Pub Date : 2024-08-08DOI: 10.1101/2024.08.08.607154
Miquel Rosas-Salvans, Caleb J. Rux, Moumita Das, Sophie Dumont
The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. We recently uncovered that the kinetochore complex Astrin-SKAP, which binds microtubules, reduces rather than increases friction at the mammalian kinetochore-microtubule interface. How it does so is not known. Astrin-SKAP could affect how other kinetochore complexes bind microtubules, reducing their friction along microtubules, or it could itself bind microtubules with similar affinity but lower friction than other attachment factors. Using SKAP mutants unable to bind microtubules, live imaging and laser ablation, we show that SKAP’s microtubule binding is essential for sister kinetochore coordination, force dissipation at the interface and attachment responsiveness to force changes. Further, we show that SKAP’s microtubule binding is essential to prevent chromosome detachment under both spindle forces and microneedle-generated forces. Together, our findings indicate that SKAP’s microtubule binding reduces kinetochore friction and increases attachment responsiveness and stability under force. We propose that having complexes with both high and low sliding friction on microtubules, making a mechanically heterogeneous interface, is key to maintaining robust attachments under force and thus accurate segregation.
{"title":"SKAP binding to microtubules reduces friction at the kinetochore-microtubule interface and increases attachment stability under force","authors":"Miquel Rosas-Salvans, Caleb J. Rux, Moumita Das, Sophie Dumont","doi":"10.1101/2024.08.08.607154","DOIUrl":"https://doi.org/10.1101/2024.08.08.607154","url":null,"abstract":"The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. We recently uncovered that the kinetochore complex Astrin-SKAP, which binds microtubules, reduces rather than increases friction at the mammalian kinetochore-microtubule interface. How it does so is not known. Astrin-SKAP could affect how other kinetochore complexes bind microtubules, reducing their friction along microtubules, or it could itself bind microtubules with similar affinity but lower friction than other attachment factors. Using SKAP mutants unable to bind microtubules, live imaging and laser ablation, we show that SKAP’s microtubule binding is essential for sister kinetochore coordination, force dissipation at the interface and attachment responsiveness to force changes. Further, we show that SKAP’s microtubule binding is essential to prevent chromosome detachment under both spindle forces and microneedle-generated forces. Together, our findings indicate that SKAP’s microtubule binding reduces kinetochore friction and increases attachment responsiveness and stability under force. We propose that having complexes with both high and low sliding friction on microtubules, making a mechanically heterogeneous interface, is key to maintaining robust attachments under force and thus accurate segregation.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927957","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: 10.1101/2024.08.08.607247
Romanthi J. Madawala, Jasmine L. Banks, Sarah E. Hancock, L. Quek, Nigel Turner, Lindsay E. Wu
Nicotinamide mononucleotide (NMN) is a widely investigated metabolic precursor to the prominent redox cofactor nicotinamide adenine dinucleotide (NAD+), where it is assumed that delivery of this compound results in its direct incorporation into NAD+ via the canonical salvage / recycling pathway. Surprisingly, treatment with this salvage pathway intermediate leads to increases in nicotinic acid mononucleotide (NaMN) and nicotinic acid adenine dinucleotide (NaAD), two members of the Preiss-Handler / de novo pathways. In mammals, these pathways are not known to intersect prior to the production of NAD+. Here, we show that the cell surface enzyme CD38 can mediate a base exchange reaction on NMN, whereby the nicotinamide ring is exchanged with a free nicotinic acid to yield the Preiss-Handler / de novo pathway intermediate NaMN, with in vivo small molecule inhibition of CD38 abolishing the NMN-induced increase in NaMN and NaAD. Together, these data demonstrate a new mechanism by which the salvage pathway and Preiss-Handler / de novo pathways can exchange intermediates in mammalian NAD+ biosynthesis.
{"title":"CD38 mediates nicotinamide mononucleotide (NMN) base exchange to yield nicotinic acid mononucleotide (NaMN)","authors":"Romanthi J. Madawala, Jasmine L. Banks, Sarah E. Hancock, L. Quek, Nigel Turner, Lindsay E. Wu","doi":"10.1101/2024.08.08.607247","DOIUrl":"https://doi.org/10.1101/2024.08.08.607247","url":null,"abstract":"Nicotinamide mononucleotide (NMN) is a widely investigated metabolic precursor to the prominent redox cofactor nicotinamide adenine dinucleotide (NAD+), where it is assumed that delivery of this compound results in its direct incorporation into NAD+ via the canonical salvage / recycling pathway. Surprisingly, treatment with this salvage pathway intermediate leads to increases in nicotinic acid mononucleotide (NaMN) and nicotinic acid adenine dinucleotide (NaAD), two members of the Preiss-Handler / de novo pathways. In mammals, these pathways are not known to intersect prior to the production of NAD+. Here, we show that the cell surface enzyme CD38 can mediate a base exchange reaction on NMN, whereby the nicotinamide ring is exchanged with a free nicotinic acid to yield the Preiss-Handler / de novo pathway intermediate NaMN, with in vivo small molecule inhibition of CD38 abolishing the NMN-induced increase in NaMN and NaAD. Together, these data demonstrate a new mechanism by which the salvage pathway and Preiss-Handler / de novo pathways can exchange intermediates in mammalian NAD+ biosynthesis.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928814","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: 10.1101/2024.08.06.606816
Marie Steinacker, Y. Kheifetz, Markus Scholz
Background Thrombocytopenia is a common side effect of cytotoxic chemotherapies, which is often dose-limiting. Predicting an individual’s risk is of high clinical importance, as otherwise, a small subgroup of patients limits dosages for the overall population for safety reasons. Methods We aim to predict individual platelet dynamics using non-linear auto-regressive networks with exogenous inputs (NARX). We consider different architectures of the NARX networks, namely feed-forward networks (FNN) and gated recurrent units (GRU). To cope with the relative sparsity of individual patient data, we employ transfer learning (TL) approaches based on a semi-mechanistic model of hematotoxicity. We use a large data set of patients with high-grade non-Hodgkin’s lymphoma to learn the respective models on an individual scale and to compare prediction performances with that of the semi-mechanistic model. Results Of the examined network models, the NARX with GRU architecture performs best. In comparison to the semi-mechanistic model, the network model can result in a substantial improvement of prediction accuracy for patients with irregular dynamics, given well-spaced measurements. TL improves individual prediction performances. Conclusion NARX networks can be utilized to predict an individual’s thrombotoxic response to cytotoxic chemotherapy treatment. For reasonable model learning, we recommend at least three well-spaced measurements per cycle: at baseline, during the nadir phase and during the recovery phase. We aim at generalizing our approach to other treatment scenarios and blood lineages in the future.
{"title":"Predicting chemotherapy-induced thrombotoxicity by NARX neural networks and transfer learning","authors":"Marie Steinacker, Y. Kheifetz, Markus Scholz","doi":"10.1101/2024.08.06.606816","DOIUrl":"https://doi.org/10.1101/2024.08.06.606816","url":null,"abstract":"Background Thrombocytopenia is a common side effect of cytotoxic chemotherapies, which is often dose-limiting. Predicting an individual’s risk is of high clinical importance, as otherwise, a small subgroup of patients limits dosages for the overall population for safety reasons. Methods We aim to predict individual platelet dynamics using non-linear auto-regressive networks with exogenous inputs (NARX). We consider different architectures of the NARX networks, namely feed-forward networks (FNN) and gated recurrent units (GRU). To cope with the relative sparsity of individual patient data, we employ transfer learning (TL) approaches based on a semi-mechanistic model of hematotoxicity. We use a large data set of patients with high-grade non-Hodgkin’s lymphoma to learn the respective models on an individual scale and to compare prediction performances with that of the semi-mechanistic model. Results Of the examined network models, the NARX with GRU architecture performs best. In comparison to the semi-mechanistic model, the network model can result in a substantial improvement of prediction accuracy for patients with irregular dynamics, given well-spaced measurements. TL improves individual prediction performances. Conclusion NARX networks can be utilized to predict an individual’s thrombotoxic response to cytotoxic chemotherapy treatment. For reasonable model learning, we recommend at least three well-spaced measurements per cycle: at baseline, during the nadir phase and during the recovery phase. We aim at generalizing our approach to other treatment scenarios and blood lineages in the future.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141928967","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: 10.1101/2024.08.06.606866
Ganlin Qu, H. A. L. Ribeiro, Angelica L Solomon, L. Vieira, Yana Goddard, N. Diodati, Arantxa V Lazarte, Matthew Wheeler, Reinhard Laubenbacher, B. Mehrad
Invasive aspergillosis is characterized by lung hemorrhage and release of extracellular heme, which promotes fungal growth. Heme can also mediate tissue injury directly, and both fungal growth and lung injury may induce hemorrhage. To assimilate these interdependent processes, we hypothesized that, during aspergillosis, heme mediates direct lung injury independent of fungal growth, leading to worse infection outcomes, and the scavenger protein, hemopexin, mitigates these effects. Mice with neutropenic aspergillosis were found to have a time-dependent increase in lung extracellular heme and a corresponding hemopexin induction. Hemopexin deficiency resulted in markedly increased lung injury, fungal growth, and lung hemorrhage. Using a computational model of the interactions of Aspergillus, heme, and the host, we predicted a critical role for heme-mediated generation of neutrophil-extracellular traps in this infection. We tested this prediction using a fungal strain unable to grow at body temperature, and found that extracellular heme and fungal exposure synergize to induce lung injury by promoting NET release, and disruption of NETs was sufficient to attenuate lung injury and fungal burden. These data implicate heme-mediated NETosis in both lung injury and fungal growth during aspergillosis, resulting in a detrimental positive feedback cycle that can be interrupted by scavenging heme or disrupting NETs.
{"title":"The heme-scavenger, hemopexin, protects against fungal lung injury by mitigating NETosis: an experimental and computational study","authors":"Ganlin Qu, H. A. L. Ribeiro, Angelica L Solomon, L. Vieira, Yana Goddard, N. Diodati, Arantxa V Lazarte, Matthew Wheeler, Reinhard Laubenbacher, B. Mehrad","doi":"10.1101/2024.08.06.606866","DOIUrl":"https://doi.org/10.1101/2024.08.06.606866","url":null,"abstract":"Invasive aspergillosis is characterized by lung hemorrhage and release of extracellular heme, which promotes fungal growth. Heme can also mediate tissue injury directly, and both fungal growth and lung injury may induce hemorrhage. To assimilate these interdependent processes, we hypothesized that, during aspergillosis, heme mediates direct lung injury independent of fungal growth, leading to worse infection outcomes, and the scavenger protein, hemopexin, mitigates these effects. Mice with neutropenic aspergillosis were found to have a time-dependent increase in lung extracellular heme and a corresponding hemopexin induction. Hemopexin deficiency resulted in markedly increased lung injury, fungal growth, and lung hemorrhage. Using a computational model of the interactions of Aspergillus, heme, and the host, we predicted a critical role for heme-mediated generation of neutrophil-extracellular traps in this infection. We tested this prediction using a fungal strain unable to grow at body temperature, and found that extracellular heme and fungal exposure synergize to induce lung injury by promoting NET release, and disruption of NETs was sufficient to attenuate lung injury and fungal burden. These data implicate heme-mediated NETosis in both lung injury and fungal growth during aspergillosis, resulting in a detrimental positive feedback cycle that can be interrupted by scavenging heme or disrupting NETs.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926878","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":null,"pages":null},"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":null,"pages":null},"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: 10.1101/2024.08.06.606757
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":null,"pages":null},"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}
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":null,"pages":null},"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}
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":null,"pages":null},"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: 10.1101/2024.08.06.606378
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":null,"pages":null},"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}
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