During listerial invasion of host cells, these membrane defects can disrupt phagosome membranes, allowing bacteria to escape into the cytosol and rapidly multiply. The activity of listeriolysin O is profoundly dependent on the amount and accessibility of cholesterol in the lipid membrane, which can be modulated by the phospholipase PlcB. All these prominent features of listeriolysin O play a role during different stages of the L. monocytogenes life cycle by promoting the proliferation of the pathogen while mitigating excessive damage to its replicative niche in the cytosol of the host cell.In a series of lectures given in 2003, soon after receiving the Fields Medal for his results in the Algebraic Geometry, Vladimir Voevodsky (1966-2017) identifies two strategic goals for mathematics, which he plans to pursue in his further research. https://www.selleckchem.com/products/stf-083010.html The first goal is to develop a ''computerised library of mathematical knowledge,'' which supports an automated proof-verification. The second goal is to ''bridge pure and applied mathematics.'' Voevodsky's research towards the first goal brought about the new Univalent foundations of mathematics. In view of the second goal Voevodsky in 2004 started to develop a mathematical theory of Population Dynamics, which involved the Categorical Probability theory. This latter project did not bring published results and was abandoned by Voevodsky in 2009 when he decided to focus his efforts on the Univalent foundations and closely related topics. In the present paper, which is based on Voevodsky's archival sources, I present Voevodsky's views of mathematics and its relationships with natural sciences, critically discuss these views, and suggest how Voevodsky's ideas and approaches in the applied mathematics can be further developed and pursued. A special attention is given to Voevodsky's original strategy to bridge the persisting gap between pure and applied mathematics where computers and the computer-assisted mathematics play a major role.The positivistic views that dominated the early debate on the foundations of mathematics, at the beginning of the 20th century, survived the "negative results" that have shown the limits of the axiomatic approach since the 1930s. Rigour, abstraction and symbolism have been confused with formalism, based on finite strings of signs, pre-given axioms, and potentially mechanisable rewriting rules. This contributed to major clarifications in the mathematical praxes but obscured the limits of formalisms due to the exclusion of the historical creation of sense proper to any science. We expand on this sometimes fruitful confusion with some case studies. We then hint to the historical creation of sense as a component of an epistemology of mathematics. We continue with an analogy with genocentric approaches in biology, as similar positivistic views resurfaced there fifty years later. Finite sequences of letters in the DNA would completely determine ontogenesis and phylogenesis, according to the Central Dogma of molecular biology. Limits and "negative evidence" have been disregarded while searching for the "gene for" everything. Alternative perspectives require a reconstruction of the sense of history as locus for the constitution of any object of biological knowledge. In particular, the historicity of biological evolution will be understood in terms of changing phase spaces and of the role of rare events in all phylogenetic trajectories. The analysis of the evolutionary production of variability, adaptivity and ecosystemic diversity is a key component of the project we hint to, as part of a renewed relation to the biological environment.Cell migration and cell proliferation are the basic principles that make up a living organism, and both biologically and medically. In order to understand living organism and biological phenomena, it is essential to track the migration, proliferation, and fate of cells in living cells and animals and to clarify the properties and molecular expression of cells. Recent developments in novel fluorescent proteins have made it possible to observe cell migration and proliferation as the cell cycle at the single-cell level in living individuals and tissues. Here, we introduce cell cycle visualization of living cells and animals by Fucci (Fluorescent Ubiquitination-based Cell Cycle Indicator) system and in situ cell labeling of cells and tracking cell migration by photoactivatable and photoconvertible proteins. In addition, we will present our established methods as an example of combines above tools with single-cell molecular expression analysis to reveal the fate of migrating cells at single cell level.The Allen Human Brain Atlas (AHBA) is the first example of human brain transcriptomic mappings and detailed anatomical annotations which, for the first time, has allowed the integration of human brain transcriptomics with neuroimaging. This has been made possible because the AHBA offered an original dataset that contains mRNA expression measures for >20,000 genes covering the whole brain and, critically, in a standard stereotaxic space. In recent years many different methods have been used to integrate this data set with brain imaging data, although this endeavour has lacked harmony in terms of the workflow of data processing and subsequent analyses. In this work we discuss five main issues that experience has highlighted as in need of thorough consideration when integrating the AHBA with neuroimaging. These concerns are corroborated by comparing the performance of three different publicly available methods in correlating the same measures of serotonin receptors density with the correspondent AHBA mRNA maps. In this representative case, we were able to show how these methods can lead to discrepant results, suggesting that processing options are not neutral. We believe that the field should take into serious consideration these issues as they could undermine reproducibility and, in the end, the intrinsic value of the AHBA. We also advise on possible strategies to overcome these discrepancies. Finally, we encourage authors towards practices that will improve reproducibility such as transparency in reporting, algorithm and data sharing, collaboration.
During listerial invasion of host cells, these membrane defects can disrupt phagosome membranes, allowing bacteria to escape into the cytosol and rapidly multiply. The activity of listeriolysin O is profoundly dependent on the amount and accessibility of cholesterol in the lipid membrane, which can be modulated by the phospholipase PlcB. All these prominent features of listeriolysin O play a role during different stages of the L. monocytogenes life cycle by promoting the proliferation of the pathogen while mitigating excessive damage to its replicative niche in the cytosol of the host cell.In a series of lectures given in 2003, soon after receiving the Fields Medal for his results in the Algebraic Geometry, Vladimir Voevodsky (1966-2017) identifies two strategic goals for mathematics, which he plans to pursue in his further research. https://www.selleckchem.com/products/stf-083010.html The first goal is to develop a ''computerised library of mathematical knowledge,'' which supports an automated proof-verification. The second goal is to ''bridge pure and applied mathematics.'' Voevodsky's research towards the first goal brought about the new Univalent foundations of mathematics. In view of the second goal Voevodsky in 2004 started to develop a mathematical theory of Population Dynamics, which involved the Categorical Probability theory. This latter project did not bring published results and was abandoned by Voevodsky in 2009 when he decided to focus his efforts on the Univalent foundations and closely related topics. In the present paper, which is based on Voevodsky's archival sources, I present Voevodsky's views of mathematics and its relationships with natural sciences, critically discuss these views, and suggest how Voevodsky's ideas and approaches in the applied mathematics can be further developed and pursued. A special attention is given to Voevodsky's original strategy to bridge the persisting gap between pure and applied mathematics where computers and the computer-assisted mathematics play a major role.The positivistic views that dominated the early debate on the foundations of mathematics, at the beginning of the 20th century, survived the "negative results" that have shown the limits of the axiomatic approach since the 1930s. Rigour, abstraction and symbolism have been confused with formalism, based on finite strings of signs, pre-given axioms, and potentially mechanisable rewriting rules. This contributed to major clarifications in the mathematical praxes but obscured the limits of formalisms due to the exclusion of the historical creation of sense proper to any science. We expand on this sometimes fruitful confusion with some case studies. We then hint to the historical creation of sense as a component of an epistemology of mathematics. We continue with an analogy with genocentric approaches in biology, as similar positivistic views resurfaced there fifty years later. Finite sequences of letters in the DNA would completely determine ontogenesis and phylogenesis, according to the Central Dogma of molecular biology. Limits and "negative evidence" have been disregarded while searching for the "gene for" everything. Alternative perspectives require a reconstruction of the sense of history as locus for the constitution of any object of biological knowledge. In particular, the historicity of biological evolution will be understood in terms of changing phase spaces and of the role of rare events in all phylogenetic trajectories. The analysis of the evolutionary production of variability, adaptivity and ecosystemic diversity is a key component of the project we hint to, as part of a renewed relation to the biological environment.Cell migration and cell proliferation are the basic principles that make up a living organism, and both biologically and medically. In order to understand living organism and biological phenomena, it is essential to track the migration, proliferation, and fate of cells in living cells and animals and to clarify the properties and molecular expression of cells. Recent developments in novel fluorescent proteins have made it possible to observe cell migration and proliferation as the cell cycle at the single-cell level in living individuals and tissues. Here, we introduce cell cycle visualization of living cells and animals by Fucci (Fluorescent Ubiquitination-based Cell Cycle Indicator) system and in situ cell labeling of cells and tracking cell migration by photoactivatable and photoconvertible proteins. In addition, we will present our established methods as an example of combines above tools with single-cell molecular expression analysis to reveal the fate of migrating cells at single cell level.The Allen Human Brain Atlas (AHBA) is the first example of human brain transcriptomic mappings and detailed anatomical annotations which, for the first time, has allowed the integration of human brain transcriptomics with neuroimaging. This has been made possible because the AHBA offered an original dataset that contains mRNA expression measures for >20,000 genes covering the whole brain and, critically, in a standard stereotaxic space. In recent years many different methods have been used to integrate this data set with brain imaging data, although this endeavour has lacked harmony in terms of the workflow of data processing and subsequent analyses. In this work we discuss five main issues that experience has highlighted as in need of thorough consideration when integrating the AHBA with neuroimaging. These concerns are corroborated by comparing the performance of three different publicly available methods in correlating the same measures of serotonin receptors density with the correspondent AHBA mRNA maps. In this representative case, we were able to show how these methods can lead to discrepant results, suggesting that processing options are not neutral. We believe that the field should take into serious consideration these issues as they could undermine reproducibility and, in the end, the intrinsic value of the AHBA. We also advise on possible strategies to overcome these discrepancies. Finally, we encourage authors towards practices that will improve reproducibility such as transparency in reporting, algorithm and data sharing, collaboration.
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