Pub Date : 2024-08-08DOI: 10.1101/2024.08.06.606757
Ann-Kathrin Dörr, Josefa Welling, Adrian Dörr, Jule Gosch, Hannah Möhlen, Ricarda M. Schmithausen, J. Kehrmann, Folker Meyer, I. Kraiselburd
Background Next-generation sequencing for assaying microbial communities has become a standard technique in recent years. However, the initial investment required into in-silico analytics is still quite significant, especially for facilities not focused on bioinformatics. With the rapid decline in costs and growing adoption of sequencing-based methods in a number of fields, validated, fully automated, reproducible and yet flexible pipelines will play a greater role in various scientific fields in the future. Results We present RiboSnake, a validated, automated, reproducible QIIME2-based analysis pipeline implemented in Snakemake for the computational analysis of 16S rRNA gene amplicon sequencing data. The pipeline comes with pre-packaged validated parameter sets, optimized for different sample types. The sets range from complex environmental samples to patient data. The configuration packages can be easily adapted and shared, requiring minimal user input. Conclusion RiboSnake is a new alternative for researchers employing 16S rRNA gene amplicon sequencing and looking for a customizable and yet user-friendly pipeline for microbiome analysis with in-vitro validated settings. The complete analysis generated with a fully automated pipeline based on validated parameter sets for different sample types is a significant improvement to existing methods. The workflow repository can be found on GitHub (https://github.com/IKIM-Essen/RiboSnake).
{"title":"RiboSnake – a user-friendly, robust, reproducible, multipurpose and documentation-extensive pipeline for 16S rRNA gene microbiome analysis","authors":"Ann-Kathrin Dörr, Josefa Welling, Adrian Dörr, Jule Gosch, Hannah Möhlen, Ricarda M. Schmithausen, J. Kehrmann, Folker Meyer, I. Kraiselburd","doi":"10.1101/2024.08.06.606757","DOIUrl":"https://doi.org/10.1101/2024.08.06.606757","url":null,"abstract":"Background Next-generation sequencing for assaying microbial communities has become a standard technique in recent years. However, the initial investment required into in-silico analytics is still quite significant, especially for facilities not focused on bioinformatics. With the rapid decline in costs and growing adoption of sequencing-based methods in a number of fields, validated, fully automated, reproducible and yet flexible pipelines will play a greater role in various scientific fields in the future. Results We present RiboSnake, a validated, automated, reproducible QIIME2-based analysis pipeline implemented in Snakemake for the computational analysis of 16S rRNA gene amplicon sequencing data. The pipeline comes with pre-packaged validated parameter sets, optimized for different sample types. The sets range from complex environmental samples to patient data. The configuration packages can be easily adapted and shared, requiring minimal user input. Conclusion RiboSnake is a new alternative for researchers employing 16S rRNA gene amplicon sequencing and looking for a customizable and yet user-friendly pipeline for microbiome analysis with in-vitro validated settings. The complete analysis generated with a fully automated pipeline based on validated parameter sets for different sample types is a significant improvement to existing methods. The workflow repository can be found on GitHub (https://github.com/IKIM-Essen/RiboSnake).","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"26 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141925753","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}
The peony of Sect. Paeonia was a perennial herbaceous plant with numerous ornamental varieties and riched diversity in flower color and shape. It has ornamental, edible, and medicinal value and a long history of cultivation in China. The study of phenotypic diversity of plants is an important foundation for plants of Sect. Paeonia breeding. This study conducted phenotypic diversity analysis, principal component analysis, and cluster analysis on 43 varieties of Sect. Paeonia germplasm resources. Phenotypic traits included 30 qualitative traits and 7 quantitative traits. Through genetic diversity analysis, principal component analysis, comprehensive evaluation, and cluster analysis, we ultimately concluded that plant samples had relatively rich genetic phenotype traits. In principal component analysis, the first 12 principal components have covered the vast majority of information for phenotypic traits. The comprehensive evaluation results of phenotypic traits indicate that the F values of each variety in the germplasm sample were all positive number. The degree of stamen petals played a key role in determining the phenotypic diversity of plants, and the shape of the cotyledons and leaflets may determine the plant’s stress resistance performance, which provides a reference for breeding new varieties of peonies of Sect. Paeonia.
{"title":"Study on the phenotypic diversity and comprehensive evaluation analysis of 43 ornamental peonies of Sect. Paeonia","authors":"Hui-yan Cao, Shi-yi Xu, Meiqi Liu, Shan Jiang, Lengleng Ma, Jian-hao Wu, Xiao-Zhuang Zhang, Ling-yang Kong, Weichhao Ren, Zhi-yang Liu, Xi Chen, Wei Ma, X. Liu","doi":"10.1101/2024.08.06.606934","DOIUrl":"https://doi.org/10.1101/2024.08.06.606934","url":null,"abstract":"The peony of Sect. Paeonia was a perennial herbaceous plant with numerous ornamental varieties and riched diversity in flower color and shape. It has ornamental, edible, and medicinal value and a long history of cultivation in China. The study of phenotypic diversity of plants is an important foundation for plants of Sect. Paeonia breeding. This study conducted phenotypic diversity analysis, principal component analysis, and cluster analysis on 43 varieties of Sect. Paeonia germplasm resources. Phenotypic traits included 30 qualitative traits and 7 quantitative traits. Through genetic diversity analysis, principal component analysis, comprehensive evaluation, and cluster analysis, we ultimately concluded that plant samples had relatively rich genetic phenotype traits. In principal component analysis, the first 12 principal components have covered the vast majority of information for phenotypic traits. The comprehensive evaluation results of phenotypic traits indicate that the F values of each variety in the germplasm sample were all positive number. The degree of stamen petals played a key role in determining the phenotypic diversity of plants, and the shape of the cotyledons and leaflets may determine the plant’s stress resistance performance, which provides a reference for breeding new varieties of peonies of Sect. Paeonia.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"19 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927272","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 : 2024-08-08DOI: 10.1101/2024.08.06.606712
Abdulraouf Abdulraouf, Weirong Jiang, Zihan Xu, Zehao Zhang, Samuel Isakov, Tanvir Raihan, Wei Zhou, Junyue Cao
Spatial transcriptomics has revolutionized our understanding of cellular network dynamics in aging and disease by enabling the mapping of molecular and cellular organization across various anatomical locations. Despite these advances, current methods face significant challenges in throughput and cost, limiting their utility for comprehensive studies. To address these limitations, we introduce IRISeq (Imaging Reconstruction using Indexed Sequencing), a optics-free spatial transcriptomics platform that eliminates the need for predefined capture arrays or extensive imaging, allowing for the rapid and cost-effective processing of multiple tissue sections simultaneously. Its capacity to reconstruct images based solely on sequencing local DNA interactions allows for profiling of tissues without size constraints and across varied resolutions. Applying IRISeq, we examined gene expression and cellular dynamics in thirty brain regions of both adult and aged mice, uncovering region-specific changes in gene expression associated with aging. Further cell type-centric analysis further identified age-related cell subtypes and intricate changes in cell interactions that are distinct to certain spatial niches, emphasizing the unique aspects of aging in different brain regions. The affordability and simplicity of IRISeq position it as a versatile tool for mapping region-specific gene expression and cellular interactions across various biological systems. One Sentence Summary: IRISeq, an innovative optics-free spatial transcriptomics method, uncovers aging-related changes in spatial gene expression and focal cell interactions in brain aging.
空间转录组学通过绘制不同解剖位置的分子和细胞组织图，彻底改变了我们对衰老和疾病中细胞网络动态的理解。尽管取得了这些进展，但目前的方法在通量和成本方面仍面临巨大挑战，限制了它们在综合研究中的应用。为了解决这些局限性，我们推出了 IRISeq（使用索引测序的成像重建），这是一种无光学器件的空间转录组学平台，无需预定义的捕获阵列或大量成像，可同时快速、经济高效地处理多个组织切片。它能仅根据局部 DNA 相互作用的测序结果重建图像，因此可以不受尺寸限制地对不同分辨率的组织进行分析。应用 IRISeq，我们检测了成年小鼠和老年小鼠 30 个脑区的基因表达和细胞动态，发现了与衰老相关的特定区域基因表达变化。以细胞类型为中心的进一步分析进一步确定了与年龄相关的细胞亚型和细胞相互作用的复杂变化，这些变化与特定的空间壁龛不同，强调了不同脑区衰老的独特方面。IRISeq 价格低廉、操作简单，是绘制各种生物系统中特定区域基因表达和细胞相互作用图谱的多功能工具。一句话总结：IRISeq 是一种创新的免光学空间转录组学方法，它揭示了大脑衰老过程中与衰老相关的空间基因表达和病灶细胞相互作用的变化。
{"title":"Optics-free Spatial Genomics for Mapping Mouse Brain Aging","authors":"Abdulraouf Abdulraouf, Weirong Jiang, Zihan Xu, Zehao Zhang, Samuel Isakov, Tanvir Raihan, Wei Zhou, Junyue Cao","doi":"10.1101/2024.08.06.606712","DOIUrl":"https://doi.org/10.1101/2024.08.06.606712","url":null,"abstract":"Spatial transcriptomics has revolutionized our understanding of cellular network dynamics in aging and disease by enabling the mapping of molecular and cellular organization across various anatomical locations. Despite these advances, current methods face significant challenges in throughput and cost, limiting their utility for comprehensive studies. To address these limitations, we introduce IRISeq (Imaging Reconstruction using Indexed Sequencing), a optics-free spatial transcriptomics platform that eliminates the need for predefined capture arrays or extensive imaging, allowing for the rapid and cost-effective processing of multiple tissue sections simultaneously. Its capacity to reconstruct images based solely on sequencing local DNA interactions allows for profiling of tissues without size constraints and across varied resolutions. Applying IRISeq, we examined gene expression and cellular dynamics in thirty brain regions of both adult and aged mice, uncovering region-specific changes in gene expression associated with aging. Further cell type-centric analysis further identified age-related cell subtypes and intricate changes in cell interactions that are distinct to certain spatial niches, emphasizing the unique aspects of aging in different brain regions. The affordability and simplicity of IRISeq position it as a versatile tool for mapping region-specific gene expression and cellular interactions across various biological systems. One Sentence Summary: IRISeq, an innovative optics-free spatial transcriptomics method, uncovers aging-related changes in spatial gene expression and focal cell interactions in brain aging.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"46 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927965","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 : 2024-08-08DOI: 10.1101/2024.08.07.606811
Jean-François De Backer, Thomas Karges, Julia Papst, Cristina Coman, R. Ahrends, Yanjun Xu, C. García-Cáceres, Ilona C. Grunwald Kadow
An animal’s metabolic state strongly influences its behavior. Hungry animals prioritize food seeking and feeding behaviors, while sated animals suppress these behaviors to engage in other activities. Additionally, neuronal activity and synaptic transmission are among the most energy expensive processes. Yet neurons do not uptake nutrients from the circulation. Instead, glia fulfill this highly evolutionary conserved function. Recent studies have shown that glia can modulate neuronal activity and behavior. However, how different glia subtypes sense metabolic state and modulate neurons and behavior is incompletely understood. Here, we unravel two types of glia-mediated modulation of metabolic state-dependent behavior. In food-deprived flies, astrocyte-like and perineurial glia promote foraging and feeding, respectively, while cortex glia suppress these behaviors. We further show that adenosine and adenosine receptor modulate intracellular calcium levels in these glia subtypes, which ultimately controls behavior. This study reveals a new mechanism how different glia subtypes sense the metabolic state of the animal and modulate its behavior accordingly.
{"title":"Adenosine signaling in glia modulates metabolic state-dependent behavior in Drosophila","authors":"Jean-François De Backer, Thomas Karges, Julia Papst, Cristina Coman, R. Ahrends, Yanjun Xu, C. García-Cáceres, Ilona C. Grunwald Kadow","doi":"10.1101/2024.08.07.606811","DOIUrl":"https://doi.org/10.1101/2024.08.07.606811","url":null,"abstract":"An animal’s metabolic state strongly influences its behavior. Hungry animals prioritize food seeking and feeding behaviors, while sated animals suppress these behaviors to engage in other activities. Additionally, neuronal activity and synaptic transmission are among the most energy expensive processes. Yet neurons do not uptake nutrients from the circulation. Instead, glia fulfill this highly evolutionary conserved function. Recent studies have shown that glia can modulate neuronal activity and behavior. However, how different glia subtypes sense metabolic state and modulate neurons and behavior is incompletely understood. Here, we unravel two types of glia-mediated modulation of metabolic state-dependent behavior. In food-deprived flies, astrocyte-like and perineurial glia promote foraging and feeding, respectively, while cortex glia suppress these behaviors. We further show that adenosine and adenosine receptor modulate intracellular calcium levels in these glia subtypes, which ultimately controls behavior. This study reveals a new mechanism how different glia subtypes sense the metabolic state of the animal and modulate its behavior accordingly.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"117 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926081","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 : 2024-08-08DOI: 10.1101/2024.08.06.606940
Yohannes Teshome, A. Belete, T. Gebre-Mariam
Teff (Eragrostis tef, family Poaceae) is a native cereal crop widely grown in Ethiopia, containing approximately 73% carbohydrates, of which about 30% is resistant starch. This study evaluates resistant starch extracted from teff grain as a film coating material for colon-targeted delivery of metronidazole, used as a model drug. Starch was extracted from teff and resistant starch was isolated from the total starch. Metronidazole core tablets were prepared by wet granulation, compressed, and coated with a resistant starch-based film. The physicochemical properties of the tablets were evaluated in vitro. To prevent premature film disruption caused by the swelling of amylose, a dominant component of resistant starch, a water-insoluble polymer, ethylcellulose, was added. Various proportions of amylose and ethylcellulose were used as film coating materials and evaluated in simulated conditions to determine the optimal combination for drug release in the colon, but not in the upper gastrointestinal tract. The results of the dissolution and fermentation studies indicated the best film coating proportions of amylose to ethylcellulose and the corresponding thicknesses in percentage of total weight gain were: 1:1 ratio at 6% thickness, 1:2 ratio at 4% and 6% thickness, and 1:3 ratio at 2% and 4% thickness. The targeted drug release of the film material is attributed to bacterial enzyme digestion of the resistant starch component in the colon. The digestion of resistant starch creates pores in the ethylcellulose film scaffold, leading to the disruption of the film and release of the drug exclusively in the colon, where the bacterial microflora reside. Based on these results, resistant starch from teff grain shows potential as a colon-targeting excipient.
{"title":"Evaluation of resistant starch from teff (Eragrostis tef) grain as a film coating material for colon-targeted drug delivery","authors":"Yohannes Teshome, A. Belete, T. Gebre-Mariam","doi":"10.1101/2024.08.06.606940","DOIUrl":"https://doi.org/10.1101/2024.08.06.606940","url":null,"abstract":"Teff (Eragrostis tef, family Poaceae) is a native cereal crop widely grown in Ethiopia, containing approximately 73% carbohydrates, of which about 30% is resistant starch. This study evaluates resistant starch extracted from teff grain as a film coating material for colon-targeted delivery of metronidazole, used as a model drug. Starch was extracted from teff and resistant starch was isolated from the total starch. Metronidazole core tablets were prepared by wet granulation, compressed, and coated with a resistant starch-based film. The physicochemical properties of the tablets were evaluated in vitro. To prevent premature film disruption caused by the swelling of amylose, a dominant component of resistant starch, a water-insoluble polymer, ethylcellulose, was added. Various proportions of amylose and ethylcellulose were used as film coating materials and evaluated in simulated conditions to determine the optimal combination for drug release in the colon, but not in the upper gastrointestinal tract. The results of the dissolution and fermentation studies indicated the best film coating proportions of amylose to ethylcellulose and the corresponding thicknesses in percentage of total weight gain were: 1:1 ratio at 6% thickness, 1:2 ratio at 4% and 6% thickness, and 1:3 ratio at 2% and 4% thickness. The targeted drug release of the film material is attributed to bacterial enzyme digestion of the resistant starch component in the colon. The digestion of resistant starch creates pores in the ethylcellulose film scaffold, leading to the disruption of the film and release of the drug exclusively in the colon, where the bacterial microflora reside. Based on these results, resistant starch from teff grain shows potential as a colon-targeting excipient.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"27 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927079","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 : 2024-08-08DOI: 10.1101/2024.08.06.606659
Jessica Lee, Fatma P. Cakmak, Richard Booth, Christine D. Keating
Prebiotically-plausible compartmentalization mechanisms include membrane vesicles formed by amphiphile self-assembly and coacervate droplets formed by liquid-liquid phase separation. Both types of structures form spontaneously and can be related to cellular compartmentalization motifs in today’s living cells. As prebiotic compartments, they have complementary capabilities, with coacervates offering excellent solute accumulation and membranes providing superior boundaries. Herein, we describe protocell models constructed by spontaneous encapsulation of coacervate droplets by mixed fatty acid/phospholipid and by purely fatty acid membranes. Coacervate-supported membranes formed over a range of coacervate and lipid compositions, with membrane properties impacted by charge-charge interactions between coacervates and membranes. Vesicles formed by coacervate-templated membrane assembly exhibited profoundly different permeability than traditional fatty acid or blended fatty acid/phospholipid membranes without coacervate interiors, particularly in the presence of Mg2+ ions. While fatty acid and blended membrane vesicles were disrupted by addition of 25 mM MgCl2, the corresponding coacervate-supported membranes remained intact and impermeable to externally-added solutes even in the presence of MgCl2. With the more robust membrane, fluorescein diacetate (FDA) hydrolysis, which is commonly used for cell viability assays, could be performed inside the protocell model due to the simple diffusion of FDA and then following with the coacervate-mediated abiotic hydrolysis to fluorescein.
生前合理的分隔机制包括通过两性自组装形成的膜囊泡和通过液-液相分离形成的凝聚液滴。这两类结构都是自发形成的，与当今活细胞中的细胞分隔模式有关。作为前生物隔室，它们具有互补性，凝聚态液滴能提供出色的溶质积累，而膜则能提供卓越的边界。在这里，我们描述了由脂肪酸/磷脂混合膜和纯脂肪酸膜自发包裹凝聚态液滴而构建的原细胞模型。在一系列辅水合物和脂质成分中形成了辅水合物支撑膜，辅水合物和膜之间的电荷-电荷相互作用影响了膜的特性。与传统的无凝聚剂内层的脂肪酸膜或脂肪酸/磷脂混合膜相比，由凝聚剂引发的膜组装形成的囊泡表现出截然不同的渗透性，尤其是在 Mg2+ 离子存在的情况下。加入 25 mM MgCl2 会破坏脂肪酸和混合膜囊泡，而相应的有凝聚剂支撑的膜即使在 MgCl2 存在的情况下也能保持完好无损，并且对外部添加的溶质没有渗透性。有了更坚固的膜，由于 FDA 的简单扩散，可在原细胞模型内进行双乙酸荧光素（FDA）水解（常用于细胞存活率检测），然后再通过共凝胶介导的非生物水解生成荧光素。
{"title":"Hybrid Protocells based on Coacervate-Templated Fatty Acid Vesicles combine Improved Membrane Stability with Functional Interior Protocytoplasm","authors":"Jessica Lee, Fatma P. Cakmak, Richard Booth, Christine D. Keating","doi":"10.1101/2024.08.06.606659","DOIUrl":"https://doi.org/10.1101/2024.08.06.606659","url":null,"abstract":"Prebiotically-plausible compartmentalization mechanisms include membrane vesicles formed by amphiphile self-assembly and coacervate droplets formed by liquid-liquid phase separation. Both types of structures form spontaneously and can be related to cellular compartmentalization motifs in today’s living cells. As prebiotic compartments, they have complementary capabilities, with coacervates offering excellent solute accumulation and membranes providing superior boundaries. Herein, we describe protocell models constructed by spontaneous encapsulation of coacervate droplets by mixed fatty acid/phospholipid and by purely fatty acid membranes. Coacervate-supported membranes formed over a range of coacervate and lipid compositions, with membrane properties impacted by charge-charge interactions between coacervates and membranes. Vesicles formed by coacervate-templated membrane assembly exhibited profoundly different permeability than traditional fatty acid or blended fatty acid/phospholipid membranes without coacervate interiors, particularly in the presence of Mg2+ ions. While fatty acid and blended membrane vesicles were disrupted by addition of 25 mM MgCl2, the corresponding coacervate-supported membranes remained intact and impermeable to externally-added solutes even in the presence of MgCl2. With the more robust membrane, fluorescein diacetate (FDA) hydrolysis, which is commonly used for cell viability assays, could be performed inside the protocell model due to the simple diffusion of FDA and then following with the coacervate-mediated abiotic hydrolysis to fluorescein.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"31 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927196","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 : 2024-08-08DOI: 10.1101/2024.08.06.606378
Hao Ye, J. Zang, Jiawei Zhu, D. Arx, Vitaly Pustovalov, Minmin Mao, Qiao Tang, Andrea Veciana, Harun Torlakcik, Elric Zhang, S. Sevim, R. Sanchis-Gual, Xiang-Zhong Chen, Daniel Ahmed, M. V. Sanchez-Vives, Josep Puigmartí‐Luis, Bradley J. Nelson, S. Neuhauss, Salvador Pané
Regenerative medicine continually seeks effective methods to address spinal cord injuries (SCI), which are known for their limited regenerative potential. Despite advances in neural progenitor cell (NPC) transplants for spinal cord injuries, challenges related to graft survival, reliable in vivo differentiation, and neural integration significantly hinder real functional recovery and limit clinical outcomes. This study introduces ‘NPCbots’, biohybrid microrobots engineered by integrating human-induced pluripotent stem cell-derived NPCs with magnetoelectric nanoparticles composed of cobalt ferrite-barium titanate. These enable magnetic navigation and neuronal stimulation, enhancing targeted therapeutic interventions. Our lab-on-a-chip system allows for the mass production of NPCbots, ensuring their differentiation and biocompatibility. Remarkably, in a zebrafish model of SCI, NPCbots stimulated by an alternating magnetic field demonstrated rapid in vivo differentiation and integration into damaged neural pathways, significantly enhancing neural regeneration. Within three days, injured zebrafish treated with NPCbots exhibited almost normal swimming behavior and significantly improved exploratory behavior, showcasing the potential of NPCbots to swiftly repair neural structures and restore the central nervous system’s functionality in spinal cord injury models through non-invasive means. Additionally, precise in vitro and in vivo manipulation of NPCbots indicates their broader application in various neurodegenerative disorders, offering a promising route for effective spinal cord and neurological recovery.
{"title":"Magnetoelectric Microrobots for Spinal Cord Injury Regeneration","authors":"Hao Ye, J. Zang, Jiawei Zhu, D. Arx, Vitaly Pustovalov, Minmin Mao, Qiao Tang, Andrea Veciana, Harun Torlakcik, Elric Zhang, S. Sevim, R. Sanchis-Gual, Xiang-Zhong Chen, Daniel Ahmed, M. V. Sanchez-Vives, Josep Puigmartí‐Luis, Bradley J. Nelson, S. Neuhauss, Salvador Pané","doi":"10.1101/2024.08.06.606378","DOIUrl":"https://doi.org/10.1101/2024.08.06.606378","url":null,"abstract":"Regenerative medicine continually seeks effective methods to address spinal cord injuries (SCI), which are known for their limited regenerative potential. Despite advances in neural progenitor cell (NPC) transplants for spinal cord injuries, challenges related to graft survival, reliable in vivo differentiation, and neural integration significantly hinder real functional recovery and limit clinical outcomes. This study introduces ‘NPCbots’, biohybrid microrobots engineered by integrating human-induced pluripotent stem cell-derived NPCs with magnetoelectric nanoparticles composed of cobalt ferrite-barium titanate. These enable magnetic navigation and neuronal stimulation, enhancing targeted therapeutic interventions. Our lab-on-a-chip system allows for the mass production of NPCbots, ensuring their differentiation and biocompatibility. Remarkably, in a zebrafish model of SCI, NPCbots stimulated by an alternating magnetic field demonstrated rapid in vivo differentiation and integration into damaged neural pathways, significantly enhancing neural regeneration. Within three days, injured zebrafish treated with NPCbots exhibited almost normal swimming behavior and significantly improved exploratory behavior, showcasing the potential of NPCbots to swiftly repair neural structures and restore the central nervous system’s functionality in spinal cord injury models through non-invasive means. Additionally, precise in vitro and in vivo manipulation of NPCbots indicates their broader application in various neurodegenerative disorders, offering a promising route for effective spinal cord and neurological recovery.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"40 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928353","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 : 2024-08-08DOI: 10.1101/2024.08.06.606898
Sophia Snipes
High-frequency brain oscillations in humans are currently categorized into beta (13-30 Hz) and gamma (>30 Hz). Here, I introduce a new class of oscillations between 25 and 35 Hz, which I propose to call “iota.” Iota oscillations have low amplitudes but can still be measured with surface electroencephalography (EEG). Within an individual, iota has a narrow spectral bandwidth of 2-4 Hz, thus distinguishing it from broadband beta and gamma. Iota oscillations occur as sustained bursts during both wakefulness and REM sleep but do not appear during NREM sleep. They are only found in a minority of individuals, more in children than in adults. Overall, iota oscillations are challenging to detect but could serve as a marker of both brain development and states of vigilance.
{"title":"Iota oscillations (25-35 Hz) during wake and REM sleep in children and young adults","authors":"Sophia Snipes","doi":"10.1101/2024.08.06.606898","DOIUrl":"https://doi.org/10.1101/2024.08.06.606898","url":null,"abstract":"High-frequency brain oscillations in humans are currently categorized into beta (13-30 Hz) and gamma (>30 Hz). Here, I introduce a new class of oscillations between 25 and 35 Hz, which I propose to call “iota.” Iota oscillations have low amplitudes but can still be measured with surface electroencephalography (EEG). Within an individual, iota has a narrow spectral bandwidth of 2-4 Hz, thus distinguishing it from broadband beta and gamma. Iota oscillations occur as sustained bursts during both wakefulness and REM sleep but do not appear during NREM sleep. They are only found in a minority of individuals, more in children than in adults. Overall, iota oscillations are challenging to detect but could serve as a marker of both brain development and states of vigilance.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"22 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928722","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 : 2024-08-08DOI: 10.1101/2024.08.03.606469
Emin Serin, Kerstin Ritter, Gunter Schumann, Tobias Banaschewski, A. Marquand, H. Walter
Task-based functional magnetic resonance imaging (tb-fMRI) provides valuable insights into individual differences in the neural basis of cognitive functions because it links specific cognitive tasks to their evoked neural responses. Yet, it is challenging to scale to population-level data due to its cognitive demands, variations in task design across studies, and a limited number of tasks acquired in typical large-scale studies. Here, we present DeepTaskGen, a convolutional neural network (CNN) approach that enables us to generate synthetic task-based contrast maps from resting-state fMRI (rs-fMRI) data. Our method outperforms several benchmarks, exhibiting superior reconstruction performance while retaining inter-individual variation essential for biomarker development. We showcase DeepTaskGen by generating synthetic task images from the UK Biobank cohort, achieving competitive or greater performance compared to actual task contrast maps and resting-state connectomes for predicting a wide range of demographic, cognitive, and clinical variables. This approach will facilitate the study of individual differences and the generation of task-related biomarkers by enabling the generation of arbitrary functional cognitive tasks from readily available rs-fMRI data.
{"title":"Generating Synthetic Task-based Brain Fingerprints for Population Neuroscience Using Deep Learning","authors":"Emin Serin, Kerstin Ritter, Gunter Schumann, Tobias Banaschewski, A. Marquand, H. Walter","doi":"10.1101/2024.08.03.606469","DOIUrl":"https://doi.org/10.1101/2024.08.03.606469","url":null,"abstract":"Task-based functional magnetic resonance imaging (tb-fMRI) provides valuable insights into individual differences in the neural basis of cognitive functions because it links specific cognitive tasks to their evoked neural responses. Yet, it is challenging to scale to population-level data due to its cognitive demands, variations in task design across studies, and a limited number of tasks acquired in typical large-scale studies. Here, we present DeepTaskGen, a convolutional neural network (CNN) approach that enables us to generate synthetic task-based contrast maps from resting-state fMRI (rs-fMRI) data. Our method outperforms several benchmarks, exhibiting superior reconstruction performance while retaining inter-individual variation essential for biomarker development. We showcase DeepTaskGen by generating synthetic task images from the UK Biobank cohort, achieving competitive or greater performance compared to actual task contrast maps and resting-state connectomes for predicting a wide range of demographic, cognitive, and clinical variables. This approach will facilitate the study of individual differences and the generation of task-related biomarkers by enabling the generation of arbitrary functional cognitive tasks from readily available rs-fMRI data.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"35 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927374","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 : 2024-08-08DOI: 10.1101/2024.08.06.606809
Tomasz Slezak, Kelly M. O’Leary, Jinyang Li, A. Rohaim, Elena K. Davydova, A. Kossiakoff
We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner. The simplest manifestation allows multiplexed antigen detection using PG variants fused to fluorescently labeled SNAP-tags. Moreover, Fabs can be readily attached to a PG-Fc dimer module which acts as the core unit to produce plug-and-play IgG-like assemblies, and the utility can be further expanded to produce bispecific analogs using the “knobs into holes” strategy. These core PG-Fc dimer modules can be made and stored in bulk to produce off-the-shelf customized IgG entities in minutes, not days or weeks by just adding a Fab with the desired antigen specificity. In another application, the bispecific modalities form the building block for fabricating potent Bispecific T-cell Engagers (BiTEs), demonstrating their efficacy in cancer cell-killing assays. Additionally, the system can be adapted to include commercial antibodies as building blocks, greatly increasing the target space. Crystal structure analysis reveals that a few strategically positioned interactions engender the specificity between the Fab-PG variant pairs, requiring minimal changes to match the scaffolds for different possible combinations. This plug-and-play platform offers a user-friendly and versatile approach to enhance the functionality of antibody-based reagents in cell biology research.
我们已开发出一系列基于抗体的模块，这些模块可作为独立单元预制，并以即插即用的方式拼接在一起，形成功能独特强大的多功能组件。这些基本构件来自多对原生和修饰的 Fab 支架和蛋白 G (PG) 变体，这些变体通过噬菌体展示工程引入了高配对特异性。各种可能的 Fab-PG 配对提供了一个高度正交的系统，可用于以简单的方式执行具有挑战性的细胞生物学操作。最简单的表现形式是使用融合了荧光标记 SNAP 标签的 PG 变体进行多重抗原检测。此外，Fabs 可以很容易地连接到 PG-Fc 二聚体模块上，而 PG-Fc 二聚体模块是生产即插即用类 IgG 组合物的核心单元，其用途还可以进一步扩展，利用 "钮入孔 "策略生产双特异性类似物。这些核心 PG-Fc 二聚体模块可以批量生产和储存，只需添加具有所需抗原特异性的 Fab，就能在几分钟内而不是几天或几周内生产出现成的定制 IgG 实体。在另一项应用中，双特异性模式构成了制造强效双特异性 T 细胞激活剂（BiTE）的基石，在癌细胞杀伤试验中证明了它们的功效。此外，该系统还可以将商业抗体作为构建模块，从而大大增加了靶标空间。晶体结构分析表明，Fab-PG 变体对之间的特异性是由几个策略性定位的相互作用产生的，只需做极少的改动就能匹配不同可能组合的支架。这种即插即用的平台为增强细胞生物学研究中基于抗体的试剂的功能提供了一种用户友好型多功能方法。
{"title":"Engineered Protein-G variants for plug-and-play applications","authors":"Tomasz Slezak, Kelly M. O’Leary, Jinyang Li, A. Rohaim, Elena K. Davydova, A. Kossiakoff","doi":"10.1101/2024.08.06.606809","DOIUrl":"https://doi.org/10.1101/2024.08.06.606809","url":null,"abstract":"We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner. The simplest manifestation allows multiplexed antigen detection using PG variants fused to fluorescently labeled SNAP-tags. Moreover, Fabs can be readily attached to a PG-Fc dimer module which acts as the core unit to produce plug-and-play IgG-like assemblies, and the utility can be further expanded to produce bispecific analogs using the “knobs into holes” strategy. These core PG-Fc dimer modules can be made and stored in bulk to produce off-the-shelf customized IgG entities in minutes, not days or weeks by just adding a Fab with the desired antigen specificity. In another application, the bispecific modalities form the building block for fabricating potent Bispecific T-cell Engagers (BiTEs), demonstrating their efficacy in cancer cell-killing assays. Additionally, the system can be adapted to include commercial antibodies as building blocks, greatly increasing the target space. Crystal structure analysis reveals that a few strategically positioned interactions engender the specificity between the Fab-PG variant pairs, requiring minimal changes to match the scaffolds for different possible combinations. This plug-and-play platform offers a user-friendly and versatile approach to enhance the functionality of antibody-based reagents in cell biology research.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926320","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：