Pub Date : 2024-07-16DOI: 10.1101/2024.07.10.602932
S. Hosseini-Yazdi
Uneven terrain presents significant challenges for walkers, resulting in increased energy expenditures. Given that Center of Mass (COM) work reflects this energy demand, it's reasonable to assume that individuals also seek strategies to minimize mechanical work. One such strategy involves deciding between extending step length to avoid terrain irregularities or simply traversing over them. Each approach carries its own mechanical cost, leading to the adoption of the less costly option. To investigate this, we conducted a simulation focusing on COM mechanical work under the assumption that gait energy is entirely provided through pre-emptive push-off. We examined the COM work required for step length extension, ranging from nominal to twice its magnitude, and compared it with the mechanical work needed for step-ups from zero to 0.05 m. The simulation revealed a critical threshold for a given walking velocity and perturbation amplitude: below it, extending step length was more favorable, while beyond it, landing atop perturbations became the preferred choice. As perturbation amplitude rose, the magnitude of the threshold also increased.
不平坦的地形给步行者带来了巨大挑战，导致能量消耗增加。鉴于质量中心功（COM）反映了这种能量需求，我们可以合理地假设，步行者也在寻求尽量减少机械功的策略。其中一种策略就是在延长步长以避开不规则地形和简单穿越不规则地形之间做出选择。每种方法都会产生各自的机械成本，从而导致采用成本较低的方案。为了研究这个问题，我们进行了一次模拟，重点是在步态能量完全由先发制人的推力提供的假设下的 COM 机械功。我们研究了步长延长（从额定值到两倍）所需的COM功，并将其与步幅从0米到0.05米所需的机械功进行了比较。模拟结果表明，在给定的步行速度和扰动幅度下，存在一个临界阈值：低于该阈值时，步长延长更有利，而超过该阈值时，顶点着地扰动成为首选。随着扰动振幅的增加，临界值的大小也在增加。
{"title":"Uneven Walking is Challenging: step-ups or extended steps that is the question","authors":"S. Hosseini-Yazdi","doi":"10.1101/2024.07.10.602932","DOIUrl":"https://doi.org/10.1101/2024.07.10.602932","url":null,"abstract":"Uneven terrain presents significant challenges for walkers, resulting in increased energy expenditures. Given that Center of Mass (COM) work reflects this energy demand, it's reasonable to assume that individuals also seek strategies to minimize mechanical work. One such strategy involves deciding between extending step length to avoid terrain irregularities or simply traversing over them. Each approach carries its own mechanical cost, leading to the adoption of the less costly option. To investigate this, we conducted a simulation focusing on COM mechanical work under the assumption that gait energy is entirely provided through pre-emptive push-off. We examined the COM work required for step length extension, ranging from nominal to twice its magnitude, and compared it with the mechanical work needed for step-ups from zero to 0.05 m. The simulation revealed a critical threshold for a given walking velocity and perturbation amplitude: below it, extending step length was more favorable, while beyond it, landing atop perturbations became the preferred choice. As perturbation amplitude rose, the magnitude of the threshold also increased.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640603","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}
Aβ is believed to play a significant role in synaptic degeneration observed in Alzheimer’s disease (AD) and is primarily investigated as a secreted peptide. However, the contribution of intracellular Aβ or other cleavage products of its precursor protein (APP) to synaptic loss remains uncertain. In this study, we conducted a systematic examination of their cell-autonomous impact using a sparse expression system. Here, these proteins/peptides were overexpressed in a single neuron, surrounded by thousands of untransfected neurons. Surprisingly, we found that APP induced dendritic spine loss only when co-expressed with BACE1. This effect was mediated by β-CTF, a β-cleavage product of APP, through an endosome-related pathway independent of Aβ. Neuronal expression of β-CTF in mouse brains resulted in defective synaptic transmission and cognitive impairments, even in the absence of amyloid plaques. These findings unveil a β-CTF-initiated mechanism driving synaptic toxicity irrespective of amyloid plaque formation and suggest a potential intervention by inhibiting the endosomal GTPase Rab5.
{"title":"APP β-CTF triggers cell-autonomous synaptic toxicity independent of Aβ","authors":"Mengxun Luo, Jia Zhou, Cailu Sun, Wanjia Chen, Chaoying Fu, Chenfang Si, Yaoyang Zhang, Yang Geng, Yelin Chen","doi":"10.1101/2024.07.11.603028","DOIUrl":"https://doi.org/10.1101/2024.07.11.603028","url":null,"abstract":"Aβ is believed to play a significant role in synaptic degeneration observed in Alzheimer’s disease (AD) and is primarily investigated as a secreted peptide. However, the contribution of intracellular Aβ or other cleavage products of its precursor protein (APP) to synaptic loss remains uncertain. In this study, we conducted a systematic examination of their cell-autonomous impact using a sparse expression system. Here, these proteins/peptides were overexpressed in a single neuron, surrounded by thousands of untransfected neurons. Surprisingly, we found that APP induced dendritic spine loss only when co-expressed with BACE1. This effect was mediated by β-CTF, a β-cleavage product of APP, through an endosome-related pathway independent of Aβ. Neuronal expression of β-CTF in mouse brains resulted in defective synaptic transmission and cognitive impairments, even in the absence of amyloid plaques. These findings unveil a β-CTF-initiated mechanism driving synaptic toxicity irrespective of amyloid plaque formation and suggest a potential intervention by inhibiting the endosomal GTPase Rab5.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644144","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603075
Owen M. O’Connor, M. Dunlop
Deep learning-based methods for identifying and tracking cells within microscopy images have revolutionized the speed and throughput of data analysis. These methods for analyzing biological and medical data have capitalized on advances from the broader computer vision field. However, cell tracking can present unique challenges, with frequent cell division events and the need to track many objects with similar visual appearances complicating analysis. Existing architectures developed for cell tracking based on convolutional neural networks (CNNs) have tended to fall short in managing the spatial and global contextual dependencies that are crucial for tracking cells. To overcome these limitations, we introduce Cell-TRACTR (Transformer with Attention for Cell Tracking and Recognition), a novel deep learning model that uses a transformer-based architecture. The attention mechanism inherent in transformers facilitates long-range connections, effectively linking features across different spatial regions, which is critical for robust cell tracking. Cell-TRACTR operates in an end-to-end manner, simultaneously segmenting and tracking cells without the need for post-processing. Alongside this model, we introduce the Cell-HOTA metric, an extension of the Higher Order Tracking Accuracy (HOTA) metric that we adapted to assess cell division. Cell-HOTA differs from standard cell tracking metrics by offering a balanced and easily interpretable assessment of detection, association, and division accuracy. We test our Cell-TRACTR model on datasets of bacteria growing within a defined microfluidic geometry and mammalian cells growing freely in two dimensions. Our results demonstrate that Cell-TRACTR exhibits excellent performance in tracking and division accuracy compared to state-of-the-art algorithms, while also matching traditional benchmarks in detection accuracy. This work establishes a new framework for employing transformer-based models in cell segmentation and tracking. Author Summary Understanding the growth, movement, and gene expression dynamics of individual cells is critical for studies in a wide range of areas, from antibiotic resistance to cancer. Monitoring individual cells can reveal unique insights that are obscured by population averages. Although modern microscopy techniques have vastly improved researchers’ ability to collect data, tracking individual cells over time remains a challenge, particularly due to complexities such as cell division and non-linear cell movements. To address this, we developed a new transformer-based model called Cell-TRACTR that can segment and track single cells without the need for post-processing. The strength of the transformer architecture lies in its attention mechanism, which integrates global context. Attention makes this model particularly well suited for tracking cells across a sequence of images. In addition to the Cell-TRACTR model, we introduce a new metric, Cell-HOTA, to evaluate tracking algorithms in ter
{"title":"Cell-TRACTR: A transformer-based model for end-to-end segmentation and tracking of cells","authors":"Owen M. O’Connor, M. Dunlop","doi":"10.1101/2024.07.11.603075","DOIUrl":"https://doi.org/10.1101/2024.07.11.603075","url":null,"abstract":"Deep learning-based methods for identifying and tracking cells within microscopy images have revolutionized the speed and throughput of data analysis. These methods for analyzing biological and medical data have capitalized on advances from the broader computer vision field. However, cell tracking can present unique challenges, with frequent cell division events and the need to track many objects with similar visual appearances complicating analysis. Existing architectures developed for cell tracking based on convolutional neural networks (CNNs) have tended to fall short in managing the spatial and global contextual dependencies that are crucial for tracking cells. To overcome these limitations, we introduce Cell-TRACTR (Transformer with Attention for Cell Tracking and Recognition), a novel deep learning model that uses a transformer-based architecture. The attention mechanism inherent in transformers facilitates long-range connections, effectively linking features across different spatial regions, which is critical for robust cell tracking. Cell-TRACTR operates in an end-to-end manner, simultaneously segmenting and tracking cells without the need for post-processing. Alongside this model, we introduce the Cell-HOTA metric, an extension of the Higher Order Tracking Accuracy (HOTA) metric that we adapted to assess cell division. Cell-HOTA differs from standard cell tracking metrics by offering a balanced and easily interpretable assessment of detection, association, and division accuracy. We test our Cell-TRACTR model on datasets of bacteria growing within a defined microfluidic geometry and mammalian cells growing freely in two dimensions. Our results demonstrate that Cell-TRACTR exhibits excellent performance in tracking and division accuracy compared to state-of-the-art algorithms, while also matching traditional benchmarks in detection accuracy. This work establishes a new framework for employing transformer-based models in cell segmentation and tracking. Author Summary Understanding the growth, movement, and gene expression dynamics of individual cells is critical for studies in a wide range of areas, from antibiotic resistance to cancer. Monitoring individual cells can reveal unique insights that are obscured by population averages. Although modern microscopy techniques have vastly improved researchers’ ability to collect data, tracking individual cells over time remains a challenge, particularly due to complexities such as cell division and non-linear cell movements. To address this, we developed a new transformer-based model called Cell-TRACTR that can segment and track single cells without the need for post-processing. The strength of the transformer architecture lies in its attention mechanism, which integrates global context. Attention makes this model particularly well suited for tracking cells across a sequence of images. In addition to the Cell-TRACTR model, we introduce a new metric, Cell-HOTA, to evaluate tracking algorithms in ter","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644291","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603179
L. Couturier, Juan C. Luna-Escalante, Khallil Mazouni, Claire Mestdagh, Minh-Son Phan, J. Tinevez, François Schweisguth, Francis Corson
Pattern formation in developing tissues often involves self-organization guided by positional information. In most tissues, however, its dynamics, and therefore the underlying logic, remain unknown. Examining self-organized patterning of the fly eye, we combine experiments and modeling to elucidate how rows of light-receiving units emerge in the wake of a traveling differentiation front to form a crystal-like array. Live imaging of the proneural factor Atonal reveals unanticipated oscillations at the front, which are produced by the successive activation of two distinct enhancers and associated with pulsatile Notch signaling. Our observations are inconsistent with current models of eye patterning, whereby each row of differentiating cells provides a negative template for the next. Instead, they inform a new relay model in which transient Notch signaling from differentiating cells provides a positive template for the onset of differentiation two rows ahead, conveying both temporal and spatial information to propagate oscillations and crystal-like order.
{"title":"Pulsatile dynamics propagate crystalline order in the developing Drosophila eye","authors":"L. Couturier, Juan C. Luna-Escalante, Khallil Mazouni, Claire Mestdagh, Minh-Son Phan, J. Tinevez, François Schweisguth, Francis Corson","doi":"10.1101/2024.07.11.603179","DOIUrl":"https://doi.org/10.1101/2024.07.11.603179","url":null,"abstract":"Pattern formation in developing tissues often involves self-organization guided by positional information. In most tissues, however, its dynamics, and therefore the underlying logic, remain unknown. Examining self-organized patterning of the fly eye, we combine experiments and modeling to elucidate how rows of light-receiving units emerge in the wake of a traveling differentiation front to form a crystal-like array. Live imaging of the proneural factor Atonal reveals unanticipated oscillations at the front, which are produced by the successive activation of two distinct enhancers and associated with pulsatile Notch signaling. Our observations are inconsistent with current models of eye patterning, whereby each row of differentiating cells provides a negative template for the next. Instead, they inform a new relay model in which transient Notch signaling from differentiating cells provides a positive template for the onset of differentiation two rows ahead, conveying both temporal and spatial information to propagate oscillations and crystal-like order.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642443","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603127
Michael J Wenger, James T. Townsend, Sarah F. Newbolds
We propose an indirect measure of the efficiency of neural processing: the neural efficiency score (NES). The basis for this measure is the hazard function on the reaction time distribution from a task, h(t), which can be interpreted as an instantaneous measure of work being accomplished, and which has been foundational in characterizations of perceptual and cognitive workload capacity (e.g., Townsend & Ashby, 1978; Townsend & Nozawa, 1995; Townsend & Wenger, 2004). We suggest that the global field power on electroencephalographic (EEG) data (Skrandies, 1989, 1990) can function as a proxy for actual energy expended, and then place h(t) and GFP in a ratio to give a measure that can be interpreted as work accomplished relative to energy expended. To make this proposal plausible, we first need to show that the GFP can be interpreted in terms of energy expended, and we do this using previously unpublished data from an earlier study (Wenger, DellaValle, Murray-Kolb, & Haas, 2017) in which we simultaneously collected EEG and metabolic data during the performance of a cognitive task. Having shown that the GFP can be used as a proxy for energy expended, we then demonstrate the interpretability of the NES by applying it to previously unpublished data from a more recent study (Newbolds & Wenger, 2024). These outcomes suggest the potential for broad applicability of the NES and its potential for characterizing the efficiency of neural energy expenditure in the performance of perceptual and cognitive work.
{"title":"The Neural efficiency score: Validation and application","authors":"Michael J Wenger, James T. Townsend, Sarah F. Newbolds","doi":"10.1101/2024.07.11.603127","DOIUrl":"https://doi.org/10.1101/2024.07.11.603127","url":null,"abstract":"We propose an indirect measure of the efficiency of neural processing: the neural efficiency score (NES). The basis for this measure is the hazard function on the reaction time distribution from a task, h(t), which can be interpreted as an instantaneous measure of work being accomplished, and which has been foundational in characterizations of perceptual and cognitive workload capacity (e.g., Townsend & Ashby, 1978; Townsend & Nozawa, 1995; Townsend & Wenger, 2004). We suggest that the global field power on electroencephalographic (EEG) data (Skrandies, 1989, 1990) can function as a proxy for actual energy expended, and then place h(t) and GFP in a ratio to give a measure that can be interpreted as work accomplished relative to energy expended. To make this proposal plausible, we first need to show that the GFP can be interpreted in terms of energy expended, and we do this using previously unpublished data from an earlier study (Wenger, DellaValle, Murray-Kolb, & Haas, 2017) in which we simultaneously collected EEG and metabolic data during the performance of a cognitive task. Having shown that the GFP can be used as a proxy for energy expended, we then demonstrate the interpretability of the NES by applying it to previously unpublished data from a more recent study (Newbolds & Wenger, 2024). These outcomes suggest the potential for broad applicability of the NES and its potential for characterizing the efficiency of neural energy expenditure in the performance of perceptual and cognitive work.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642808","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.12.603182
R. Walk, Kaitlyn S. Broz, L. Jing, Ryan P. Potter, Alec T. Beeve, Erica L. Scheller, Munish C. Gupta, Lori A. Setton, Simon Y. Tang
The accessibility of the mouse caudal intervertebral disc (IVD) and its geometric semblance to the human IVD makes it an attractive model for assessing IVD-specific responses in vivo. To effectively utilize this model, the temporal trajectories of key pathoanatomical features, such as the production of inflammatory chemokines, tissue disorganization, and neo-vessel and neurite infiltration, must be understood. This study aims to define the progression of chemokine production and neurovascular invasion at 2-, 4-, and 12-weeks following a caudal IVD injury in 3-month-old female C57BL6/J mice. We measured IVD-secreted chemokines and matrix metalloproteinases (MMPs) using multiplex ELISA, graded the histopathological degeneration, and quantified the intradiscal infiltrating vessels (endomucin) and nerves (protein-gene-product 9.5) using immunohistochemistry. Injury provoked the secretion of IL6, CCL2, CCL12, CCL17, CCL20, CCL21, CCL22, CXCL2 and MMP2 proteins. Neurites propagated rapidly within 2-weeks post-injury and remained relatively constant until 12-weeks. Peak vascular vessel length occurred at 4-weeks post-injury and regressed by 12-weeks. These findings identified the temporal flux of inflammatory chemokines and pain-associated pathoanatomy in a model of IVD degeneration using the mouse caudal spine.
{"title":"The progression of infiltrating neurovascular features and chemokine production of the caudal intervertebral disc following injury","authors":"R. Walk, Kaitlyn S. Broz, L. Jing, Ryan P. Potter, Alec T. Beeve, Erica L. Scheller, Munish C. Gupta, Lori A. Setton, Simon Y. Tang","doi":"10.1101/2024.07.12.603182","DOIUrl":"https://doi.org/10.1101/2024.07.12.603182","url":null,"abstract":"The accessibility of the mouse caudal intervertebral disc (IVD) and its geometric semblance to the human IVD makes it an attractive model for assessing IVD-specific responses in vivo. To effectively utilize this model, the temporal trajectories of key pathoanatomical features, such as the production of inflammatory chemokines, tissue disorganization, and neo-vessel and neurite infiltration, must be understood. This study aims to define the progression of chemokine production and neurovascular invasion at 2-, 4-, and 12-weeks following a caudal IVD injury in 3-month-old female C57BL6/J mice. We measured IVD-secreted chemokines and matrix metalloproteinases (MMPs) using multiplex ELISA, graded the histopathological degeneration, and quantified the intradiscal infiltrating vessels (endomucin) and nerves (protein-gene-product 9.5) using immunohistochemistry. Injury provoked the secretion of IL6, CCL2, CCL12, CCL17, CCL20, CCL21, CCL22, CXCL2 and MMP2 proteins. Neurites propagated rapidly within 2-weeks post-injury and remained relatively constant until 12-weeks. Peak vascular vessel length occurred at 4-weeks post-injury and regressed by 12-weeks. These findings identified the temporal flux of inflammatory chemokines and pain-associated pathoanatomy in a model of IVD degeneration using the mouse caudal spine.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642080","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.11.603117
Jose Inacio Costa-Filho, Liam Theveny, Marilina de Sautu, Tom Kirchhausen
Cryogenic electron tomography (cryo-ET) has rapidly advanced as a high-resolution imaging tool for visualizing subcellular structures in 3D with molecular detail. Direct image inspection remains challenging due to inherent low signal-to-noise ratios (SNR). We introduce CryoSamba, a self-supervised deep learning-based model designed for denoising cryo-ET images. CryoSamba enhances single consecutive 2D planes in tomograms by averaging motion-compensated nearby planes through deep learning interpolation, effectively mimicking increased exposure. This approach amplifies coherent signals and reduces high-frequency noise, substantially improving tomogram contrast and SNR. CryoSamba operates on 3D volumes without needing pre-recorded images, synthetic data, labels or annotations, noise models, or paired volumes. CryoSamba suppresses high-frequency information less aggressively than do existing cryo-ET denoising methods, while retaining real information, as shown both by visual inspection and by Fourier shell correlation analysis of icosahedrally symmetric virus particles. Thus, CryoSamba enhances the analytical pipeline for direct 3D tomogram visual interpretation.
{"title":"CryoSamba: self-supervised deep volumetric denoising for cryo-electron tomography data","authors":"Jose Inacio Costa-Filho, Liam Theveny, Marilina de Sautu, Tom Kirchhausen","doi":"10.1101/2024.07.11.603117","DOIUrl":"https://doi.org/10.1101/2024.07.11.603117","url":null,"abstract":"Cryogenic electron tomography (cryo-ET) has rapidly advanced as a high-resolution imaging tool for visualizing subcellular structures in 3D with molecular detail. Direct image inspection remains challenging due to inherent low signal-to-noise ratios (SNR). We introduce CryoSamba, a self-supervised deep learning-based model designed for denoising cryo-ET images. CryoSamba enhances single consecutive 2D planes in tomograms by averaging motion-compensated nearby planes through deep learning interpolation, effectively mimicking increased exposure. This approach amplifies coherent signals and reduces high-frequency noise, substantially improving tomogram contrast and SNR. CryoSamba operates on 3D volumes without needing pre-recorded images, synthetic data, labels or annotations, noise models, or paired volumes. CryoSamba suppresses high-frequency information less aggressively than do existing cryo-ET denoising methods, while retaining real information, as shown both by visual inspection and by Fourier shell correlation analysis of icosahedrally symmetric virus particles. Thus, CryoSamba enhances the analytical pipeline for direct 3D tomogram visual interpretation.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640771","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.12.603327
Zsófia Varga-Szilay, A. Barševskis, Klára Benedek, Danilo Bevk, A. Jojczyk, Anton Krištín, J. Růžičková, L. S. Jelaska, Eve Veromann, Silva Vilumets, K. Fetykó, G. Szövényi, Gábor Pozsgai
Amid ongoing urbanisation and increasing anthropogenic activities, domestic gardens, while cannot replace natural habitats, play a crucial role in enhancing urban biodiversity by supporting green areas and as parts of ecological corridors. Moreover, these biodiversity-friendly gardens also improve human well-being and foster a connection between nature and people. We circulated an online questionnaire between 2022 and 2023 to investigate how the garden parameters, the gardening motivation of garden owners, and their pesticide use habits depend on each other in nine Central– and Eastern European (CEE) countries. Moreover, we aimed to explore the differences and similarities between gardens and gardening practices with a potential for maintaining high biodiversity. To achieve this, we assessed the ecological value of the gardens, the motivation of garden owners, and their pesticide use habits using an answer-based scoring system. Our findings reveal significant variability both among participating countries and within them on a smaller and larger scale, across all three indices, highlighting the need for region-specific circumstances rather than unified regulations across European countries to maximize the conservation value examined. Our study underscores the potential of domestic gardens in designing eco-networks and informs strategies to optimize their environmental benefits. However, due to the ubiquitous domestic use of pesticides in CEE, informing garden owners about the environmental and human health effects of pesticides would be equally necessary in every area, both urban and rural. Additionally, our findings suggest that effective environmental educational programs and tailored strategies should be developed to meet local needs rather than overarching but too general international targets. At the same time, these programs should provide comprehensive biodiversity-related information, reaching all strata of society. This is especially important in CEE, where such initiatives are currently under-emphasized.
{"title":"Improving biodiversity in Central and Eastern European domestic gardens needs regionally scaled strategies","authors":"Zsófia Varga-Szilay, A. Barševskis, Klára Benedek, Danilo Bevk, A. Jojczyk, Anton Krištín, J. Růžičková, L. S. Jelaska, Eve Veromann, Silva Vilumets, K. Fetykó, G. Szövényi, Gábor Pozsgai","doi":"10.1101/2024.07.12.603327","DOIUrl":"https://doi.org/10.1101/2024.07.12.603327","url":null,"abstract":"Amid ongoing urbanisation and increasing anthropogenic activities, domestic gardens, while cannot replace natural habitats, play a crucial role in enhancing urban biodiversity by supporting green areas and as parts of ecological corridors. Moreover, these biodiversity-friendly gardens also improve human well-being and foster a connection between nature and people. We circulated an online questionnaire between 2022 and 2023 to investigate how the garden parameters, the gardening motivation of garden owners, and their pesticide use habits depend on each other in nine Central– and Eastern European (CEE) countries. Moreover, we aimed to explore the differences and similarities between gardens and gardening practices with a potential for maintaining high biodiversity. To achieve this, we assessed the ecological value of the gardens, the motivation of garden owners, and their pesticide use habits using an answer-based scoring system. Our findings reveal significant variability both among participating countries and within them on a smaller and larger scale, across all three indices, highlighting the need for region-specific circumstances rather than unified regulations across European countries to maximize the conservation value examined. Our study underscores the potential of domestic gardens in designing eco-networks and informs strategies to optimize their environmental benefits. However, due to the ubiquitous domestic use of pesticides in CEE, informing garden owners about the environmental and human health effects of pesticides would be equally necessary in every area, both urban and rural. Additionally, our findings suggest that effective environmental educational programs and tailored strategies should be developed to meet local needs rather than overarching but too general international targets. At the same time, these programs should provide comprehensive biodiversity-related information, reaching all strata of society. This is especially important in CEE, where such initiatives are currently under-emphasized.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641900","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}
Pub Date : 2024-07-16DOI: 10.1101/2024.07.12.603090
Kai Shimagaki, Rebecca M. Lynch, J. Barton
Human immunodeficiency virus (HIV)-1 exhibits remarkable genetic diversity. For this reason, an effective HIV-1 vaccine must elicit antibodies that can neutralize many variants of the virus. While broadly neutralizing antibodies (bnAbs) have been isolated from HIV-1 infected individuals, a general understanding of the virus-antibody coevolutionary processes that lead to their development remains incomplete. We performed a quantitative study of HIV-1 evolution in two individuals who developed bnAbs. We observed strong selection early in infection for mutations affecting HIV-1 envelope glycosylation and escape from autologous strain-specific antibodies, followed by weaker selection for bnAb resistance later in infection. To confirm our findings, we analyzed data from rhesus macaques infected with viruses derived from the same two individuals. We inferred remarkably similar fitness effects of HIV-1 mutations in humans and macaques. Moreover, we observed a striking pattern of rapid HIV-1 evolution, consistent in both humans and macaques, that precedes the development of bnAbs. Our work highlights strong parallels between infection in rhesus macaques and humans, and it reveals a quantitative evolutionary signature of bnAb development.
{"title":"Parallel HIV-1 evolutionary dynamics in humans and rhesus macaques who develop broadly neutralizing antibodies","authors":"Kai Shimagaki, Rebecca M. Lynch, J. Barton","doi":"10.1101/2024.07.12.603090","DOIUrl":"https://doi.org/10.1101/2024.07.12.603090","url":null,"abstract":"Human immunodeficiency virus (HIV)-1 exhibits remarkable genetic diversity. For this reason, an effective HIV-1 vaccine must elicit antibodies that can neutralize many variants of the virus. While broadly neutralizing antibodies (bnAbs) have been isolated from HIV-1 infected individuals, a general understanding of the virus-antibody coevolutionary processes that lead to their development remains incomplete. We performed a quantitative study of HIV-1 evolution in two individuals who developed bnAbs. We observed strong selection early in infection for mutations affecting HIV-1 envelope glycosylation and escape from autologous strain-specific antibodies, followed by weaker selection for bnAb resistance later in infection. To confirm our findings, we analyzed data from rhesus macaques infected with viruses derived from the same two individuals. We inferred remarkably similar fitness effects of HIV-1 mutations in humans and macaques. Moreover, we observed a striking pattern of rapid HIV-1 evolution, consistent in both humans and macaques, that precedes the development of bnAbs. Our work highlights strong parallels between infection in rhesus macaques and humans, and it reveals a quantitative evolutionary signature of bnAb development.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641076","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}
Background: A century ago, a mystery between virus and Parkinson’s disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly-developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantial nigra (SN), and whether symbiotic viruses underlie PD pathogenesis remain unknown. Methods: We collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands and Switzerland. We used bioinformatic approaches including viruSITE and the Virus-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearson’s correlation analysis was used to examine the association between the viral RNA fragment counts (VRFC) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. Findings: We observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A significant correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified three bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174 and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the UK, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken cGAS-STING function. Interpretation: This is the first study to discover the involvement of phages in PD pathogenesis. A life-long low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phages-human symbiosis.
背景：一个世纪前，病毒与帕金森病（PD）之间的神秘关系被描述出来。由于人脑活检的局限性和电子显微镜观察人脑组织中病毒的挑战性，研究帕金森病的病毒病因一直很困难。最近发现的病毒生物群揭示了病毒作为共生体与人类共存。新开发的转录组测序技术和挖掘人类转录组中加密病毒组的新型生物信息学方法使研究共生病毒与帕金森病之间的关系成为可能。然而，病毒是否存在于人类黑质（SN）中，以及共生病毒是否是白内障发病机制的基础仍是未知数。方法：我们从美国、英国、荷兰和瑞士收集了当前全球人类SN转录组数据集。我们使用生物信息学方法（包括 viruSITE 和 Virus-Track）来确定患者 SN 中是否存在病毒。基于 RNA 测序的病毒组综合分析管道用于描述 SN 中的病毒生物群特征。皮尔逊相关性分析用于研究SN中病毒RNA片段计数（VRFC）与PD相关人类基因测序读数之间的关联。利用腹股沟淋巴结核患者与非腹股沟淋巴结核患者之间的差异表达基因（DEGs）来研究腹股沟淋巴结核的分子特征，同时评估共生病毒对腹股沟淋巴结核的影响。研究结果我们观察到人类SN中存在病毒。在帕金森氏症患者的SN中发现了病毒群的菌群失调。在帕金森氏症患者的SN中发现了VRFC与帕金森氏症相关人类基因表达之间的明显相关性。这些与 VRFC 相关的 PD 相关人类基因被命名为与病毒相关的 PD 相关基因（VPGs）。我们发现了三种噬菌体（包括变形杆菌噬菌体VB_PmiS-Isfahan、埃希氏菌噬菌体phiX174和乳酸杆菌噬菌体Sha1）可能会损害PD患者SN中神经细胞的基因表达。变形杆菌噬菌体VB_PmiS-Isfahan是英国、荷兰和瑞士患者SN中的常见病毒。VPGs和DEGs共同表明，噬菌体可能会抑制多巴胺的生物合成并削弱cGAS-STING的功能。解读：这是首次发现噬菌体参与帕金森病发病机制的研究。SN中终生低共生病毒载量可能是导致帕金森病发病的一个因素。我们的研究结果揭开了脑部生物群与帕金森病之间的黑匣子，从噬菌体与人类共生的角度为帕金森病的病因学提供了新的见解。
{"title":"The discovery of phages in the Substantia Nigra and its implication for Parkinson’s Disease","authors":"Yun Zhao, Changxian Xiong, Bingwei Wang, Daotong Li, Jiarui Liu, Shizhang Wei, Yujia Hou, Yuan Zhou, Ruimao Zheng","doi":"10.1101/2024.07.13.603353","DOIUrl":"https://doi.org/10.1101/2024.07.13.603353","url":null,"abstract":"Background: A century ago, a mystery between virus and Parkinson’s disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly-developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantial nigra (SN), and whether symbiotic viruses underlie PD pathogenesis remain unknown. Methods: We collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands and Switzerland. We used bioinformatic approaches including viruSITE and the Virus-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearson’s correlation analysis was used to examine the association between the viral RNA fragment counts (VRFC) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. Findings: We observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A significant correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified three bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174 and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the UK, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken cGAS-STING function. Interpretation: This is the first study to discover the involvement of phages in PD pathogenesis. A life-long low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phages-human symbiosis.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642602","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}
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