bioRxiv最新文献

{"title":"Elevational constraints on flight efficiency shape global gradients in avian wing morphology","authors":"Jingyi Yang, Chenyue Yang, Hung-wei Lin, Alexander C. Lees, Joseph A. Tobias","doi":"10.1101/2024.07.12.603304","DOIUrl":"https://doi.org/10.1101/2024.07.12.603304","url":null,"abstract":"Wings with elongated shape or larger surface area are associated with increased flight efficiency and dispersal ability in a wide range of animals from insects to birds 1–4. Inter- and intraspecific variation in these attributes of wing shape is determined by a range of factors – including foraging ecology, migration and climatic seasonality 5–8 – all of which may drive latitudinal gradients in wing morphology 9,10. A separate hypothesis predicts that wing shape should also follow an elevational gradient because air density and oxygen supply decline with altitude 11, altering the aerodynamics of flight, and driving the evolution of more efficient wings in high-elevation species to compensate for reduced lift 12,13. However, previous analyses have found only mixed support for the ‘thin-air’ hypothesis 14–18, and we currently lack a global synthesis of elevational gradients in wing design for any taxonomic group. In this study, we use phylogenetic comparative models to explore elevational effects on wing morphology in 9986 bird species, while accounting for multiple climatic and ecological attributes, including latitude, temperature seasonality, body mass, aerial lifestyle and migration. We found that relative wing elongation (hand-wing index) and wing area increase with elevation, particularly in the upper montane zone (>4 km above sea level). These results confirm a pervasive elevational gradient in avian wing morphology, highlighting the role of aerodynamic constraints as key mechanisms shaping global patterns of trait evolution in flying animals.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"4 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse Genomic Embedding Benchmark for functional evaluation across the tree of life","authors":"Jacob West-Roberts, Joshua Kravitz, Nishant Jha, Andre L. Cornman, Yunha Hwang","doi":"10.1101/2024.07.10.602933","DOIUrl":"https://doi.org/10.1101/2024.07.10.602933","url":null,"abstract":"Biological foundation models hold significant promise for deciphering complex biological functions. However, evaluating their performance on functional tasks remains challenging due to the lack of standardized benchmarks encompassing diverse sequences and functions. Existing functional annotations are often scarce, biased, and susceptible to train-test leakage, hindering robust evaluation. Furthermore, biological functions manifest at multiple scales, from individual residues to large genomic segments. To address these limitations, we introduce the Diverse Genomic Embedding Benchmark (DGEB), inspired by natural language embedding benchmarks. DGEB comprises six embedding tasks across 18 expert curated datasets, spanning sequences from all domains of life and encompassing both nucleic acid and amino acid modalities. Notably, four datasets enable direct comparison between models trained on different modalities. Benchmarking protein and genomic language models (pLMs and gLMs) on DGEB reveals performance saturation with model scaling on numerous tasks, especially on those with underrepresented sequences (e.g. Archaea). This highlights the limitations of existing modeling objectives and training data distributions for capturing diverse biological functions. DGEB is available as an open-source package with a public leaderboard at https://github.com/TattaBio/DGEB.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness","authors":"Nasrin Mortazavi, Puneet Talwar, Ekaterina Koshmanova, Roya Sharifpour, E. Beckers, Alexandre Berger, Islay Campbell, Ilenia Paparella, F. Balda, Ismael Dardour Hamzaoui, C. Berthomier, Christine Bastin, Christophe Phillips, Pierre Maquet, F. Collette, Mikhail Zubkov, Laurent Lamalle, Gilles Vandewalle","doi":"10.1101/2024.07.12.603275","DOIUrl":"https://doi.org/10.1101/2024.07.12.603275","url":null,"abstract":"Objective Animal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to sleep variability in humans is not yet established. Here, we investigated if the in vivo activity of the LC is related to the variability in the quality of Rapid Eye Movement (REM) sleep. Methods We assessed the LC activity of 34 healthy younger (∼22y) and 18 older (∼61y) individuals engaged in bottom-up and top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). We further recorded their sleep electroencephalogram (EEG) to evaluate associations between LC fMRI measures and REM sleep EEG metrics. Results Theta oscillation energy during REM sleep was positively associated with LC response in the top-down task. In contrast, REM sleep theta energy was negatively associated with LC activity in older individuals during the bottom-up task. Importantly, sigma oscillations power immediately preceding a REM sleep episode was positively associated with LC activity in the top-down task. Interpretation LC activity during wakefulness was related to REM sleep intensity and to a transient EEG change preceding REM sleep, a feature causally related to LC activity in animal studies. The associations depend on the cognitive task, suggesting that a balanced level of LC tonic activity during wakefulness is required for optimal expression of REM sleep. The findings may have implications for the high prevalence of sleep complaints reported in aging and for disorders such as insomnia, Alzheimer’s, and Parkinson’s disease, for which the LC may play pivotal roles through sleep.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"29 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context-dependent roles for autophagy in myeloid cells in tumor progression","authors":"Jayoung Choi, Gayoung Park, Steve Seung-Young Lee, Erin M Dominici, Lev Becker, Kay F. Macleod, Stephen J. Kron, Seungmin Hwang","doi":"10.1101/2024.07.12.603292","DOIUrl":"https://doi.org/10.1101/2024.07.12.603292","url":null,"abstract":"Autophagy is known to suppress tumor initiation by removing genotoxic stresses in normal cells. Conversely, autophagy is also known to support tumor progression by alleviating metabolic stresses in neoplastic cells. Centered on this pro-tumor role of autophagy, there have been many clinical trials to treat cancers through systemic blocking of autophagy. Such systemic inhibition affects both tumor cells and non-tumor cells, and the consequence of blocked autophagy in non-tumor cells in the context of tumor microenvironment is relatively understudied. Here, we examined the effect of autophagy-deficient myeloid cells on the progression of autophagy-competent tumors. We found that blocking autophagy only in myeloid cells modulated tumor progression markedly but such effects were context dependent. In a tumor implantation model, the growth of implanted tumor cells was substantially reduced in mice with autophagy-deficient myeloid cells; T cells infiltrated deeper into the tumors and were responsible for the reduced growth of the implanted tumor cells. In an oncogene-driven tumor induction model, however, tumors grew faster and metastasized more in mice with autophagy- deficient myeloid cells. These data demonstrate that the autophagy status of myeloid cells plays a critical role in tumor progression, promoting or suppressing tumor growth depending on the context of tumor-myeloid cell interactions. This study indicates that systemic use of autophagy inhibitors in cancer therapy may have differential effects on rates of tumor progression in patients due to effects on myeloid cells and that this warrants more targeted use of selective autophagy inhibitors in a cancer therapy in a clinical setting.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"9 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapting Lateral Stepping Control to Walk on Winding Paths","authors":"Anna C. Render, J. Cusumano, J. Dingwell","doi":"10.1101/2024.07.11.603068","DOIUrl":"https://doi.org/10.1101/2024.07.11.603068","url":null,"abstract":"Most often, gait biomechanics is studied during straight-ahead walking. However, real-life walking imposes many turns and/or other maneuvers people must navigate. Such maneuvers challenge people’s lateral balance and can frequently induce falls. Determining how people regulate their stepping movements to maintain balance during complex walking tasks is therefore essential. Here, 24 adults (12F/12M; Age 25.8±3.5yrs) walked on wide or narrow virtual paths that were either straight, slowly-winding, or quickly-winding. From each trial, we computed time series of step widths and lateral positions relative to the path. We applied our Goal Equivalent Manifold framework to quantify how participants adjusted their lateral stepping and step-to-step corrections of step width and lateral position as they walked on these different paths. On the narrower paths, participants walked with narrower steps and less lateral position variability. They did so by correcting step-to-step deviations in lateral position more, while correcting step-to-step deviations in step width less. On the winding paths, participants took both narrower and more variable steps. Interestingly, on slowly-winding paths, participants corrected step-to-step deviations in step width more by correcting step-to-step deviations in lateral position less: i.e., they prioritized maintaining step width over position, likely to maintain lateral balance. Conversely, on quickly-winding paths, participants strongly corrected step-to-step deviations in both step width and lateral position: i.e., they prioritized maintaining both approximately equally, consistent with trying to maximize their maneuverability. These findings have important implications for persons with gait impairments who may have elevated fall risk.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"60 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited protection against early-life cytomegalovirus infection results from deficiency of cytotoxic CD8 T cells","authors":"Luís Fonseca Brito, E. Ostermann, Anna Perez, Silvia Tödter, Sanamjeet Virdi, D. Indenbirken, L. Glau, A. Gieras, Renke Brixel, Ramon Arens, Adam Grundhoff, P. Arck, Anke Diemert, Eva Tolosa, Wolfram Brune, F. Stahl","doi":"10.1101/2024.07.10.602923","DOIUrl":"https://doi.org/10.1101/2024.07.10.602923","url":null,"abstract":"Differential antiviral T cell immunity in early life impacts the clinical outcome of Cytomegalovirus (CMV) infection, but the underlying mechanisms are not well understood. Here, we found delayed enrichment of early-life murine CMV-specific CD8 T cells due to a general deficiency of αβ T cells. Adoptive transfer of naïve adult T cells into neonates did not protect due to a blockade of CD8 but not of CD4 effector T cell differentiation. Early-life deficiency of critical signal 3 cytokines during T cell priming resulted in the appearance of non-cytotoxic CD8 effector T cells whereas the effector phase of adult-primed T cells was not disrupted in neonates. Accordingly, we found an overall low number of antiviral human CD8 T cells in newborns with congenital CMV. Together, this study suggests defective CD8 T cell immunity as an important factor explaining the higher risk for CMV disease in the early-life phase.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparisons of Tree Damage Indicators in Five NASA ABoVE Forest Sites Near Fairbanks, Alaska","authors":"D. Huebner, Christopher S. Potter","doi":"10.1101/2024.07.10.602861","DOIUrl":"https://doi.org/10.1101/2024.07.10.602861","url":null,"abstract":"As global warming affects sensitive northern regions, forests near Fairbanks, Alaska may be undergoing attack from pests and pathogens that could impact their ability to store carbon. Visual tree surveys are quick and useful for assessing forest health in remote sensing studies using GT (ground-truthing). Initial spectral analysis of leaf pigments, canopy water content, and non-photosynthetic carbon of one site near Fairbanks, Alaska imaged with AVIRIS-NG by NASA for the Arctic and Boreal Vulnerability Experiment (ABoVE) showed high fire fuel loads in 2017 that burned in 2019. In 2021-2022 we visually assayed damage of 359 deciduous and 309 coniferous trees at five ABoVE sites of different moisture regimes and burn severities. Using indices of 0 - 5 (0 = healthy, 5 = severe damage) we calculated average damage per tree from: 1) leaf damage (holes or defoliation); 2) stem damage (changes in stem color, texture, growth, heartwood, sap ooze, or stem loss); 3) non-photosynthetic tissue, aka “browning”; and 4) wilting. We also characterized crown color tree-1. Least squares models found low overall average tree damage, but damage types were varied and complex. Deciduous trees suffered greater herbivore damage than conifers. A third of trees showed broadleaf insect damage, a tenth of trees across species showed stem damage associated with pathogens. Aspen and conifers showed heartwood rot, but we found no visual signs of spruce beetle at our sites. Structural equation models found greater stem damage and wilting in warmer soils and post-burned sites supporting seedlings. Browning was associated with understory branches of conifers in late-successional sites with colder, shallower soils. Our study suggests that deciduous trees and seedlings near Fairbanks, Alaska are experiencing herbivory and midsummer wilting, and conifer understory browning is common.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-male sperm precedence in polyandrous Spodoptera frugiperda allows sterile males induce population suppression","authors":"Hao Sun, Ling-Ao Bu, Xin-Yue Zhang, Zhi-Ruo Zhang, Ling-Yi Zhu, Shao-Cong Su, Di Guo, Gao Hu, Cong-Fen Gao, S. R. Palli, J. Champer, Shun-Fan Wu","doi":"10.1101/2024.07.10.602994","DOIUrl":"https://doi.org/10.1101/2024.07.10.602994","url":null,"abstract":"Males respond to intense sperm competition by adapting reproductive strategies to promote fertilization success, which is critical for population reproduction. Thus, investigating the patterns and mechanisms of sperm competition is crucial for the development and application of pest population management techniques. In this study, we analyzed the sperm precedence pattern of a major pest, the fall armyworm, and used this pattern to manage the pest population. First, we found that females had a post-mating response and did not gain direct benefit through multiple mating. Next, in a double mating experiment, we used a molecular marker created by CRISPR/Cas9 to determine that most females use only the sperm of the first male to produce offspring. To further explore the role of fertilizing sperm in sperm competition, we constructed a sterile male line with eupyrene sperm defect by knocking out the B2t gene. Interestingly, two round mating assays showed that first mating with B2t-null males inhibited sperm fertilization from a second wild-type male. In other words, prior mating with B2t-null males significantly reduced the fertility and fecundity of females. Based on this finding, we continued to explore whether sperm-deficient sterile males could be used in the management of FAW populations. Cage experiments and mathematical modeling analyses showed that the release of excess B2t-null males induced population suppression. Our study expands our knowledge of sperm competition patterns in lepidopteran. In addition, our study provides a paradigm to develop and apply genetic control methods based on sperm competition outcome in polyandrous pests. Significance Sperm competition is essential for maintaining population reproduction. Understanding patterns and mechanisms of sperm competition facilitates the development of appropriate pest genetic control methods. Here, we describe that a globally major pest, the fall armyworm displays the first-male sperm precedence pattern. Interestingly, first mating with B2t-null males, which produces non-functional eupyrene sperm, significantly reduces the fertility and fecundity of females. That means that the ejaculate of the first male, even if its eupyrene sperm are defective, can inhibit sperm fertilization from a second wild-type male. Based on this, the release of excess B2t-null males significantly suppresses FAW populations. These results suggest that future development of genetic control techniques based on targeting nucleated sperm can effectively control FAW populations.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"85 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A linear ontogeny accounts for the development of naive, memory and tumour-infiltrating regulatory T cells in mice","authors":"Sanmoy Pathak, T. Hogan, S. Rane, Yundi Huang, Charles Sinclair, Simon Barry, Larissa Carnevalli, Andrew J Yates, Benedict Seddon","doi":"10.1101/2024.07.10.602914","DOIUrl":"https://doi.org/10.1101/2024.07.10.602914","url":null,"abstract":"Foxp3+ Regulatory T cells (Treg) are a subset of CD4+ T cells that play critical functions in maintaining tolerance to self antigens and suppressing autoimmunity, regulating immune responses to pathogens and have a role in the pathophysiology of anti-tumoural immunity. Treg ontogeny is complex since they are generated following recognition of self antigens in the thymus during normal T cell development (thymic Treg), but are also induced from mature conventional T cells when activated by foreign antigen with appropriate additional cues (inducible Treg). How these distinct ontogenic pathways contribute to the maintenance and function of the mature Treg compartment in health and disease remains unclear. Here, we use a combination of fate mapping approaches in mice to map the ontogeny of Treg subsets throughout life and estimate rates of production, loss and self-renewal. We find that naive and effector/memory (EM) Treg subsets exhibit distinct dynamics but are both continuously replenished by de novo generation throughout life. Using an inducible Foxp3-dependent Cre fate reporter system, we show that naive Treg and not conventional T cells, are the predominant precursors of EM Treg in adults. Tonic development of new EM Treg is not influenced by foreign antigens from commensals, rather suggesting a role for self recognition. To investigate the ontogeny of Treg development in malignant disease, we used the same fate reporter systems to characterise the Treg infiltrate of three different model tumours. In all three cases, we found that Treg derived from pre-existing, EM Treg. Together, these results reveal a predominantly linear pathway of Treg development from thymic origin to EM Treg associated with pathophysiology of malignant disease, that is driven by self antigen recognition throughout.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"58 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local keratinocyte-nociceptor interactions enhance obesity-mediated small fiber neuropathy via NGF-TrkA-PI3K signaling axis","authors":"Yuta Koui, Shuxuan Song, Xinzhong Dong, Y. Mukouyama","doi":"10.1101/2024.07.12.603316","DOIUrl":"https://doi.org/10.1101/2024.07.12.603316","url":null,"abstract":"The pathology of diabetic small fiber neuropathy, characterized by neuropathic pain and axon degeneration, develops locally within the skin during the stages of obesity and pre-diabetes. However, the initiation and progression of morphological and functional abnormalities in skin sensory nerves remains elusive. To address this, we utilized ear skin from mice with diet-induced obesity (DIO), the mouse models for obesity and pre-type 2 diabetes. We evaluated pain-associated wiping behavior and conducted ex vivo live Ca2+ imaging of the DIO ear skin to detect sensory hypersensitivity. Our findings reveal sensory hypersensitivity in skin nociceptive axons followed by axon degeneration. Further mechanistic analysis identified keratinocytes as a major source of nerve growth factor (NGF) in DIO skin, which locally sensitizes nociceptors through NGF-mediated signaling. Indeed, the local inactivation of NGF and its receptor TrkA-mediated downstream signaling, including the phosphoinositide 3-kinases (PI3K) pathway, suppresses sensory hypersensitivity in DIO skin. Thus, targeting these local interactions between keratinocytes and nociceptors offers a therapeutic strategy for managing neuropathic pain, avoiding the adverse effects associated with systemic interventions.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"10 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}