring. This rapid re-epithelialization is crucial for preventing infection and jumpstarting the subsequent regeneration of damaged tissues. Despite significant progress in understanding this process, it remains unclear how vast numbers of epithelial cells are orchestrated on an organismic scale to ensure the timely closure of millimeter-sized wounds. Here, we report an unexpected role of adult zebrafish appendages (fins) in accelerating the re-epithelialization process. Through whole-body monitoring of single-cell dynamics in live animals, we found that fin-resident epithelial cells (FECs) are highly mobile and migrate to cover wounds in nearby body regions. Upon injury, FECs readily undergo organ-level mobilization, allowing for coverage of body surfaces of up to 4.78mm2 in less than 8 h. Intriguingly, long-term fate-tracking experiments revealed that the migratory FECs are not short-lived at the wound site; instead, the cells can persist on the body surface for more than a year. Our experiments on "fin-less" and "fin-gaining" individuals demonstrated that the fin structures are not only capable of promoting rapid re-epithelialization but are also necessary for the process. We further found that fin-enriched extracellular matrix laminins promote the active migration of FECs by facilitating lamellipodia formation. These findings lead us to conclude that appendage structures in regenerative vertebrates, such as fins, may possess a previously unrecognized function beyond serving as locomotor organs. The appendages may also act as a massive reservoir of healing cells, which speed up wound closure and tissue repair.

Global epistasis and the emergence of function in microbial consortia

The many functions of microbial communities emerge from a complex web of interactions between organisms and their environment. This poses a significant obstacle to engineering microbial consortia, hindering our ability to harness the potential of microorganisms for biotechnological applications. In this study, we demonstrate that the collective effect of ecological interactions between microbes in a community can be captured by simple statistical models that predict how adding a new species to a community will affect its function. These predictive models mirror the patterns of global epistasis reported in genetics, and they can be quantitatively interpreted in terms of pairwise interactions between community members. Our results illuminate an unexplored path to quantitatively predicting the function of microbial consortia from their composition, paving the way to optimizing desirable community properties and bringing the tasks of predicting biological function at the genetic, organismal, and ecological scales under the same quantitative formalism.

Current honey bee stressor investigations and mitigation methods in the United States and Canada.

Honey bees are the most important managed insect pollinators in the US and Canadian crop systems. However, the annual mortality of colonies in the past 15 years has been consistently higher than historical records. Because they are eusocial generalist pollinators and amenable to management, honey bees provide a unique opportunity to investigate a wide range of questions at molecular, organismal, and ecological scales. Here, the American Association of Professional Apiculturists (AAPA) and the Canadian Association of Professional Apiculturists (CAPA) created 2 collections of articles featuring investigations on micro and macro aspects of honey bee health, sociobiology, and management showcasing new applied research from diverse groups studying honey bees (Apis mellifera) in the United States and Canada. Research presented in this special issue includes examinations of abiotic and biotic stressors of honey bees, and evaluations and introductions of various stress mitigation measures that may be valuable to both scientists and the beekeeping community. These investigations from throughout the United States and Canada showcase the wide breadth of current work done and point out areas that need further research.

Business strategy of for-profit-oriented sports enterprises in Hungary

AbstractMany sports organisations operate as non-profits, but the emphasis and role of for-profits in this sector cannot be avoided. Today, sports activities are connected to the business sector and generate profit, hence, sports sector is a decisive part of the economy. Sport profile companies differ in their organisational strategy formulation approach. The main focus was to learn more about their strategy approach and market behaviour. 350 sports business organisations were involved in a survey of 3,248 companies, and the Chi-square test, variance analysis, and principal component analysis were applied to the sample. Results showed that 75.7% of the responding sports companies had no written strategic plan. The availability of written strategies seemed to depend on the organisation's scale. The market-following behaviour was confirmed in the case of smaller sports enterprises. Fitness service providers appeared to follow a market-leading behaviour. Growth, investment, and development naturally emerged as essential factors for companies with higher sales revenue and operating sports facilities, and they were relatively less important in sports goods production and trade. Most of the results showed that in the sports business sector, large-scale organisations focus on strategic-related issues more than other players in the industry.

Cross-validation of chemical and genetic disruption approaches to inform host cellular effects on Wolbachia abundance in Drosophila.

Endosymbiotic Wolbachia bacteria are widespread in nature, present in half of all insect species. The success of Wolbachia is supported by a commensal lifestyle. Unlike bacterial pathogens that overreplicate and harm host cells, Wolbachia infections have a relatively innocuous intracellular lifestyle. This raises important questions about how Wolbachia infection is regulated. Little is known about how Wolbachia abundance is controlled at an organismal scale. This study demonstrates methodology for rigorous identification of cellular processes that affect whole-body Wolbachia abundance, as indicated by absolute counts of the Wolbachia surface protein (wsp) gene. Candidate pathways, associated with well-described infection scenarios, were identified. Wolbachia-infected fruit flies were exposed to small molecule inhibitors known for targeting those same pathways. Sequential tests in D. melanogaster and D. simulans yielded a subset of chemical inhibitors that significantly affected whole-body Wolbachia abundance, including the Wnt pathway disruptor, IWR-1 and the mTOR pathway inhibitor, Rapamycin. The implicated pathways were genetically retested for effects in D. melanogaster, using inducible RNAi expression driven by constitutive as well as chemically-induced somatic GAL4 expression. Genetic disruptions of armadillo, tor, and ATG6 significantly affected whole-body Wolbachia abundance. As such, the data corroborate reagent targeting and pathway relevance to whole-body Wolbachia infection. The results also implicate Wnt and mTOR regulation of autophagy as important for regulation of Wolbachia titer.

SARS-CoV-2 rapidly evolves lineage-specific phenotypic differences when passaged repeatedly in immune-naïve mice

The persistence of SARS-CoV-2 despite the development of vaccines and a degree of herd immunity is partly due to viral evolution reducing vaccine and treatment efficacy. Serial infections of wild-type (WT) SARS-CoV-2 in Balb/c mice yield mouse-adapted strains with greater infectivity and mortality. We investigate if passaging unmodified B.1.351 (Beta) and B.1.617.2 (Delta) 20 times in K18-ACE2 mice, expressing the human ACE2 receptor, in a BSL-3 laboratory without selective pressures, drives human health-relevant evolution and if evolution is lineage-dependent. Late-passage virus causes more severe disease, at organism and lung tissue scales, with late-passage Delta demonstrating antibody resistance and interferon suppression. This resistance co-occurs with a de novo spike S371F mutation, linked with both traits. S371F, an Omicron-characteristic mutation, is co-inherited at times with spike E1182G per Nanopore sequencing, existing in different within-sample viral variants at others. Both S371F and E1182G are linked to mammalian GOLGA7 and ZDHHC5 interactions, which mediate viral-cell entry and antiviral response. This study demonstrates SARS-CoV-2’s tendency to evolve with phenotypic consequences, its evolution varying by lineage, and suggests non-dominant quasi-species contribution.

Tracking early mammalian organogenesis - prediction and validation of differentiation trajectories at whole organism scale.

Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 in 6-h intervals and combined this new dataset with our previous atlas (E6.5-E8.5) to produce a densely sampled timecourse of >400,000 cells from early gastrulation to organogenesis. Computational lineage reconstruction identified complex waves of blood and endothelial development, including a new programme for somite-derived endothelium. We also dissected the E7.5 primitive streak into four adjacent regions, performed scRNA-seq and predicted cell fates computationally. Finally, we defined developmental state/fate relationships by combining orthotopic grafting, microscopic analysis and scRNA-seq to transcriptionally determine cell fates of grafted primitive streak regions after 24 h of in vitro embryo culture. Experimentally determined fate outcomes were in good agreement with computationally predicted fates, demonstrating how classical grafting experiments can be revisited to establish high-resolution cell state/fate relationships. Such interdisciplinary approaches will benefit future studies in developmental biology and guide the in vitro production of cells for organ regeneration and repair.

19th International Xenopus Conference Meeting Report: Latest developments and future perspectives.

The African clawed frog, Xenopus laevis, and the Western clawed frog, Xenopus tropicalis, have been foundational model organisms for establishing key principles of embryonic development. Today, the utility of Xenopus has been greatly expanded for studying a wide range of biological processes both in health and disease. Here, we describe the latest advancements from the Xenopus community, which span the molecular, cellular, tissue, and organismal scales.

Self-assembled active actomyosin gels spontaneously curve and wrinkle similar to biological cells and tissues.

Living systems adopt a diversity of curved and highly dynamic shapes. These diverse morphologies appear on many length scales, from cells to tissues and organismal scales. The common driving force for these dynamic shape changes are contractile stresses generated by myosin motors in the cell cytoskeleton, that converts chemical energy into mechanical work. A good understanding of how contractile stresses in the cytoskeleton arise into different three-dimensional (3D) shapes and what are the shape selection rules that determine their final configurations is still lacking. To obtain insight into the relevant physical mechanisms, we recreate the actomyosin cytoskeleton in vitro, with precisely controlled composition and initial geometry. A set of actomyosin gel discs, intrinsically identical but of variable initial geometry, dynamically self-organize into a family of 3D shapes, such as domes and wrinkled shapes, without the need for specific preprogramming or additional regulation. Shape deformation is driven by the spontaneous emergence of stress gradients driven by myosin and is encoded in the initial disc radius to thickness aspect ratio, which may indicate shaping scalability. Our results suggest that while the dynamical pathways may depend on the detailed interactions between the different microscopic components within the gel, the final selected shapes obey the general theory of elastic deformations of thin sheets. Altogether, our results emphasize the importance for the emergence of active stress gradients for buckling-driven shape deformations and provide insights on the mechanically induced spontaneous shape transitions in contractile active matter, revealing potential shared mechanisms with living systems across scales.

A roadmap for pyrodiversity science

AbstractBackgroundContemporary and projected shifts in global fire regimes highlight the importance of understanding how fire affects ecosystem function and biodiversity across taxa and geographies. Pyrodiversity, or heterogeneity in fire history, is often an important driver of biodiversity, though it has been largely overlooked until relatively recently. In this paper, we synthesise previous research to develop a theoretical framework on pyrodiversity–biodiversity relationships and propose future research and conservation management directions.Theoretical FrameworkPyrodiversity may affect biodiversity by diversifying available ecological niches, stabilising community networks and/or supporting diverse species pools available for post‐fire colonisation. Further, pyrodiversity's effects on biodiversity vary across different spatial, temporal and organismal scales depending on the mobility and other life history traits of the organisms in question and may be mediated by regional eco‐evolutionary factors such as historical fire regimes. Developing a generalisable understanding of pyrodiversity effects on biodiversity has been challenging, in part because pyrodiversity can be quantified in various ways.Applying the Pyrodiversity ConceptExclusion of Indigenous fire stewardship, fire suppression, increased unplanned ignitions and climate change have led to dramatic shifts in fire regimes globally. Such shifts include departures from historic levels of pyrodiversity and add to existing challenges to biodiversity conservation in fire‐prone landscapes. Managers navigating these challenges can be aided by targeted research into observed contemporary pyrodiversity–biodiversity relationships as well as knowledge of historical reference conditions informed by both Indigenous and local ecological knowledge and western science.Future Research DirectionsSeveral promising avenues exist for the advancement of pyrodiversity science to further both theoretical and practical goals. These lines of investigation include but are not limited to (1) testing the increasing variety of pyrodiversity metrics and analytical approaches; (2) assessing the spatial and temporal scale‐dependence of pyrodiversity's influence; (3) reconstructing historical pyrodiversity patterns and developing methods for predicting and/or promoting future pyrodiversity; and (4) expanding the focus of pyrodiversity science beyond biodiversity to better understand its influence on ecosystem function and processes more broadly.

BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.

The evolving history of BRCA1 research demonstrates the profound interconnectedness of a single protein within the web of crucial functions in human cells. Mutations in BRCA1, a tumor suppressor gene, have been linked to heightened breast and ovarian cancer risks. However, despite decades of extensive research, the mechanisms underlying BRCA1's contribution to tissue-specific tumor development remain elusive. Nevertheless, much of the BRCA1 protein's structure, function, and interactions has been elucidated. Individual regions of BRCA1 interact with numerous proteins to play roles in ubiquitination, transcription, cell checkpoints, and DNA damage repair. At a cellular scale, these BRCA1 functions coordinate tumor suppression, R-loop prevention, and cellular differentiation, all of which may contribute to BRCA1's role in cancer tissue specificity. As research on BRCA1 and breast cancer continues to evolve, it will become increasingly evident that modern materials such as Bisphenol A should be examined for their relationship with DNA stability, cancer incidence, and chemotherapy. Overall, this review offers a comprehensive understanding of BRCA1's many roles at a molecular, cellular, organismal, and environmental scale. We hope that the knowledge gathered here highlights both the necessity of BRCA1 research and the potential for novel strategies to prevent and treat cancer in individuals carrying BRCA1 mutations.

A synthesis of the risks of marine light pollution across organismal and ecological scales

Abstract Light pollution is a pervasive global stressor to natural systems. However, due to the proximity of human activities along the coasts and open ocean, light is a pervasive yet commonly overlooked pollutant in many marine habitats. There is a well‐developed body of literature on the visual physiology, behaviour and ecology of many marine taxa, and a re‐evaluation of these data can help inform risks of light pollution to impact marine organisms and ecosystems. This paper identifies key knowledge gaps in the study of marine light pollution ecology and recommends research and management foci for future study. Most work on this pollutant has focused on terrestrial ecosystems and taxa, where experts have learned how anthropogenic light influences behaviour, reproduction cycles and population dynamics. However, light pollution bleeds far beyond the shores, affecting many sensitive ecosystems with light available at unnatural times with varied makeup, such as varying intensities or spectra. This review discusses the current understanding of light dynamics underwater, photoreceptive systems of marine taxa and the documented ecological impacts. This lends a critical basis of understanding for the many gaps in marine light pollution biology. For example, little is known about effects of light on broad groups of marine taxa such as cetaceans, ecosystem‐level effects, or interactive impacts of light and other anthropogenic stressors. Light is a key structuring factor of the marine environment and can therefore elicit immense downstream effects on marine organisms individually, at the population‐ or ecosystem‐level. Light pollution is an urgent concern for marine ecosystems because marine organisms have tight relationships with their natural light environment. As the world moves deeper into the Anthropocene, assessing and mitigating the risks of this pollutant to key environmental and economic marine systems is critical to maintaining a healthy ocean.

Phenomics as an approach to Comparative Developmental Physiology.

The dynamic nature of developing organisms and how they function presents both opportunity and challenge to researchers, with significant advances in understanding possible by adopting innovative approaches to their empirical study. The information content of the phenotype during organismal development is arguably greater than at any other life stage, incorporating change at a broad range of temporal, spatial and functional scales and is of broad relevance to a plethora of research questions. Yet, effectively measuring organismal development, and the ontogeny of physiological regulations and functions, and their responses to the environment, remains a significant challenge. "Phenomics", a global approach to the acquisition of phenotypic data at the scale of the whole organism, is uniquely suited as an approach. In this perspective, we explore the synergies between phenomics and Comparative Developmental Physiology (CDP), a discipline of increasing relevance to understanding sensitivity to drivers of global change. We then identify how organismal development itself provides an excellent model for pushing the boundaries of phenomics, given its inherent complexity, comparably smaller size, relative to adult stages, and the applicability of embryonic development to a broad suite of research questions using a diversity of species. Collection, analysis and interpretation of whole organismal phenotypic data are the largest obstacle to capitalising on phenomics for advancing our understanding of biological systems. We suggest that phenomics within the context of developing organismal form and function could provide an effective scaffold for addressing grand challenges in CDP and phenomics.

Single-molecule imaging of genome maintenance proteins encountering specific DNA sequences and structures

DNA repair pathways are tightly regulated processes that recognize specific hallmarks of DNA damage and coordinate lesion repair through discrete mechanisms, all within the context of a three-dimensional chromatin landscape. Dysregulation or malfunction of any one of the protein constituents in these pathways can contribute to aging and a variety of diseases. While the collective action of these many proteins is what drives DNA repair on the organismal scale, it is the interactions between individual proteins and DNA that facilitate each step of these pathways. In much the same way that ensemble biochemical techniques have characterized the various steps of DNA repair pathways, single-molecule imaging (SMI) approaches zoom in further, characterizing the individual protein-DNA interactions that compose each pathway step. SMI techniques offer the high resolving power needed to characterize the molecular structure and functional dynamics of individual biological interactions on the nanoscale. In this review, we highlight how our lab has used SMI techniques – traditional atomic force microscopy (AFM) imaging in air, high-speed AFM (HS-AFM) in liquids, and the DNA tightrope assay – over the past decade to study protein-nucleic acid interactions involved in DNA repair, mitochondrial DNA replication, and telomere maintenance. We discuss how DNA substrates containing specific DNA sequences or structures that emulate DNA repair intermediates or telomeres were generated and validated. For each highlighted project, we discuss novel findings made possible by the spatial and temporal resolution offered by these SMI techniques and unique DNA substrates.

Three-dimensional flow and turbulence structure around Sea Cucumber Apostichopus japonicus

The sea cucumber Apostichopus japonicus (A. japonicus) is a benthic invertebrate with a quasi-cylindrical body and several rows of papillae (conical prominence) on its body wall. As nutrient recyclers, A. japonicus plays a fundamental role in marine ecosystems and is one of the most important commercial aquaculture species in eastern Asia. Despite its ecological and economical importance, little is known concerning the flow characteristics surrounding A. japonicus on the organism scale. Research on the detailed flow structure at such a scale may serve as a significant step toward understanding the transport of sediment and nutrients in the vicinity of A. japonicus. This study sets up the D3Q27 multiple-relaxation-time lattice Boltzmann method to obtain the three-dimensional flow structure around an individual A. japonicus placed at the bottom of a flat-bed channel. The numerical model is validated by a water flume experiment. The flow patterns exhibit distinctive features at three different angles of attack (0°, 45°, 90°). The increasing inflow velocity (0.1m/s, 0.25m/s, 0.4m/s) brings no fundamental change to the structure of flow fields but induces more small-scale vortices and larger velocity fluctuations. This study investigates the complex turbulent flow fields around the A. japonicus and provides new insight for future studies on the interaction between water flow and A. japonicus.