Pub Date : 2024-11-06DOI: 10.1007/s12064-024-00427-2
Vic Norris
A fundamental problem in biology is how cells obtain the reproducible, coherent phenotypes needed for natural selection to act or, put differently, how cells manage to limit their exploration of the vastness of phenotype space. A subset of this problem is how they regulate their cell cycle. Bacteria, like eukaryotic cells, are highly structured and contain scores of hyperstructures or assemblies of molecules and macromolecules. The existence and functioning of certain of these hyperstructures depend on phase transitions. Here, I propose a conceptual framework to facilitate the development of water-clock hypotheses in which cells use water to generate phenotypes by living 'on the edge of phase transitions'. I give an example of such a hypothesis in the case of the bacterial cell cycle and show how it offers a relatively novel 'view from here' that brings together a range of different findings about hyperstructures, phase transitions and water and that can be integrated with other hypotheses about differentiation, metabolism and the origins of life.
{"title":"Hypothesis: bacteria live on the edge of phase transitions with a cell cycle regulated by a water-clock.","authors":"Vic Norris","doi":"10.1007/s12064-024-00427-2","DOIUrl":"https://doi.org/10.1007/s12064-024-00427-2","url":null,"abstract":"<p><p>A fundamental problem in biology is how cells obtain the reproducible, coherent phenotypes needed for natural selection to act or, put differently, how cells manage to limit their exploration of the vastness of phenotype space. A subset of this problem is how they regulate their cell cycle. Bacteria, like eukaryotic cells, are highly structured and contain scores of hyperstructures or assemblies of molecules and macromolecules. The existence and functioning of certain of these hyperstructures depend on phase transitions. Here, I propose a conceptual framework to facilitate the development of water-clock hypotheses in which cells use water to generate phenotypes by living 'on the edge of phase transitions'. I give an example of such a hypothesis in the case of the bacterial cell cycle and show how it offers a relatively novel 'view from here' that brings together a range of different findings about hyperstructures, phase transitions and water and that can be integrated with other hypotheses about differentiation, metabolism and the origins of life.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1007/s12064-024-00426-3
Nina Kranke
In recent discussions, the widespread conviction that scientific individuation practices are governed by theories and concepts of biological individuality has been challenged, particularly by advocates of practice-based approaches. This discussion raises questions about the relationship between individuation practices and concepts of individuality. In this paper, I discuss four studies of host–parasite systems and analyze the respective individuation practices to see whether they correspond to established concepts of biological individuality. My analysis suggests that scientists individuate biological systems on different levels of organization and that the researchers’ respective emphasis on one of the levels depends on the explanandum and research context as well as epistemic aims and purposes. It thus makes sense to use different concepts of individuality to account for different individuation practices. However, not all individuation practices are represented equally well by concepts of biological individuality. To account for this observation, I propose that concepts of individuality should be understood as abstracted, idealized, or simplified models that represent only certain aspects of scientific practice. A modeling account suggests a pluralistic view of concepts of biological individuality that not only allows the coexistence of different kinds of individuality (e.g., evolutionary individuality, immunological individuality, ecological individuality) but also of normative and descriptive concepts.
{"title":"Do concepts of individuality account for individuation practices in studies of host–parasite systems? A modeling account of biological individuality","authors":"Nina Kranke","doi":"10.1007/s12064-024-00426-3","DOIUrl":"https://doi.org/10.1007/s12064-024-00426-3","url":null,"abstract":"<p>In recent discussions, the widespread conviction that scientific individuation practices are governed by theories and concepts of biological individuality has been challenged, particularly by advocates of practice-based approaches. This discussion raises questions about the relationship between individuation practices and concepts of individuality. In this paper, I discuss four studies of host–parasite systems and analyze the respective individuation practices to see whether they correspond to established concepts of biological individuality. My analysis suggests that scientists individuate biological systems on different levels of organization and that the researchers’ respective emphasis on one of the levels depends on the explanandum and research context as well as epistemic aims and purposes. It thus makes sense to use different concepts of individuality to account for different individuation practices. However, not all individuation practices are represented equally well by concepts of biological individuality. To account for this observation, I propose that concepts of individuality should be understood as abstracted, idealized, or simplified models that represent only certain aspects of scientific practice. A modeling account suggests a pluralistic view of concepts of biological individuality that not only allows the coexistence of different kinds of individuality (e.g., evolutionary individuality, immunological individuality, ecological individuality) but also of normative and descriptive concepts.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1007/s12064-024-00425-4
Guillermo Restrepo
In an effort to expand the domain of mathematical chemistry and inspire research beyond the realms of graph theory and quantum chemistry, we explore five mathematical chemistry spaces and their interconnectedness. These spaces comprise the chemical space, which encompasses substances and reactions; the space of reaction conditions, spanning the physical and chemical aspects involved in chemical reactions; the space of reaction grammars, which encapsulates the rules for creating and breaking chemical bonds; the space of substance properties, covering all documented measurements regarding substances; and the space of substance representations, composed of the various ontologies for characterising substances.
{"title":"Spaces of mathematical chemistry","authors":"Guillermo Restrepo","doi":"10.1007/s12064-024-00425-4","DOIUrl":"https://doi.org/10.1007/s12064-024-00425-4","url":null,"abstract":"<p>In an effort to expand the domain of mathematical chemistry and inspire research beyond the realms of graph theory and quantum chemistry, we explore five mathematical chemistry spaces and their interconnectedness. These spaces comprise the chemical space, which encompasses substances and reactions; the space of reaction conditions, spanning the physical and chemical aspects involved in chemical reactions; the space of reaction grammars, which encapsulates the rules for creating and breaking chemical bonds; the space of substance properties, covering all documented measurements regarding substances; and the space of substance representations, composed of the various ontologies for characterising substances.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-19DOI: 10.1007/s12064-024-00422-7
Ulrich Zeller, Ingmar Werneburg
Until the mid-nineteenth century, "physiology" was a comprehensive theory of life, expounded and shaped by Johannes P. Müller (1801-1858). Biologists and medical doctors still refer to him today. In the summer term of 1851, Müller gave a lecture on the Comparative Anatomy of animals. This lecture was attended and recorded by Ernst Zeller (1830-1902), a future physician and zoologist, and has recently been published together with a German transcript. In this paper, we situate Johannes Müller within the intellectual history of his time. Through his "empirical idealism," we show how he opposed the speculative tendencies of the romantic understanding of nature, the emerging evolutionism, and the growing splits in the natural sciences. Müller focused on recognizing living nature as a whole and realizing ideal "phenomena" through his empirical research. He considered the notion of the soul of the world. Müller's lecture transcript serves as a poignant testament to German scientific culture in the mid-nineteenth century, a few years before the publication of Darwin's Origin of Species. It also provides valuable insights into the self-contained epistemological foundations of morphology.
直到十九世纪中叶,"生理学 "一直是由约翰内斯-P-穆勒(Johannes P. Müller,1801-1858 年)阐述和形成的关于生命的综合理论。今天,生物学家和医生们仍会提到他。1851 年夏季学期,缪勒发表了关于动物比较解剖学的演讲。恩斯特-泽勒(Ernst Zeller,1830-1902 年)--一位未来的医生和动物学家--参加了这次讲座并作了记录,最近他的讲座连同德文记录稿一起出版。在本文中,我们将约翰内斯-缪勒置于他所处时代的思想史中。通过他的 "经验唯心主义",我们展示了他是如何反对浪漫主义自然理解的投机倾向、新兴的进化论以及自然科学中日益增长的分裂。穆勒专注于将有生命的自然界视为一个整体,并通过他的经验研究实现理想的 "现象"。他思考了世界灵魂的概念。缪勒的演讲记录是十九世纪中叶德国科学文化的重要见证,当时距离达尔文的《物种起源》出版还有几年时间。它还为我们了解形态学自成一体的认识论基础提供了宝贵的见解。
{"title":"A life dedicated to research and ideal: Johannes Müller between empirical universality and idealistic vitalism mirrored in lecture notes from 1851.","authors":"Ulrich Zeller, Ingmar Werneburg","doi":"10.1007/s12064-024-00422-7","DOIUrl":"10.1007/s12064-024-00422-7","url":null,"abstract":"<p><p>Until the mid-nineteenth century, \"physiology\" was a comprehensive theory of life, expounded and shaped by Johannes P. Müller (1801-1858). Biologists and medical doctors still refer to him today. In the summer term of 1851, Müller gave a lecture on the Comparative Anatomy of animals. This lecture was attended and recorded by Ernst Zeller (1830-1902), a future physician and zoologist, and has recently been published together with a German transcript. In this paper, we situate Johannes Müller within the intellectual history of his time. Through his \"empirical idealism,\" we show how he opposed the speculative tendencies of the romantic understanding of nature, the emerging evolutionism, and the growing splits in the natural sciences. Müller focused on recognizing living nature as a whole and realizing ideal \"phenomena\" through his empirical research. He considered the notion of the soul of the world. Müller's lecture transcript serves as a poignant testament to German scientific culture in the mid-nineteenth century, a few years before the publication of Darwin's Origin of Species. It also provides valuable insights into the self-contained epistemological foundations of morphology.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-18DOI: 10.1007/s12064-024-00419-2
Xianchun Duan, Ni Wang, Daiyin Peng
Herbal medicines are frequently blended in the form of multi-drug combinations primarily based on the precept of medicinal compatibility, to achieve the purpose of treating diseases. However, due to the lack of appropriate techniques and the multi-component and multi-target nature of Chinese medicine compounding, it is tough to explain how the drugs interact with each other. As a rising discipline, cyber pharmacology has formed a new approach characterized by using holistic and systematic "network targets" via the cross-fertilization of computer technology, bioinformatics, and different multidisciplinary disciplines. It can broadly screen the active ingredients of traditional Chinese medicine, enhance the effective utilization of drugs, and elucidate the mechanism of drug action. We will overview the principles of Chinese medicine compounding and dispensing, the research methods of network pharmacology, and the software of network pharmacology in the lookup of compounded Chinese medicines, aiming to supply thoughts for the better application of network pharmacology in the research of Chinese medicines.
{"title":"Application of network pharmacology in synergistic action of Chinese herbal compounds.","authors":"Xianchun Duan, Ni Wang, Daiyin Peng","doi":"10.1007/s12064-024-00419-2","DOIUrl":"10.1007/s12064-024-00419-2","url":null,"abstract":"<p><p>Herbal medicines are frequently blended in the form of multi-drug combinations primarily based on the precept of medicinal compatibility, to achieve the purpose of treating diseases. However, due to the lack of appropriate techniques and the multi-component and multi-target nature of Chinese medicine compounding, it is tough to explain how the drugs interact with each other. As a rising discipline, cyber pharmacology has formed a new approach characterized by using holistic and systematic \"network targets\" via the cross-fertilization of computer technology, bioinformatics, and different multidisciplinary disciplines. It can broadly screen the active ingredients of traditional Chinese medicine, enhance the effective utilization of drugs, and elucidate the mechanism of drug action. We will overview the principles of Chinese medicine compounding and dispensing, the research methods of network pharmacology, and the software of network pharmacology in the lookup of compounded Chinese medicines, aiming to supply thoughts for the better application of network pharmacology in the research of Chinese medicines.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-26DOI: 10.1007/s12064-024-00420-9
Diogo Gonçalves
The definition, origin and recreation of life remain elusive. As others have suggested, only once we put life into reductionist physical terms will we be able to solve those questions. To that end, this work proposes the phenomenon of life to be the product of two dissipative mechanisms. From them, one characterises extant biological life and deduces a testable scenario for its origin. The proposed theory of life allows its replication, reinterprets ecological evolution and creates new constraints on the search for life.
{"title":"Rethinking life and predicting its origin.","authors":"Diogo Gonçalves","doi":"10.1007/s12064-024-00420-9","DOIUrl":"10.1007/s12064-024-00420-9","url":null,"abstract":"<p><p>The definition, origin and recreation of life remain elusive. As others have suggested, only once we put life into reductionist physical terms will we be able to solve those questions. To that end, this work proposes the phenomenon of life to be the product of two dissipative mechanisms. From them, one characterises extant biological life and deduces a testable scenario for its origin. The proposed theory of life allows its replication, reinterprets ecological evolution and creates new constraints on the search for life.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-28DOI: 10.1007/s12064-024-00418-3
T Mallikarjuna, N B Thummadi, Vaibhav Vindal, P Manimaran
Cervical cancer is one of the most severe threats to women worldwide and holds fourth rank in lethality. It is estimated that 604, 127 cervical cancer cases have been reported in 2020 globally. With advancements in high throughput technologies and bioinformatics, several cervical candidate genes have been proposed for better therapeutic strategies. In this paper, we intend to prioritize the candidate genes that are involved in cervical cancer progression through a fractal time series-based cross-correlations approach. we apply the chaos game representation theory combining a two-dimensional multifractal detrended cross-correlations approach among the known and candidate genes involved in cervical cancer progression to prioritize the candidate genes. We obtained 16 candidate genes that showed cross-correlation with known cancer genes. Functional enrichment analysis of the candidate genes shows that they involve GO terms: biological processes, cell-cell junction assembly, cell-cell junction organization, regulation of cell shape, cortical actin cytoskeleton organization, and actomyosin structure organization. KEGG pathway analysis revealed genes' role in Rap1 signaling pathway, ErbB signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, Acute myeloid leukemia, chronic myeloid leukemia, Breast cancer, Thyroid cancer, Bladder cancer, and Gastric cancer. Further, we performed survival analysis and prioritized six genes CDH2, PAIP1, BRAF, EPB41L3, OSMR, and RUNX1 as potential candidate genes for cervical cancer that has a crucial role in tumor progression. We found that our study through this integrative approach an efficient tool and paved a new way to prioritize the candidate genes and these genes could be evaluated experimentally for potential validation. We suggest this may be useful in analyzing the nucleotide sequences and protein sequences for clustering, classification, class affiliation, etc.
{"title":"Prioritizing cervical cancer candidate genes using chaos game and fractal-based time series approach.","authors":"T Mallikarjuna, N B Thummadi, Vaibhav Vindal, P Manimaran","doi":"10.1007/s12064-024-00418-3","DOIUrl":"10.1007/s12064-024-00418-3","url":null,"abstract":"<p><p>Cervical cancer is one of the most severe threats to women worldwide and holds fourth rank in lethality. It is estimated that 604, 127 cervical cancer cases have been reported in 2020 globally. With advancements in high throughput technologies and bioinformatics, several cervical candidate genes have been proposed for better therapeutic strategies. In this paper, we intend to prioritize the candidate genes that are involved in cervical cancer progression through a fractal time series-based cross-correlations approach. we apply the chaos game representation theory combining a two-dimensional multifractal detrended cross-correlations approach among the known and candidate genes involved in cervical cancer progression to prioritize the candidate genes. We obtained 16 candidate genes that showed cross-correlation with known cancer genes. Functional enrichment analysis of the candidate genes shows that they involve GO terms: biological processes, cell-cell junction assembly, cell-cell junction organization, regulation of cell shape, cortical actin cytoskeleton organization, and actomyosin structure organization. KEGG pathway analysis revealed genes' role in Rap1 signaling pathway, ErbB signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, Acute myeloid leukemia, chronic myeloid leukemia, Breast cancer, Thyroid cancer, Bladder cancer, and Gastric cancer. Further, we performed survival analysis and prioritized six genes CDH2, PAIP1, BRAF, EPB41L3, OSMR, and RUNX1 as potential candidate genes for cervical cancer that has a crucial role in tumor progression. We found that our study through this integrative approach an efficient tool and paved a new way to prioritize the candidate genes and these genes could be evaluated experimentally for potential validation. We suggest this may be useful in analyzing the nucleotide sequences and protein sequences for clustering, classification, class affiliation, etc.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-30DOI: 10.1007/s12064-024-00421-8
Sunil Nath
The F1-ATPase enzyme is the smallest-known molecular motor that rotates in 120° steps, driven by the hydrolysis of ATP. It is a multi-subunit enzyme that contains three catalytic sites. A central question is how the elementary chemical reactions that occur in the three sites are coupled to mechanical rotation. Various models and coupling schemes have been formulated in an attempt to answer this question. They can be classified as 2-site (bi-site) models, exemplified by Boyer's binding change mechanism first proposed 50 years ago, and 3-site (tri-site) models such as Nath's torsional mechanism, first postulated 25 years ago and embellished 1 year back. Experimental data collated using diverse approaches have conclusively shown that steady-state ATP hydrolysis by F1-ATPase occurs in tri-site mode. Hence older models have been continually modified to make them conform to the new facts. Here, we have developed a pure mathematical approach based on combinatorics and conservation laws to test if proposed models are 2-site or 3-site. Based on this novel combinatorial approach, we have proved that older and modified models are effectively bi‒site models in that catalysis and rotation in F1-ATPase occurs in these models with only two catalytic sites occupied by bound nucleotide. Hence these models contradict consensus experimental data. The recent 2023 model of ATP hydrolysis by F1-ATPase has been proved to be a true tri-site model based on our novel mathematical approach. Such pure mathematical proofs constitute an important step forward for ATP mechanism. However, in what must be considered an aspect with great scientific potential, the power of such mathematical proofs has not been fully exploited to solve molecular biological problems, in our opinion. We believe that the creative application of pure mathematical proofs (for another example see Nath in Theory Biosci 141:249-260, 2022) can help resolve with finality various longstanding molecular-level issues that arise as a matter of course in the analysis of fundamental biological problems. Such issues have proved extraordinarily difficult to resolve by standard experimental, theoretical, or computational approaches.
F1-ATPase 酶是已知的最小分子马达,在 ATP 的水解作用驱动下以 120° 的步长旋转。它是一种多亚基酶,包含三个催化位点。一个核心问题是,这三个位点发生的基本化学反应如何与机械旋转耦合。为了回答这个问题,人们提出了各种模型和耦合方案。它们可分为两个位点(双位点)模型和三个位点(三位点)模型,前者如 Boyer 于 50 年前首次提出的结合变化机制,后者如 Nath 于 25 年前首次提出并在 1 年前完善的扭转机制。使用不同方法整理的实验数据已确凿表明,F1-ATP 酶的稳态 ATP 水解发生在三位模式中。因此,人们不断修改旧模型,使其符合新的事实。在此,我们开发了一种基于组合学和守恒定律的纯数学方法,以检验所提出的模型是 2 位还是 3 位。基于这种新颖的组合方法,我们证明了旧模型和修改后的模型实际上是双位点模型,因为在这些模型中,F1-ATPase 的催化和旋转只发生在两个被结合核苷酸占据的催化位点上。因此,这些模型与一致的实验数据相矛盾。根据我们新颖的数学方法,最近关于 F1-ATP 酶水解 ATP 的 2023 模型已被证明是一个真正的三位点模型。这种纯数学证明是 ATP 机理的重要一步。然而,在我们看来,这种纯数学证明在解决分子生物学问题方面还没有充分发挥其巨大的科学潜力。我们相信,创造性地应用纯数学证明(另一个例子见 Nath 在 Theory Biosci 141:249-260, 2022 中的文章)有助于最终解决在分析基本生物问题时理所当然会出现的各种长期存在的分子级问题。事实证明,标准的实验、理论或计算方法很难解决这些问题。
{"title":"2-Site versus 3-site models of ATP hydrolysis by F<sub>1</sub>-ATPase: definitive mathematical proof using combinatorics and conservation equations.","authors":"Sunil Nath","doi":"10.1007/s12064-024-00421-8","DOIUrl":"10.1007/s12064-024-00421-8","url":null,"abstract":"<p><p>The F<sub>1</sub>-ATPase enzyme is the smallest-known molecular motor that rotates in 120° steps, driven by the hydrolysis of ATP. It is a multi-subunit enzyme that contains three catalytic sites. A central question is how the elementary chemical reactions that occur in the three sites are coupled to mechanical rotation. Various models and coupling schemes have been formulated in an attempt to answer this question. They can be classified as 2-site (bi-site) models, exemplified by Boyer's binding change mechanism first proposed 50 years ago, and 3-site (tri-site) models such as Nath's torsional mechanism, first postulated 25 years ago and embellished 1 year back. Experimental data collated using diverse approaches have conclusively shown that steady-state ATP hydrolysis by F<sub>1</sub>-ATPase occurs in tri-site mode. Hence older models have been continually modified to make them conform to the new facts. Here, we have developed a pure mathematical approach based on combinatorics and conservation laws to test if proposed models are 2-site or 3-site. Based on this novel combinatorial approach, we have proved that older and modified models are effectively bi‒site models in that catalysis and rotation in F<sub>1</sub>-ATPase occurs in these models with only two catalytic sites occupied by bound nucleotide. Hence these models contradict consensus experimental data. The recent 2023 model of ATP hydrolysis by F<sub>1</sub>-ATPase has been proved to be a true tri-site model based on our novel mathematical approach. Such pure mathematical proofs constitute an important step forward for ATP mechanism. However, in what must be considered an aspect with great scientific potential, the power of such mathematical proofs has not been fully exploited to solve molecular biological problems, in our opinion. We believe that the creative application of pure mathematical proofs (for another example see Nath in Theory Biosci 141:249-260, 2022) can help resolve with finality various longstanding molecular-level issues that arise as a matter of course in the analysis of fundamental biological problems. Such issues have proved extraordinarily difficult to resolve by standard experimental, theoretical, or computational approaches.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-03DOI: 10.1007/s12064-024-00423-6
Michael Bordonaro
The phenomenon of near death and dying experiences has been both of popular interest and of scientific speculation. However, the reality of mental perception at the point of death is currently a subjective experience and has not been formally evaluated. While postmortem gene expression, even in humans, has been evaluated, restoration of postmortem brain activity has heretofore only been attempted in animal models, at the molecular and cellular levels. Meanwhile, progress has been made to translate brain activity of living humans into speech and images. This paper proposes two inter-related thought experiments. First, assuming progress and refinement of the technology of translating human brain activity into interpretable speech and images, can an objective analysis of death experiences be obtained by utilizing these technologies on dying humans? Second, can human brain function be revived postmortem and, if so, can the relevant technologies be utilized for communication with (recently) deceased individuals? In this paper, these questions are considered and possible implications explored.
{"title":"Postmortem communication.","authors":"Michael Bordonaro","doi":"10.1007/s12064-024-00423-6","DOIUrl":"10.1007/s12064-024-00423-6","url":null,"abstract":"<p><p>The phenomenon of near death and dying experiences has been both of popular interest and of scientific speculation. However, the reality of mental perception at the point of death is currently a subjective experience and has not been formally evaluated. While postmortem gene expression, even in humans, has been evaluated, restoration of postmortem brain activity has heretofore only been attempted in animal models, at the molecular and cellular levels. Meanwhile, progress has been made to translate brain activity of living humans into speech and images. This paper proposes two inter-related thought experiments. First, assuming progress and refinement of the technology of translating human brain activity into interpretable speech and images, can an objective analysis of death experiences be obtained by utilizing these technologies on dying humans? Second, can human brain function be revived postmortem and, if so, can the relevant technologies be utilized for communication with (recently) deceased individuals? In this paper, these questions are considered and possible implications explored.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.1007/s12064-024-00424-5
Anuraag Bukkuri
Understanding the ecological and evolutionary dynamics of populations is critical for both basic and applied purposes in a variety of biological contexts. Although several modeling frameworks have been developed to simulate eco-evolutionary dynamics, many fewer address how to model structured populations. In a prior paper, we put forth the first modeling approach to simulate eco-evolutionary dynamics in structured populations under the G function modeling framework. However, this approach does not allow for accurate simulation under fluctuating environmental conditions. To address this limitation, we draw on the study of periodic differential equations to propose a modified approach that uses a different definition of fitness more suitable for fluctuating environments. We illustrate this method with a simple toy model of life history trade-offs. The generality of this approach allows it to be used in a variety of biological contexts.
了解种群的生态和进化动态对于各种生物领域的基础和应用都至关重要。尽管目前已经开发了多个模拟生态进化动态的建模框架,但涉及如何模拟结构化种群的建模框架却少之又少。在之前的一篇论文中,我们首次提出了在 G 函数建模框架下模拟结构种群生态进化动态的建模方法。然而,这种方法无法在波动的环境条件下进行精确模拟。为了解决这一局限性,我们借鉴了周期微分方程的研究,提出了一种改进的方法,即使用更适合波动环境的不同适存度定义。我们用一个简单的生命史权衡玩具模型来说明这种方法。这种方法的通用性使其可用于各种生物环境。
{"title":"Eco-evolutionary dynamics of structured populations in periodically fluctuating environments: a G function approach.","authors":"Anuraag Bukkuri","doi":"10.1007/s12064-024-00424-5","DOIUrl":"https://doi.org/10.1007/s12064-024-00424-5","url":null,"abstract":"<p><p>Understanding the ecological and evolutionary dynamics of populations is critical for both basic and applied purposes in a variety of biological contexts. Although several modeling frameworks have been developed to simulate eco-evolutionary dynamics, many fewer address how to model structured populations. In a prior paper, we put forth the first modeling approach to simulate eco-evolutionary dynamics in structured populations under the G function modeling framework. However, this approach does not allow for accurate simulation under fluctuating environmental conditions. To address this limitation, we draw on the study of periodic differential equations to propose a modified approach that uses a different definition of fitness more suitable for fluctuating environments. We illustrate this method with a simple toy model of life history trade-offs. The generality of this approach allows it to be used in a variety of biological contexts.</p>","PeriodicalId":54428,"journal":{"name":"Theory in Biosciences","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}