Biological Innovations Research Articles

Innovations and Future Trends in Storage Pest Management

Current innovations and future trends in storage pest management, with a specific focus on the Indian context. The critical role of effective pest management in agriculture and food security is underscored, considering its impact on economic stability and public health. It begins by detailing the challenges faced in storage pest management, including the variety of pests like insects and rodents, and the damage they inflict on stored agricultural products. It critiques the limitations of traditional pest management methods, particularly chemical control, and highlights emerging issues such as climate change effects and pesticide resistance. The core examines the latest innovations in storage pest management. Advanced chemical approaches like novel pesticides and controlled release formulations are discussed, alongside the rise of nanotechnology applications in pest control, including nano-pesticides and smart delivery systems. The emergence of biological control innovations, particularly new biocontrol agents, and genetic control strategies like the sterile insect technique, marks a significant shift towards more sustainable pest management methods. Additionally, It explores developments in physical and mechanical control methods, emphasizing improved storage facilities and environmental control techniques. Integrated Pest Management (IPM) approaches are identified as a key future trend, promoting holistic and sustainable strategies, with case studies underscoring their success and practical application. It also addresses the vital role of policy and regulatory developments, considering the impact of global regulations and the importance of international cooperation and standards in shaping pest management practices in India. Ethical and environmental considerations form a crucial part of the discourse, focusing on the ecological impact of pest management and the balance between control measures and conservation efforts. It concludes with an examination of practical applications and case studies, providing insights into real-world challenges and the strategies employed to overcome them. Overall, It offers a thorough analysis of the state-of-the-art in storage pest management, highlighting the intersection of innovation, sustainability, and practicality. It aims to provide valuable guidance for researchers, policymakers, and practitioners in the field, contributing to the advancement of more effective, environmentally responsible, and sustainable pest management strategies in India.

Graphene oxide: Synthesis and laser spectroscopy approach

Nanotechnology research offers advancements in materials and industrial uses such as nano-electronics, medical sciences, fuel, biology, and technological innovation. The most often employed nanomaterial is Graphene oxide (GO), which has been regarded as a dominant progenitor for many specialized industries. The current work aims to establish a new, cost-effective, easy, and straightforward GO synthesis method. Laser spectroscopy and even traditional tools have been utilized for characterization. The prepared GO has been confirmed by XRD and FT-IR spectroscopy. Laser spectroscopy based on confocal microscopes like Raman micro-spectroscopy and fluorescence lifetime imaging microscopy (FLIM) has been used to ensure the synthesis of GO. Also, it could help in the detection of the prepared layer thickness. Raman spectroscopy detects the number of GO layers, which is one on average, while the Raman mapping shows a good distribution of GO on the substrate. Based on excitation with a 445 nm pulsed laser, FLIM shows that mono GO layers cover most of the surface while only a tiny area contains more than a single layer. The novel aspect of this work is the method of preparation and the way of utilizing both FLIM and Raman to detect the number of GO layers. The prepared GO could be used in many applications like solar cells and filtration.

Chapter 5: Major Biological Innovations in the History of Life on Earth.

All organisms living on Earth descended from a single, common ancestral population of cells, known as LUCA-the last universal common ancestor. Since its emergence, the diversity and complexity of life have increased dramatically. This chapter focuses on four key biological innovations throughout Earth's history that had a significant impact on the expansion of phylogenetic diversity, organismal complexity, and ecospace habitation. First is the emergence of the last universal common ancestor, LUCA, which laid the foundation for all life-forms on Earth. Second is the evolution of oxygenic photosynthesis, which resulted in global geochemical and biological transformations. Third is the appearance of a new type of cell-the eukaryotic cell-which led to the origin of a new domain of life and the basis for complex multicellularity. Fourth is the multiple independent origins of multicellularity, resulting in the emergence of a new level of complex individuality. A discussion of these four key events will improve our understanding of the intertwined history of our planet and its inhabitants and better inform the extent to which we can expect life at different degrees of diversity and complexity elsewhere.

Analysis of the Development Needs of Student Worksheet Based on Local Wisdom of Biotechnology Material at Senior High School, Kupang City

This study aims to obtain an overview of the formulation of student worksheed (called as LKPD) based on local wisdom that needs to be developed in learning the biology of conventional biotechnology materials at SMA N 5 Kupang City which is adjusted to the learning achievements and objectives. The subjects in this study were 3 teachers who taught in class X of SMAN 5 Kupang City, and 175 students were randomly drawn from all grade X students of science interest at SMA N 5 Kupang City. Research data were collected through interviews and questionnaire dissemination. The research data were analyzed in a qualitative descriptive manner. The results of the study obtained teacher and student responses including students need LKPD based on local wisdom on biotechnology material to make it easier to understand the material, In addition, in learning, teachers provide examples of the results of biotechnology based on local wisdom in the form of pictures and videos, and are presented in the form of virtual laboratories with animations to attract more students' attention, so that students are more motivated to learn which will affect learning outcomes. The biology material for class X semester that is most difficult for students to understand is biological technology innovation material, so teachers need LKPD based on local wisdom in Biotechnology material, which can help students introduce local wisdom in their respective regions so that students can easily apply it in everyday life, and to support learning, which has a positive impact on improving student learning outcomes

Marine redox fluctuations during the Marinoan glaciation

The proliferation of eukaryotes preceding the Cryogenian Marinoan glaciation (650–635 Ma) and the subsequent radiation of early animals imply a conceivable linkage between global glaciation and complex life evolution. However, the marine redox condition remains enigmatic during the Cryogenian, impeding our understanding of the role of O2 on this biological innovation. To fill this gap, we comprehensively reported mineralogy, iron isotope (δ56Fe), and iron speciation in the Cryogenian Nantuo Formation at Liulongshan, South China. This section encompasses glacial marine and non-glacial deposits, where the redbeds situated in the middle of the section, in conjunction with the diamictites adjacent to them, divide the Nantuo Formation into three distinct glacial sedimentary cycles. Micro-particle hematite within the Nantuo Formation indicates that the primary Fe-oxide was authigenic and trapped in water column. Furthermore, the Fe isotopic compositions of these authigenic components (δ56FeHR) calculated by mass balance equation reveal the redox state of the ocean coinciding with dynamic glaciation. The lower diamictite shows an increasing trend of δ56FeHR, Fe/Al, and FeHR/FeT, indicative of gradually more anoxic seawater conditions coupled with ice advance. Although redbeds intervals exhibit higher FeHR/FeT ratios (∼ 0.51), traditionally indicative of anoxic environments, our integration of mineralogical evidence suggested that the increased Feox content in redbeds might represent increased oxidation of Fe(II) at the redox chemocline, rather than the redox conditions of the bottom waters. This interpretation is consistent with the observed decreasing trend in our Fe isotope data, as well as the sedimentological evolution. Subsequently, the positive and increasing δ56FeHR values suggest that the oceanic redox conditions shifted to anoxic as the second glacial episode re-emerged. These findings suggest dynamic fluctuations in the redox condition of the ocean during the Marinoan Ice Age. Specifically, the formation of the redbeds may reflect a locally oxic environment. A modern analogy resembling this situation is blood falls, where the oxidation of iron-rich brine plumes under the Antarctic ice sheets. Such subglacial environments could have potentially provided a habitable “refuge” for early life to survive during the Neoproterozoic glaciation.

Open-Endedness in Genelife.

We explore the open-ended nature of evolution in Genelife, an evolutionary extension of Conway's Game of Life cellular automaton in which "live" cell states are endowed at birth with a genome that affects their local dynamics and can be inherited. Both genetic sequences and locally connected spatial patterns are analyzed for novelty, keeping track of all new structures, and innovation is quantified using activity statistics. The impacts of both spatial symmetry breaking with nontotalistic rules and superimposed density regulation of the live state proliferation on the open-ended nature of the evolution are explored. Conditions are found where both genetic and spatial patterns exhibit open-ended innovation. This innovation appears to fall short of functional biological innovation, however, and potential reasons for this are discussed.

Transforming yeast into a facultative photoheterotroph via expression of vacuolar rhodopsin

Phototrophic metabolism, the capture of light for energy, was a pivotal biological innovation that greatly increased the total energy available to the biosphere. Chlorophyll-based photosynthesis is the most familiar phototrophic metabolism, but retinal-based microbial rhodopsins transduce nearly as much light energy as chlorophyll does,1 via a simpler mechanism, and are found in far more taxonomic groups. Although this system has apparently spread widely via horizontal gene transfer,2,3,4 little is known about how rhodopsin genes (with phylogenetic origins within prokaryotes5,6) are horizontally acquired by eukaryotic cells with complex internal membrane architectures or the conditions under which they provide a fitness advantage. To address this knowledge gap, we sought to determine whether Saccharomyces cerevisiae, a heterotrophic yeast with no known evolutionary history of phototrophy, can function as a facultative photoheterotroph after acquiring a single rhodopsin gene. We inserted a rhodopsin gene from Ustilago maydis,7 which encodes a proton pump localized to the vacuole, an organelle normally acidified via a V-type rotary ATPase, allowing the rhodopsin to supplement heterotrophic metabolism. Probes of the physiology of modified cells show that they can deacidify the cytoplasm using light energy, demonstrating the ability of rhodopsins to ameliorate the effects of starvation and quiescence. Further, we show that yeast-bearing rhodopsins gain a selective advantage when illuminated, proliferating more rapidly than their non-phototrophic ancestor or rhodopsin-bearing yeast cultured in the dark. These results underscore the ease with which rhodopsins may be horizontally transferred even in eukaryotes, providing novel biological function without first requiring evolutionary optimization.

Standard-of-Care Treatment for HER2+ Metastatic Breast Cancer and Emerging Therapeutic Options.

Prior to the advent of the HER2-targeted monoclonal antibody trastuzumab, HER2+ breast cancer (BC) was considered an aggressive disease with a poor prognosis. Over the past 25 years, innovations in molecular biology, pathology, and early therapeutics have transformed the treatment landscape. With the advent of multiple HER2-directed therapies, there have been immense improvements in oncological outcomes in both adjuvant and metastatic settings. Currently, 8 HER2-targeted therapies are approved by the Food and Drug Administration (FDA) for the treatment of early-stage and/or advanced/metastatic disease. Nonetheless, approximately 25% of patients develop recurrent disease or metastasis after HER2-targeted therapy and most patients with HER2+ metastatic breast cancer (MBC) die from their disease. Given the many mechanisms of resistance to HER2-directed therapy, there is a pressing need to further personalize care for patients with HER2+ MBC, by the identification of reliable predictive biomarkers, and the development of novel therapies and combination regimens to overcome therapeutic resistance. Of particular interest are established and novel antibody-drug conjugates, as well as other novel therapeutics and multifaceted approaches to harness the immune system (checkpoint inhibitors, bispecific antibodies, and vaccine therapy). Herein, we discuss standard-of-care treatment of HER2+ MBC, including the management of breast cancer brain metastases (BCBM). Furthermore, we highlight novel treatment approaches for HER2+ MBC, including endeavors to personalize therapy, and discuss ongoing controversies and challenges.

Applying new approach methodologies to assess next-generation tobacco and nicotine products.

In vitro toxicology research has accelerated with the use of in silico, computational approaches and human in vitro tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput in vitro cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches. Routine toxicological methods are largely unchanged since development over 50 years ago, using high-doses and often employing in vivo testing. Several disadvantages are encountered conducting or extrapolating data from animal studies due to differences in metabolism or exposure. The last decade saw considerable advancement in the development of in vitro tools and capabilities, and the challenges of the next decade will be integrating these platforms into applied product testing and acceptance by regulatory bodies. Governmental and validation agencies have launched and applied frameworks and "roadmaps" to support agile validation and acceptance of NAMs. Next-generation tobacco and nicotine products (NGPs) have the potential to offer reduced risks to smokers compared to cigarettes. These include heated tobacco products (HTPs) that heat but do not burn tobacco; vapor products also termed electronic nicotine delivery systems (ENDS), that heat an e-liquid to produce an inhalable aerosol; oral smokeless tobacco products (e.g., Swedish-style snus) and tobacco-free oral nicotine pouches. With the increased availability of NGPs and the requirement of scientific studies to support regulatory approval, NAMs approaches can supplement the assessment of NGPs. This review explores how NAMs can be applied to assess NGPs, highlighting key considerations, including the use of appropriate in vitro model systems, deploying screening approaches for hazard identification, and the importance of test article characterization. The importance and opportunity for fit-for-purpose testing and method standardization are discussed, highlighting the value of industry and cross-industry collaborations. Supporting the development of methods that are accepted by regulatory bodies could lead to the implementation of NAMs for tobacco and nicotine NGP testing.

Bio-inspired Frugal Engineering Strategies for Resilient Supply Chains

This paper is aimed at the application of frugal engineering methods for enhancing the resilience of manufacturing supply chains. The frugal engineering methods are presented by discovering the cross-section of biological designs and equitable social innovations. Multiple global trends such as urbanization, climate changes, pandemics, growing global population, and others pose serious challenges to resiliency in manufacturing enterprises including supply chains. These challenges call for the development of novel and ‘out-of-box’ approaches to solutions. Biology achieves the co-existence of millions of species across varying habitats and disturbances for survival while maximizing the available resources through the utilization of frugality or frugal engineering principles. Strategies applied in biology deliver a collective balance for multifunctionality, resilience, and frugality while balancing the trade-offs between efficacy, effectiveness, and efficiency. Frugality in this context is defined as the philosophy to minimize the use of available resources while maximizing the productive outputs. This concept of frugality has been increasingly used over the past few years, especially in business and sociological contexts to deliver social innovations. The paper discusses examples from biology and social innovations and critical analysis of the example case studies to propose a framework for frugal engineering-driven strategies for supply chain resilience in manufacturing. A hybrid model is proposed for a regionally resilient distributed network of micro supply chains that complement the giga-global supply chains.

The reform and practice of biology innovation and entrepreneurship education aiming at improving both ability and quality-- Southwest Forestry University explores the “industry-university-research” collaborative education model

"Industry-university-research" collaborative education mode is a kind of personnel training mode that closely combines industry, academia and research. This study aims to explore the reform and practice of biological innovation and entrepreneurship education with the goal of improving both ability and quality, and focuses on the application and effect of "industry-university-research" collaborative education mode. Through in-depth analysis of the current situation and problems of biology education, we aim to put forward targeted reform measures and methods to provide useful reference for the development of biology education.

CellWalker: a user-friendly and modular computational pipeline for morphological analysis of microscopy images.

The implementation of computational tools for analysis of microscopy images has been one of the most important technological innovations in biology, providing researchers unmatched capabilities to comprehend cell shape and connectivity. While numerous tools exist for image annotation and segmentation, there is a noticeable gap when it comes to morphometric analysis of microscopy images. Most existing tools often measure features solely on 2D serial images, which can be difficult to extrapolate to 3D. For this reason, we introduce CellWalker, a computational toolbox that runs inside Blender, an open-source computer graphics software. This add-on improves the morphological analysis by seamlessly integrating analysis tools into the Blender workflow, providing visual feedback through a powerful 3D visualization, and leveraging the resources of Blender's community. CellWalker provides several morphometric analysis tools that can be used to calculate distances, volume, surface areas and to determine cross-sectional properties. It also includes tools to build skeletons, calculate distributions of subcellular organelles. In addition, this python-based tool contains 'visible-source' IPython notebooks accessories for segmentation of 2D/3D microscopy images using deep learning and visualization of the segmented images that are required as input to CellWalker. Overall, CellWalker provides practical tools for segmentation and morphological analysis of microscopy images in the form of an open-source and modular pipeline which allows a complete access to fine-tuning of algorithms through visible-source code while still retaining a result-oriented interface. CellWalker source code is available on GitHub (https://github.com/utraf-pasteur-institute/Cellwalker-blender and https://github.com/utraf-pasteur-institute/Cellwalker-notebooks) under a GPL-3 license.

Revolutionizing Biological Science: The Synergy of Genomics in Health, Bioinformatics, Agriculture, and Artificial Intelligence.

With climate emergency, COVID-19, and the rise of planetary health scholarship, the binary of human and ecosystem health has been deeply challenged. The interdependence of human and nonhuman animal health is increasingly acknowledged and paving the way for new frontiers in integrative biology. The convergence of genomics in health, bioinformatics, agriculture, and artificial intelligence (AI) has ushered in a new era of possibilities and applications. However, the sheer volume of genomic/multiomics big data generated also presents formidable sociotechnical challenges in extracting meaningful biological, planetary health and ecological insights. Over the past few years, AI-guided bioinformatics has emerged as a powerful tool for managing, analyzing, and interpreting complex biological datasets. The advances in AI, particularly in machine learning and deep learning, have been transforming the fields of genomics, planetary health, and agriculture. This article aims to unpack and explore the formidable range of possibilities and challenges that result from such transdisciplinary integration, and emphasizes its radically transformative potential for human and ecosystem health. The integration of these disciplines is also driving significant advancements in precision medicine and personalized health care. This presents an unprecedented opportunity to deepen our understanding of complex biological systems and advance the well-being of all life in planetary ecosystems. Notwithstanding in mind its sociotechnical, ethical, and critical policy challenges, the integration of genomics, multiomics, planetary health, and agriculture with AI-guided bioinformatics opens up vast opportunities for transnational collaborative efforts, data sharing, analysis, valorization, and interdisciplinary innovations in life sciences and integrative biology.

A Tale of Enduring Myths: Buffon’s Theory of Animal Degeneration and the Regeneration of Domesticated Animals in Mid-19th Century Brazil

The long 19th century was a period of many developments and technical innovations in agriculture and animal biology, during which actors sought to incorporate new practices in light of new information. By the middle of the century, however, while heredity steadily became the dominant concept in animal husbandry, some policies related to livestock improvement in Brazil seemed to have been tailored following a climate-deterministic concept established in the mid-18th century by the French naturalist Georges-Louis Leclerc, the Comte de Buffon. His theory of animal degeneration posited, among other things, the necessity of recurrent crossbreeding to preserve animal species living in nonnative environments from climate-induced degeneration. Although largely discredited by the early 19th century, the teachings of the French naturalist seem to have found supporters in a Brazilian program to modernize national agriculture through the application of the natural sciences. Herein I examine the revival of Buffon’s theories in that government-sponsored program to improve animal husbandry and breeding techniques, including actual applications of this theory in the real world. Ultimately, I argue that Buffon’s theory of degeneration was used to tailor public policies and funding for the improvement of domesticated animals in Brazil between 1856 and 1860.

Robust Phylogenetic Regression.

Modern comparative biology owes much to phylogenetic regression. At its conception, this technique sparked a revolution that armed biologists with phylogenetic comparative methods (PCMs) for disentangling evolutionary correlations from those arising from hierarchical phylogenetic relationships. Over the past few decades, the phylogenetic regression framework has become a paradigm of modern comparative biology that has been widely embraced as a remedy for shared ancestry. However, recent evidence has shown doubt over the efficacy of phylogenetic regression, and PCMs more generally, with the suggestion that many of these methods fail to provide an adequate defense against unreplicated evolution-the primary justification for using them in the first place. Importantly, some of the most compelling examples of biological innovation in nature result from abrupt lineage-specific evolutionary shifts, which current regression models are largely ill equipped to deal with. Here we explore a solution to this problem by applying robust linear regression to comparative trait data. We formally introduce robust phylogenetic regression to the PCM toolkit with linear estimators that are less sensitive to model violations than the standard least-squares estimator, while still retaining high power to detect true trait associations. Our analyses also highlight an ingenuity of the original algorithm for phylogenetic regression based on independent contrasts, whereby robust estimators are particularly effective. Collectively, we find that robust estimators hold promise for improving tests of trait associations and offer a path forward in scenarios where classical approaches may fail. Our study joins recent arguments for increased vigilance against unreplicated evolution and a better understanding of evolutionary model performance in challenging-yet biologically important-settings.

Strongly peraluminous granites provide independent evidence for an increase in biomass burial across the Precambrian–Phanerozoic boundary

Abstract Strongly peraluminous granites (SPGs) are generated by the partial melting of sedimentary rocks and can thus provide a novel archive to reveal secular trends in Earth’s environmental history that integrate siliciclastic sedimentary lithologies. The nitrogen (N) content of Archean, Proterozoic, and Phanerozoic SPGs reveals a systematic increase across the Precambrian–Phanerozoic boundary. This rise is supported by a coeval increase in the phosphorus (P) contents of SPGs. Collectively, these data are most parsimoniously explained by an absolute increase in biomass burial in the late Proterozoic or early Phanerozoic by a factor of ~5 and as much as 8. The Precambrian–Phanerozoic transition was a time of progressive oxygenation of surface environments paired with major biological innovations, including the rise of eukaryotic algae to ecological dominance. Because oxygenation suppresses biomass preservation in sediments, the increase in net biomass burial preserved in SPGs reveals an expansion of the biosphere and an increase in primary production across this interval.

PENINGKATAN KEAKTIFAN DAN HASIL BELAJAR MELALUI MODEL PEMBELAJARAN PROBLEM BASED LEARNING MATERI INOVASI TEKNOLOGI BIOLOGI KELAS X A SMAN 6 MADIUN TAHUN PELAJARAN 2022/2023

The purpose of this study was to increase the activity and learning outcomes of students in biology learning material for biological technology innovation in class XA SMAN 6 Madiun by applying the Problem Based Learning learning model.This research is a class action research (CAR) with the Kemmis & Taggart model which was carried out in two cycles. The data collected was in the form of data on students' active learning and cognitive learning outcomes, namely the pre-test and post-test scores of cycles I and II. Data on students' learning activeness was taken by observation and analyzed descriptively by describing the percentage of each aspect in learning activeness. Cognitive learning outcomes data were taken by pre-test and post-test cycle I-cycle II and tabulated in the form of class averages. The increase in students' cognitive learning outcomes can be seen from the difference between the mean value of the second cycle post-test and the first cycle post-test average value. The results showed that the application of the Problem Based Learning (PBL) learning model in biology subject material Biological Technology Innovation could increase the activity and cognitive learning outcomes of class X A students of SMAN 6 Madiun. Increasing the activeness of learning students can be seen from each aspect of activeness.

FRI008 Impact Of Sleep Fragmentation And Estradiol Suppression On Leptin, Ghrelin, Satiety And Hunger In Women: An Experimental Menopause Model To Understand Menopause-related Body Fat Gain

Abstract Disclosure: S.A. Rahman: Consulting Fee; Self; Sultan & Knight Limited, Bambu Vault LLC, Lucidity Lighting Inc. Grant Recipient; Self; Seoul Semiconductor Co. Ltd, Biological Innovation and Optimization Systems, LLC, Merck & Co, Inc, Pfizer Inc, Vanda Pharmaceuticals Inc, Lighting Science Group. Speaker; Self; Starry Skies Lake Superior, University of Minnesota Medical School, PennWell Corp, and Seoul Semiconductor Co. Ltd. Stock Owner; Self; Melcort Inc. L.K. Grant: None. A. Cohn: None. M.D. Nathan: None. J. Harder: Consulting Fee; Self; Atman Health; O’Rourke & Hawk, LLP. Grant Recipient; Self; Brigham and Women’s Hospital; President and Fellows of Harvard College. Owner/Co-Owner; Self; Jessica Harder, MD. Stock Owner; Self; Atman Health. Other; Self; Centerfield Media Holding Company. I. Gonsalvez: None. F.A. Scheer: Consulting Fee; Self; University of Alabama at Birmingham. Other; Self; Board of Directors for the Sleep Research Society. E.B. Klerman: Consulting Fee; Self; Circadian Therapeutics, The National Sleep Foundation, Sanofi-Genzynel. Other; Self; Travel support from the Sleep Research Society. S. Crawford: None. T. Luo: None. E. Menezes: None. A. Roy: None. A. Joseph: None. A. Wiley: None. U.B. Kaiser: None. H. Joffe: Consulting Fee; Self; Bayer, Hello Therapeutics. Grant Recipient; Self; National Institutes of Health, Merck, Pfizer. Body fat increases during the menopause transition. In addition to menopause-related estradiol (E2) decline, sleep fragmentation (wake episodes interrupting sleep) due to hot flashes, without a reduction in total sleep time, is common. We examined whether E2 decline and sleep fragmentation decrease the satiety hormone, leptin, increase the orexigenic hormone, ghrelin, and their behavioral correlates satiety and hunger, which would promote positive energy balance and body fat gain. We studied 38 healthy premenopausal female volunteers (mean age [±SD] 29.7±6.7 years) in a 5-night inpatient study under eucaloric conditions, once in the mid-to-late follicular phase (high-E2) and again after gonadotropin-releasing hormone agonist-induced E2-suppression (hypo-E2) in a subset (n=27). Each inpatient study involved 2 nights of unfragmented sleep followed by 3 nights of experimentally induced sleep fragmentation to achieve ∼1hr of wake after sleep-onset without reducing total sleep time. Serum for leptin and acetylated ghrelin assays and self-reported satiety and hunger via visual analog scales were collected fasting ∼1hr after waking each morning. Values were normalized relative to each individual’s baseline (high-E2, unfragmented sleep) and then compared between conditions using generalized linear mixed models. Mean (±SD) levels of leptin and ghrelin at baseline were 38.5±21.2 ng/mL and 640.9±362.0 pg/mL, respectively. Compared to the high-E2 state, omnibus analysis of E2 suppression during both unfragmented and fragmented sleep showed significant reduction from the high-E2 to hypo-E2 state in satiety-promoting leptin levels (least squares mean % of baseline [±SE]: 101.0±1.1% vs. 90.0±3.0%, p=0.001), but unchanged self-rated satiety (109.3±7.8% vs. 102.6±15.6%, p=0.58). E2 suppression also did not change hunger-promoting ghrelin levels (101.0±3.1% vs. 97.0±1.4%, p=0.13) or self-rated hunger (103.3±6.6% vs. 133.2±30.5%, p=0.28). Omnibus analysis of sleep fragmentation during both high-E2 and hypo-E2 states showed that, relative to unfragmented sleep, leptin levels were unchanged (94.0±1.5% vs. 96.7±2.5%, p=0.22), but self-rated satiety was significantly lower (113.1±11.0% vs. 99.2±11.9%, p=0.048) after sleep fragmentation. There was a trend towards the lowest satiety in the hypo-E2 sleep fragmented state (interaction p=0.052). Sleep fragmentation did not change ghrelin levels (100.7±1.8% vs. 97.3±2.7%, p=0.13) or self-rated hunger (103.0±6.2% vs. 133.6±30.0%, p=0.25). These results demonstrate significant adverse changes in leptin and satiety in women induced, respectively, by E2 suppression and sleep fragmentation, independent of aging. Findings support likely independent contributions of E2 decline and sleep fragmentation during the menopause transition toward positive energy balance and body fat gain. Funding: NIH R01AG053838 (PI: H Joffe). Presentation: Friday, June 16, 2023

FRI411 Pharmacologically Induced Hypoestrogenism And Experimentally Induced Menopause-Pattern Sleep Fragmentation Independently Influence Circulating Lipids, Heart Rate, And Blood Pressure In Women

Abstract Disclosure: L.K. Grant: Grant Recipient; Self; Brigham and Women’s Hospital, Women’s Health Access Matters. A. Cohn: None. S. Crawford: None. J. Harder: Consulting Fee; Self; Altman Health, O’Rouke & Hawk, LLP. Grant Recipient; Self; Brigham and Women’s Hospital, President and Fellows of Harvard College. Owner/Co-Owner; Self; Jessica Harder, MD. Stock Owner; Self; Altman Health. Other; Self; Centerfield Media Holding Company. M.D. Nathan: None. I. Gonsalvez: None. T. Luo: None. E. Menezes: None. A. Roy: None. A. Wiley: None. F.A. Scheer: Consulting Fee; Self; University of Alabama. Other; Self; Board of Directors for the Sleep Research Society. E. Klerman: Consulting Fee; Self; American Academy of Sleep Medicine Foundation, Sleep Research Society Foundation, Circadian Therapeutics, National Sleep Foundation, Yale University Press. U.B. Kaiser: None. S. Mora: Consulting Fee; Self; Pfizer, Inc. J. Taylor: None. H. Joffe: Consulting Fee; Self; Bayer, Inc., Hello Therapeutics. Grant Recipient; Self; Merck, Pfizer, Inc., NIH. S.A. Rahman: Consulting Fee; Self; Sultan & Knight Limited, Bambu Vault LLC, Lucidity Lighting Inc. Grant Recipient; Self; Seoul Semiconductor Co. Ltd, Biological Innovation and Optimization Systems, LLC, Pfizer, Inc., Merck & Co., Lighting Science Group. Speaker; Self; Starry Skies Lake Superior, University of Minnesota Medical School, PennWell Corp, Seoul Semiconductor Co. Ltd. Stock Owner; Self; Melcort Inc. Introduction: The risk of cardiovascular disease (CVD) in women increases at menopause. Although declining levels of estradiol (E2) have been implicated in the increase in CVD risk for midlife women, it remains difficult to isolate these effects from the parallel changes in chronological age, and other potential contributing, mediating and modifying factors such as menopause-pattern sleep fragmentation (increased awakenings but no change in overall sleep duration). Here, we investigated whether hypo-estrogenism (hypo-E2) and sleep fragmentation increase CVD risk factors [lipids, blood pressure (BP)] in an experimental menopause model implemented in premenopausal women. Method: Two 5-night inpatient studies performed in the mid-to-late follicular phase (E2 = 48.7±29.5 pg/mL) and repeated following leuprolide-induced hypo-E2 (E2 = 7.5±5.9 pg/mL) were completed in 27 premenopausal women (mean age = 28.4±5.6 years). Each admission involved 2 nights of unfragmented sleep [8-h time-in-bed (TIB)] followed by 3 nights of sleep fragmentation, induced by auditory stimuli distributed across the night, producing 1-hr of cumulative wakefulness while enabling equal sleep opportunity (9-h TIB). BP and heart rate (HR) measurements were collected within 1 hour of wake in a semi-supine position each morning; fasting serum lipids were collected during unfragmented sleep and again after 3 nights of sleep fragmentation, during both inpatient stays. The effect of sleep fragmentation, E2 state and their interaction were assessed using generalized linear models to account for repeated measures. Results: Relative to the estrogenized state, the hypo-E2 state had a significant increase in total cholesterol (156±5 vs. 167±6 mg/dL, p<.001), triglycerides (72±5 vs 79±7 mg/dL, p<.001), HDL-C (58±3 vs. 62±3 mg/dL, p<.01), LDL-C (81±4 vs. 86±5 mg/dL, p<.05) and mean arterial pressure (MAP; 79±1 vs. 81±1 mmHg, p<.05) and a trend toward increased diastolic BP (63±1 vs. 65±1 mmHg, p=.07), with a significant compensatory decrease in HR (67±2 vs. 65±2 bpm, p<.001). Compared to the unfragmented sleep condition, sleep fragmentation resulted in a significant increase in HR (64±2 vs. 68±2 bpm, p<.001) and a trend toward increased systolic BP (109±1 vs. 110±1 mmHg, p=.08). There was no effect of sleep fragmentation on lipid levels, diastolic BP, or MAP, and no interaction between sleep fragmentation and E2 for any of the variables. Conclusion: These experimental findings show that pharmacologically induced hypo-E2, but not sleep fragmentation, increase circulating lipids levels in pre-menopausal women. Additionally, pharmacological E2-suppression increased BP and decreased HR, whereas sleep fragmentation increased both BP and HR. Together, these findings suggest that both E2 decline, and sleep fragmentation may uniquely contribute to the increase in CVD risk during the menopause transition. Presentation: Friday, June 16, 2023

Divergence time estimates for the hypoxia-inducible factor-1 alpha (HIF1α) reveal an ancient emergence of animals in low-oxygen environments.

Unveiling the tempo and mode of animal evolution is necessary to understand the links between environmental changes and biological innovation. Although the earliest unambiguous metazoan fossils date to the late Ediacaran period, molecular clock estimates agree that the last common ancestor (LCA) of all extant animals emerged ~850 Ma, in the Tonian period, before the oldest evidence for widespread ocean oxygenation at ~635-560 Ma in the Ediacaran period. Metazoans are aerobic organisms, that is, they are dependent on oxygen to survive. In low-oxygen conditions, most animals have an evolutionarily conserved pathway for maintaining oxygen homeostasis that triggers physiological changes in gene expression via the hypoxia-inducible factor (HIFa). However, here we confirm the absence of the characteristic HIFa protein domain responsible for the oxygen sensing of HIFa in sponges and ctenophores, indicating the LCA of metazoans lacked the functional protein domain as well, and so could have maintained their transcription levels unaltered under the very low-oxygen concentrations of their environments. Using Bayesian relaxed molecular clock dating, we inferred that the ancestral gene lineage responsible for HIFa arose in the Mesoproterozoic Era, ~1273 Ma (Credibility Interval 957-1621 Ma), consistent with the idea that important genetic machinery associated with animals evolved much earlier than the LCA of animals. Our data suggest at least two duplication events in the evolutionary history of HIFa, which generated three vertebrate paralogs, products of the two successive whole-genome duplications that occurred in the vertebrate LCA. Overall, our results support the hypothesis of a pre-Tonian emergence of metazoans under low-oxygen conditions, and an increase in oxygen response elements during animal evolution.