Journal articles: 'Systems biology investigation'

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Fernandes, Marco, and Holger Husi. "Integrative Systems Biology Investigation of Fabry Disease." Diseases 4, no. 4 (November 15, 2016): 35. http://dx.doi.org/10.3390/diseases4040035.

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King, Ross D., Maria Liakata, Chuan Lu, Stephen G. Oliver, and Larisa N. Soldatova. "On the formalization and reuse of scientific research." Journal of The Royal Society Interface 8, no. 63 (April 13, 2011): 1440–48. http://dx.doi.org/10.1098/rsif.2011.0029.

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The reuse of scientific knowledge obtained from one investigation in another investigation is basic to the advance of science. Scientific investigations should therefore be recorded in ways that promote the reuse of the knowledge they generate. The use of logical formalisms to describe scientific knowledge has potential advantages in facilitating such reuse. Here, we propose a formal framework for using logical formalisms to promote reuse. We demonstrate the utility of this framework by using it in a worked example from biology: demonstrating cycles of investigation formalization [ F ] and reuse [ R ] to generate new knowledge. We first used logic to formally describe a Robot scientist investigation into yeast ( Saccharomyces cerevisiae ) functional genomics [ f 1 ]. With Robot scientists, unlike human scientists, the production of comprehensive metadata about their investigations is a natural by-product of the way they work. We then demonstrated how this formalism enabled the reuse of the research in investigating yeast phenotypes [ r 1 = R ( f 1 )]. This investigation found that the removal of non-essential enzymes generally resulted in enhanced growth. The phenotype investigation was then formally described using the same logical formalism as the functional genomics investigation [ f 2 = F ( r 1 )]. We then demonstrated how this formalism enabled the reuse of the phenotype investigation to investigate yeast systems-biology modelling [ r 2 = R ( f 2 )]. This investigation found that yeast flux-balance analysis models fail to predict the observed changes in growth. Finally, the systems biology investigation was formalized for reuse in future investigations [ f 3 = F ( r 2 )]. These cycles of reuse are a model for the general reuse of scientific knowledge.

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Smith, Maren L., and Mark P. Styczynski. "Systems Biology-Based Investigation of Host–Plasmodium Interactions." Trends in Parasitology 34, no. 7 (July 2018): 617–32. http://dx.doi.org/10.1016/j.pt.2018.04.003.

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Zou, Jun, Ming-Wu Zheng, Gen Li, and Zhi-Guang Su. "Advanced Systems Biology Methods in Drug Discovery and Translational Biomedicine." BioMed Research International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/742835.

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Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

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Hogstrand, C., T. S. Carroll, J. D. Rasinger, V. Reffatto, A. K. Lundebye, M. Haave, R. Tassinari, et al. "Systems biology investigation of the mechanisms of brominated flame retardant neurotoxicity." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 157 (September 2010): S4. http://dx.doi.org/10.1016/j.cbpa.2010.06.009.

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Purohit, Vinee, Allon Wagner, Nir Yosef, and Vijay K. Kuchroo. "Systems-based approaches to study immunometabolism." Cellular & Molecular Immunology 19, no. 3 (February 4, 2022): 409–20. http://dx.doi.org/10.1038/s41423-021-00783-9.

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AbstractTechnical advances at the interface of biology and computation, such as single-cell RNA-sequencing (scRNA-seq), reveal new layers of complexity in cellular systems. An emerging area of investigation using the systems biology approach is the study of the metabolism of immune cells. The diverse spectra of immune cell phenotypes, sparsity of immune cell numbers in vivo, limitations in the number of metabolites identified, dynamic nature of cellular metabolism and metabolic fluxes, tissue specificity, and high dependence on the local milieu make investigations in immunometabolism challenging, especially at the single-cell level. In this review, we define the systemic nature of immunometabolism, summarize cell- and system-based approaches, and introduce mathematical modeling approaches for systems interrogation of metabolic changes in immune cells. We close the review by discussing the applications and shortcomings of metabolic modeling techniques. With systems-oriented studies of metabolism expected to become a mainstay of immunological research, an understanding of current approaches toward systems immunometabolism will help investigators make the best use of current resources and push the boundaries of the discipline.

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Ori, Alessandro, Mark C. Wilkinson, and David G. Fernig. "A Systems Biology Approach for the Investigation of the Heparin/Heparan Sulfate Interactome." Journal of Biological Chemistry 286, no. 22 (March 30, 2011): 19892–904. http://dx.doi.org/10.1074/jbc.m111.228114.

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A large body of evidence supports the involvement of heparan sulfate (HS) proteoglycans in physiological processes such as development and diseases including cancer and neurodegenerative disorders. The role of HS emerges from its ability to interact and regulate the activity of a vast number of extracellular proteins including growth factors and extracellular matrix components. A global view on how protein-HS interactions influence the extracellular proteome and, consequently, cell function is currently lacking. Here, we systematically investigate the functional and structural properties that characterize HS-interacting proteins and the network they form. We collected 435 human proteins interacting with HS or the structurally related heparin by integrating literature-derived and affinity proteomics data. We used this data set to identify the topological features that distinguish the heparin/HS-interacting network from the rest of the extracellular proteome and to analyze the enrichment of gene ontology terms, pathways, and domain families in heparin/HS-binding proteins. Our analysis revealed that heparin/HS-binding proteins form a highly interconnected network, which is functionally linked to physiological and pathological processes that are characteristic of higher organisms. Therefore, we then investigated the existence of a correlation between the expansion of domain families characteristic of the heparin/HS interactome and the increase in biological complexity in the metazoan lineage. A strong positive correlation between the expansion of the heparin/HS interactome and biosynthetic machinery and organism complexity emerged. The evolutionary role of HS was reinforced by the presence of a rudimentary HS biosynthetic machinery in a unicellular organism at the root of the metazoan lineage.

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Asnaashari, Solmaz, Elham Amjad, and Babak Sokouti. "A comprehensive investigation on liver regeneration: a meta-analysis and systems biology approach." Clinical and Experimental Hepatology 7, no. 2 (2021): 183–90. http://dx.doi.org/10.5114/ceh.2021.107564.

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Caberlotto, Laura, and Thanh-Phuong Nguyen. "A systems biology investigation of neurodegenerative dementia reveals a pivotal role of autophagy." BMC Systems Biology 8, no. 1 (2014): 65. http://dx.doi.org/10.1186/1752-0509-8-65.

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Figeac, Nicolas, Malgorzata Daczewska, Christophe Marcelle, and Krzysztof Jagla. "Muscle stem cells and model systems for their investigation." Developmental Dynamics 236, no. 12 (2007): 3332–42. http://dx.doi.org/10.1002/dvdy.21345.

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Baghaei, Kaveh, Nazanin Hosseinkhan, Hamid Asadzadeh Aghdaei, and M. R. Zali. "Investigation of a common gene expression signature in gastrointestinal cancers using systems biology approaches." Molecular BioSystems 13, no. 11 (2017): 2277–88. http://dx.doi.org/10.1039/c7mb00450h.

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Lai, Xin, Martin Eberhardt, Ulf Schmitz, and Julio Vera. "Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer." Nucleic Acids Research 47, no. 15 (July 24, 2019): 7753–66. http://dx.doi.org/10.1093/nar/gkz638.

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Abstract MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by suppressing mRNA translation and reducing mRNA stability. A miRNA can potentially bind many mRNAs, thereby affecting the expression of oncogenes and tumor suppressor genes as well as the activity of whole pathways. The promise of miRNA therapeutics in cancer is to harness this evolutionarily conserved mechanism for the coordinated regulation of gene expression, and thus restoring a normal cell phenotype. However, the promiscuous binding of miRNAs can provoke unwanted off-target effects, which are usually caused by high-dose single-miRNA treatments. Thus, it is desirable to develop miRNA therapeutics with increased specificity and efficacy. To achieve that, we propose the concept of miRNA cooperativity in order to exert synergistic repression on target genes, thus lowering the required total amount of miRNAs. We first review miRNA therapies in clinical application. Next, we summarize the knowledge on the molecular mechanism and biological function of miRNA cooperativity and discuss its application in cancer therapies. We then propose and discuss a systems biology approach to investigate miRNA cooperativity for the clinical setting. Altogether, we point out the potential of miRNA cooperativity to reduce off-target effects and to complement conventional, targeted, or immune-based therapies for cancer.

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Karle, Jerome. "Some developments in anomalous dispersion for the structural investigation of macromolecular systems in biology." International Journal of Quantum Chemistry 18, S7 (June 19, 2009): 357–67. http://dx.doi.org/10.1002/qua.560180734.

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Misirli, Goksel, Anil Wipat, Joseph Mullen, Katherine James, Matthew Pocock, Wendy Smith, Nick Allenby, and Jennifer S. Hallinan. "BacillOndex: An Integrated Data Resource for Systems and Synthetic Biology." Journal of Integrative Bioinformatics 10, no. 2 (June 1, 2013): 103–16. http://dx.doi.org/10.1515/jib-2013-224.

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Summary BacillOndex is an extension of the Ondex data integration system, providing a semantically annotated, integrated knowledge base for the model Gram-positive bacterium Bacillus subtilis. This application allows a user to mine a variety of B. subtilis data sources, and analyse the resulting integrated dataset, which contains data about genes, gene products and their interactions. The data can be analysed either manually, by browsing using Ondex, or computationally via a Web services interface. We describe the process of creating a BacillOndex instance, and describe the use of the system for the analysis of single nucleotide polymorphisms in B. subtilis Marburg. The Marburg strain is the progenitor of the widely-used laboratory strain B. subtilis 168. We identified 27 SNPs with predictable phenotypic effects, including genetic traits for known phenotypes. We conclude that BacillOndex is a valuable tool for the systems-level investigation of, and hypothesis generation about, this important biotechnology workhorse. Such understanding contributes to our ability to construct synthetic genetic circuits in this organism.

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Mathur, Melina, Joy S. Xiang, and Christina D. Smolke. "Mammalian synthetic biology for studying the cell." Journal of Cell Biology 216, no. 1 (December 8, 2016): 73–82. http://dx.doi.org/10.1083/jcb.201611002.

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Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology.

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Seldin, Marcus M., and Aldons J. Lusis. "Systems-based approaches for investigation of inter-tissue communication." Journal of Lipid Research 60, no. 3 (January 7, 2019): 450–55. http://dx.doi.org/10.1194/jlr.s090316.

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Hricovíni, Miloš, Raymond J. Owens, Andrzej Bak, Violetta Kozik, Witold Musiał, Roberta Pierattelli, Magdaléna Májeková, et al. "Chemistry towards Biology—Instruct: Snapshot." International Journal of Molecular Sciences 23, no. 23 (November 26, 2022): 14815. http://dx.doi.org/10.3390/ijms232314815.

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The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.

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Cheng, Feixiong, James L. Murray, Junfei Zhao, Jinsong Sheng, Zhongming Zhao, and Donald H. Rubin. "Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis." PLOS Computational Biology 12, no. 9 (September 15, 2016): e1005074. http://dx.doi.org/10.1371/journal.pcbi.1005074.

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Ward, Bradley, Jean Cyr Yombi, Jean-Luc Balligand, Patrice D. Cani, Jean-François Collet, Julien de Greef, Joseph P. Dewulf, et al. "HYGIEIA: HYpothesizing the Genesis of Infectious Diseases and Epidemics through an Integrated Systems Biology Approach." Viruses 14, no. 7 (June 23, 2022): 1373. http://dx.doi.org/10.3390/v14071373.

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More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care.

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Privalov, Peter L. "Thermodynamic problems in structural molecular biology." Pure and Applied Chemistry 79, no. 8 (January 1, 2007): 1445–62. http://dx.doi.org/10.1351/pac200779081445.

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The most essential feature of living biological systems is their high degree of structural organization. The key role is played by two linear heteropolymers, the proteins and nucleic acids. Under environmental conditions close to physiological, these biopolymers are folded into unique native conformations, genetically determined by the arrangement of their standard building blocks. In their native conformation, biological macromolecules recognize their partners and associate with them, forming specific, higher-order complexes, the "molecular machines". Folding of biopolymers into their native conformation and their association with partners is in principle a reversible, thermodynamically driven process. Investigation of the thermodynamics of these basic biological processes has prime importance for understanding the mechanisms of forming these supra-macromolecular constructions and their functioning.

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Stevens, A., C. De Leonibus, D. Hanson, A. W. Dowsey, A. Whatmore, S. Meyer, R. P. Donn, et al. "Network analysis: a new approach to study endocrine disorders." Journal of Molecular Endocrinology 52, no. 1 (October 1, 2013): R79—R93. http://dx.doi.org/10.1530/jme-13-0112.

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Systems biology is the study of the interactions that occur between the components of individual cells – including genes, proteins, transcription factors, small molecules, and metabolites, and their relationships to complex physiological and pathological processes. The application of systems biology to medicine promises rapid advances in both our understanding of disease and the development of novel treatment options. Network biology has emerged as the primary tool for studying systems biology as it utilises the mathematical analysis of the relationships between connected objects in a biological system and allows the integration of varied ‘omic’ datasets (including genomics, metabolomics, proteomics, etc.). Analysis of network biology generates interactome models to infer and assess function; to understand mechanisms, and to prioritise candidates for further investigation. This review provides an overview of network methods used to support this research and an insight into current applications of network analysis applied to endocrinology. A wide spectrum of endocrine disorders are included ranging from congenital hyperinsulinism in infancy, through childhood developmental and growth disorders, to the development of metabolic diseases in early and late adulthood, such as obesity and obesity-related pathologies. In addition to providing a deeper understanding of diseases processes, network biology is also central to the development of personalised treatment strategies which will integrate pharmacogenomics with systems biology of the individual.

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van der Kamp, Marc W., Katherine E. Shaw, Christopher J. Woods, and Adrian J. Mulholland. "Biomolecular simulation and modelling: status, progress and prospects." Journal of The Royal Society Interface 5, suppl_3 (July 8, 2008): 173–90. http://dx.doi.org/10.1098/rsif.2008.0105.focus.

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Molecular simulation is increasingly demonstrating its practical value in the investigation of biological systems. Computational modelling of biomolecular systems is an exciting and rapidly developing area, which is expanding significantly in scope. A range of simulation methods has been developed that can be applied to study a wide variety of problems in structural biology and at the interfaces between physics, chemistry and biology. Here, we give an overview of methods and some recent developments in atomistic biomolecular simulation. Some recent applications and theoretical developments are highlighted.

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Blasie, J. Kent, and Peter Timmins. "Neutron Scattering in Structural Biology and Biomolecular Materials." MRS Bulletin 24, no. 12 (December 1999): 40–47. http://dx.doi.org/10.1557/s0883769400053719.

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The substantial power of both elastic and inelastic neutron-scattering techniques for the investigation of the structure and dynamics of biological systems and related biomolecular-based materials—as with soft matter in the previous article by Lindner and Wignall—arises primarily from the essentially isomorphous nature of the substitution of deuterium for selected hydrogen atoms in these systems, coupled with the exquisite sensitivity of neutron scattering to this isotopic substitution. Since these systems are comprised of large macromolecules and supramolecular assemblies thereof, their essential structures and dynamics extend from the atomic scale up to very large length scales of the Order of 101–104 Å. Hence neutron sources and neutron-scattering spectrometers optimized for longer wavelength (or “cold”) thermal neutrons are necessary in order to most effectively address the structure and dynamics at the longer length scales inherent to these Systems.The large majority of previous neutron-scattering experiments on biological systems have been performed with reactor neutron sources. Some of the more significant of these are briefly summarized in the following sections. They may be categorized in terms of the nature of the intermolecular order, both orientational and positional, within the System of interest and either the elastic neutron-scattering technique employed to investigate their time-averaged structures or the inelastic neutron-scattering technique employed to investigate their dynamics.

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Ravera, Enrico, Azzurra Carlon, Marco Fragai, Giacomo Parigi, and Claudio Luchinat. "Paramagnetic NMR as a new tool in structural biology." Emerging Topics in Life Sciences 2, no. 1 (February 6, 2018): 19–28. http://dx.doi.org/10.1042/etls20170084.

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NMR (nuclear magnetic resonance) investigation through the exploitation of paramagnetic effects is passing from an approach limited to few specialists in the field to a generally applicable method that must be considered, especially for the characterization of systems hardly affordable with other techniques. This is mostly due to the fact that paramagnetic data are long range in nature, thus providing information for the structural and dynamic characterization of complex biomolecular architectures in their native environment. On the other hand, this information usually needs to be complemented by data from other sources. Integration of paramagnetic NMR with other techniques, and the development of protocols for a joint analysis of all available data, is fundamental for achieving a comprehensive characterization of complex biological systems. We describe here a few examples of the new possibilities offered by paramagnetic data used in integrated structural approaches.

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Christov, Chr, Chr Balarew, S. Petrenko, and Vl Valyashko. "Investigation of the aqueous lithium and magnesium halide systems." Journal of Solution Chemistry 23, no. 5 (May 1994): 595–604. http://dx.doi.org/10.1007/bf00972747.

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Cook, Brian N., and Carolyn R. Bertozzi. "Chemical approaches to the investigation of cellular systems." Bioorganic & Medicinal Chemistry 10, no. 4 (April 2002): 829–40. http://dx.doi.org/10.1016/s0968-0896(01)00376-5.

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Sima, Felix, and Koji Sugioka. "Ultrafast laser manufacturing of nanofluidic systems." Nanophotonics 10, no. 9 (June 11, 2021): 2389–406. http://dx.doi.org/10.1515/nanoph-2021-0159.

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Abstract In the last decades, research and development of microfluidics have made extraordinary progress, since they have revolutionized the biological and chemical fields as a backbone of lab-on-a-chip systems. Further advancement pushes to miniaturize the architectures to nanoscale in terms of both the sizes and the fluid dynamics for some specific applications including investigation of biological sub-cellular aspects and chemical analysis with much improved detection limits. In particular, nano-scale channels offer new opportunities for tests at single cell or even molecular levels. Thus, nanofluidics, which is a microfluidic system involving channels with nanometer dimensions typically smaller than several hundred nm, has been proposed as an ideal platform for investigating fundamental molecular events at the cell-extracellular milieu interface, biological sensing, and more recently for studying cancer cell migration in a space much narrower than the cell size. In addition, nanofluidics can be used for sample manipulation in analytical chemistry, such as sample injections, separation, purifications or for quantitative and qualitative determinations. Among the nanofabrication technologies, ultrafast laser manufacturing is a promising tool for fabrication of nanofluidics due to its flexibility, versatility, high fabrication resolution and three dimensional (3D) fabrication capability. In this paper, we review the technological advancements of nanofluidic systems, with emphasis on fabrication methods, in particular ultrafast laser manufacturing. We present the challenges for issues concerning channel sizes and fluid dynamics, and introduce the applications in physics, biology, chemistry and engineering with future prospects.

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Fitzgerald, Allison A., Eric Li, and Louis M. Weiner. "3D Culture Systems for Exploring Cancer Immunology." Cancers 13, no. 1 (December 28, 2020): 56. http://dx.doi.org/10.3390/cancers13010056.

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Cancer immunotherapy has revolutionized cancer treatment, spurring extensive investigation into cancer immunology and how to exploit this biology for therapeutic benefit. Current methods to investigate cancer-immune cell interactions and develop novel drug therapies rely on either two-dimensional (2D) culture systems or murine models. However, three-dimensional (3D) culture systems provide a potentially superior alternative model to both 2D and murine approaches. As opposed to 2D models, 3D models are more physiologically relevant and better replicate tumor complexities. Compared to murine models, 3D models are cheaper, faster, and can study the human immune system. In this review, we discuss the most common 3D culture systems—spheroids, organoids, and microfluidic chips—and detail how these systems have advanced our understanding of cancer immunology.

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Liang, Zhongjie, Gennady M. Verkhivker, and Guang Hu. "Integration of network models and evolutionary analysis into high-throughput modeling of protein dynamics and allosteric regulation: theory, tools and applications." Briefings in Bioinformatics 21, no. 3 (March 21, 2019): 815–35. http://dx.doi.org/10.1093/bib/bbz029.

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Abstract Proteins are dynamical entities that undergo a plethora of conformational changes, accomplishing their biological functions. Molecular dynamics simulation and normal mode analysis methods have become the gold standard for studying protein dynamics, analyzing molecular mechanism and allosteric regulation of biological systems. The enormous amount of the ensemble-based experimental and computational data on protein structure and dynamics has presented a major challenge for the high-throughput modeling of protein regulation and molecular mechanisms. In parallel, bioinformatics and systems biology approaches including genomic analysis, coevolution and network-based modeling have provided an array of powerful tools that complemented and enriched biophysical insights by enabling high-throughput analysis of biological data and dissection of global molecular signatures underlying mechanisms of protein function and interactions in the cellular environment. These developments have provided a powerful interdisciplinary framework for quantifying the relationships between protein dynamics and allosteric regulation, allowing for high-throughput modeling and engineering of molecular mechanisms. Here, we review fundamental advances in protein dynamics, network theory and coevolutionary analysis that have provided foundation for rapidly growing computational tools for modeling of allosteric regulation. We discuss recent developments in these interdisciplinary areas bridging computational biophysics and network biology, focusing on promising applications in allosteric regulations, including the investigation of allosteric communication pathways, protein–DNA/RNA interactions and disease mutations in genomic medicine. We conclude by formulating and discussing future directions and potential challenges facing quantitative computational investigations of allosteric regulatory mechanisms in protein systems.

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Harris, David A. "Cellular Biology of Prion Diseases." Clinical Microbiology Reviews 12, no. 3 (July 1, 1999): 429–44. http://dx.doi.org/10.1128/cmr.12.3.429.

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Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on public health and because they exemplify a novel mechanism of infectivity and biological information transfer. These diseases are caused by conformational conversion of a normal host glycoprotein (PrPC) into an infectious isoform (PrPSc) that is devoid of nucleic acid. This review focuses on the current understanding of prion diseases at the cell biological level. The characteristics of the diseases are introduced, and a brief history and description of the prion hypothesis are given. Information is then presented about the structure, expression, biosynthesis, and possible function of PrPC, as well as its posttranslational processing, cellular localization, and trafficking. The latest findings concerning PrPSc are then discussed, including cell culture systems used to generate this pathogenic isoform, the subcellular distribution of the protein, its membrane attachment, proteolytic processing, and its kinetics and sites of synthesis. Information is also provided on molecular models of the PrPC→PrPSc conversion reaction and the possible role of cellular chaperones. The review concludes with suggestions of several important avenues for future investigation.

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Mack, Sean G., Daniel J. Cook, Prasad Dhurjati, and Matthew E. R. Butchbach. "Systems Biology Investigation of cAMP Modulation to Increase SMN Levels for the Treatment of Spinal Muscular Atrophy." PLoS ONE 9, no. 12 (December 16, 2014): e115473. http://dx.doi.org/10.1371/journal.pone.0115473.

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Sertbaş, Mustafa, Kutlu Ülgen, and Tunahan Çakır. "Investigation of The Effects of Neurological Diseases on Human Brain Metabolism by A Computational Systems Biology Approach." New Biotechnology 29 (September 2012): S150. http://dx.doi.org/10.1016/j.nbt.2012.08.416.

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Sehgal, Manika, and Tiratha Raj Singh. "Systems biology approach for mutational and site-specific structural investigation of DNA repair genes for xeroderma pigmentosum." Gene 543, no. 1 (June 2014): 108–17. http://dx.doi.org/10.1016/j.gene.2014.03.057.

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Taylor, Charles, and David Jefferson. "Artificial Life as a Tool for Biological Inquiry." Artificial Life 1, no. 1_2 (October 1993): 1–13. http://dx.doi.org/10.1162/artl.1993.1.1_2.1.

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Artificial life embraces those human-made systems that possess some of the key properties of natural life. We are specifically interested in artificial systems that serve as models of living systems for the investigation of open questions in biology. First we review some of the artificial life models that have been constructed with biological problems in mind, and classify them by medium (hardware, software, or “wetware”) and by level of organization (molecular, cellular, organismal, or population). We then describe several “grand challenge” open problems in biology that seem especially good candidates to benefit from artificial life studies, including the origin of life and self-organi- zation, cultural evolution, origin and maintenance of sex, shifting balance in evolution, the relation between fitness and adaptedness, the structure of ecosystems, and the nature of mind.

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Matsuno, Seigo, Takao Ito, and Zengyu Xia. "Determinants of information systems outsourcing: an empirical investigation in Japan." Artificial Life and Robotics 14, no. 3 (December 2009): 337–41. http://dx.doi.org/10.1007/s10015-009-0677-y.

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Lai, Michael W., Nathan Chow, Antonio Checco, Balvir Kunar, David Redmond, Shahin Rafii, and Sina Y. Rabbany. "Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch." Biomolecules 12, no. 12 (December 8, 2022): 1837. http://dx.doi.org/10.3390/biom12121837.

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Endothelial cells in vivo are subjected to a wide array of mechanical stimuli, such as cyclic stretch. Notably, a 10% stretch is associated with an atheroprotective endothelial phenotype, while a 20% stretch is associated with an atheroprone endothelial phenotype. Here, a systems biology-based approach is used to present a comprehensive overview of the functional responses and molecular regulatory networks that characterize the transition from an atheroprotective to an atheroprone phenotype in response to cyclic stretch. Using primary human umbilical vein endothelial cells (HUVECs), we determined the role of the equibiaxial cyclic stretch in vitro, with changes to the radius of the magnitudes of 10% and 20%, which are representative of physiological and pathological strain, respectively. Following the transcriptome analysis of next-generation sequencing data, we identified four key endothelial responses to pathological cyclic stretch: cell cycle regulation, inflammatory response, fatty acid metabolism, and mTOR signaling, driven by a regulatory network of eight transcription factors. Our study highlights the dynamic regulation of several key stretch-sensitive endothelial functions relevant to the induction of an atheroprone versus an atheroprotective phenotype and lays the foundation for further investigation into the mechanisms governing vascular pathology. This study has significant implications for the development of treatment modalities for vascular disease.

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Brammer, R. J., T. N. Bryant, and J. H. R. May. "Investigation of an expert systems approach to bacterial identification." Bioinformatics 7, no. 4 (1991): 461–69. http://dx.doi.org/10.1093/bioinformatics/7.4.461.

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Emons, H. H., H. Jahn, and G. Wolf. "Investigation of salt ? Mixed solvent systems. XXXVII. Crystallization enthalpy of lithium chloride in mixed solvent systems." Journal of Solution Chemistry 19, no. 5 (May 1990): 437–46. http://dx.doi.org/10.1007/bf00650376.

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Singh, Pallavi. "APPLICATION OF SYSTEMS BIOLOGY APPROACH FOR INVESTIGATION OF PAN GENOME AND PHYLOGENETICS IN VARIOUS STRAINS OF ANAPLASMA PHAGOCYTOPHILUM." Journal of Microbiology, Biotechnology and Food Sciences 10, no. 3 (December 1, 2020): 445–48. http://dx.doi.org/10.15414/jmbfs.2020.10.3.445-448.

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Jasti, Bhaskara R., and William Abraham. "Fluorescence Spectroscopic Investigation of Effect of Excipients on Epidermal Barrier and Transdermal Systems." Journal of Investigative Dermatology Symposium Proceedings 3, no. 2 (August 1998): 128–30. http://dx.doi.org/10.1038/jidsymp.1998.26.

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LoVullo, Eric D., Claudia R. Molins-Schneekloth, Herbert P. Schweizer, and Martin S. Pavelka. "Single-copy chromosomal integration systems for Francisella tularensis." Microbiology 155, no. 4 (April 1, 2009): 1152–63. http://dx.doi.org/10.1099/mic.0.022491-0.

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Francisella tularensis is a fastidious Gram-negative bacterium responsible for the zoonotic disease tularemia. Investigation of the biology and molecular pathogenesis of F. tularensis has been limited by the difficulties in manipulating such a highly pathogenic organism and by a lack of genetic tools. However, recent advances have substantially improved the ability of researchers to genetically manipulate this organism. To expand the molecular toolbox we have developed two systems to stably integrate genetic elements in single-copy into the F. tularensis genome. The first system is based upon the ability of transposon Tn7 to insert in both a site- and orientation-specific manner at high frequency into the attTn7 site located downstream of the highly conserved glmS gene. The second system consists of a sacB-based suicide plasmid used for allelic exchange of unmarked elements with the blaB gene, encoding a β-lactamase, resulting in the replacement of blaB with the element and the loss of ampicillin resistance. To test these new tools we used them to complement a novel d-glutamate auxotroph of F. tularensis LVS, created using an improved sacB-based allelic exchange plasmid. These new systems will be helpful for the genetic manipulation of F. tularensis in studies of tularemia biology, especially where the use of multi-copy plasmids or antibiotic markers may not be suitable.

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CHEN, JAKE Y., ZHONG YAN, CHANGYU SHEN, DAWN P. G. FITZPATRICK, and MU WANG. "A SYSTEMS BIOLOGY APPROACH TO THE STUDY OF CISPLATIN DRUG RESISTANCE IN OVARIAN CANCERS." Journal of Bioinformatics and Computational Biology 05, no. 02a (April 2007): 383–405. http://dx.doi.org/10.1142/s0219720007002606.

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Cisplatin-induced drug resistance is known to involve a complex set of cellular changes whose molecular mechanism details remain unclear. In this study, we developed a systems biology approach to examine proteomics- and network-level changes between cisplatin-resistant and cisplatin-sensitive cell lines. This approach involves experimental investigation of differential proteomics profiles and computational study of activated enriched proteins, protein interactions, and protein interaction networks. Our experimental platform is based on a Label-free liquid Chromatography/mass spectrometry proteomics platform. Our computational methods start with an initial list of 119 differentially expressed proteins. We expanded these proteins into a cisplatin-resistant activated sub-network using a database of human protein-protein interactions. An examination of network topology features revealed the activated responses in the network are closely coupled. By examining sub-network proteins using gene ontology categories, we found significant enrichment of proton-transporting ATPase and ATP synthase complexes activities in cisplatin-resistant cells in the form of cooperative down-regulations. Using two-dimensional visualization matrixes, we further found significant cascading of endogenous, abiotic, and stress-related signals. Using a visual representation of activated protein categorical sub-networks, we showed that molecular regulation of cell differentiation and development caused by responses to proteome-wide stress as a key signature to the acquired drug resistance.

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Korma, V. D. "The Use of Catastrophe Theory in Forensics." Actual Problems of Russian Law 17, no. 12 (October 6, 2022): 204–12. http://dx.doi.org/10.17803/1994-1471.2022.145.12.204-212.

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The modern theory of catastrophes contributes to the understanding of dynamic situations that govern the evolutionary development of natural phenomena, society, and man, as well as the prediction of the instability of various dynamic systems that can have catastrophic consequences. The results of the development of this theory are widely used in various fields of knowledge: in physics, biology, economics, medicine, psychology, linguistics, ecology and other sciences. The paper attempts to use the theory of catastrophes in forensic science, in particular, in the investigation of criminally relevant incidents of a man-made nature related to professional activities, which are inherently a destructive product of the functioning of various dynamic systems. First, the theoretical aspects of the theory of catastrophes are briefly outlined, the main concepts and their classifications are considered (catastrophe, man-made disaster, man-made emergency, emergencies, man-made sources of increased danger, etc.), which are important for developing a methodology for investigating man-made crimes related to professional activities. In order to improve the efficiency of the investigator’s recognition activity in establishing the cause of the crime under investigation (man-made disaster), the author proposes to use schemes (probabilistic models) obtained using the techniques for constructing the so-called fault and event trees, addressed primarily to specialists associated with the operation of technical systems and supervision behind them. According to the author, this will contribute to the effectiveness of putting forward investigative leads in a criminal case and their verification.

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Atterwill, Christopher K., Wendy J. Davies, and Michael A. Kyriakides. "An Investigation of Aluminium Neurotoxicity using some In Vitro Systems." Alternatives to Laboratory Animals 18, no. 1_part_1 (November 1990): 181–90. http://dx.doi.org/10.1177/026119299001800119.1.

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It has been shown that acute exposure in vitro to high concentrations of aluminium chloride does not appear to perturb neural function in terms of the electrophysiological properties of lower vertebrate leech neurones. Longer term exposure in vitro, however, both non-specifically inhibits cellular differentiation and also produces neural cytotoxicity in the rat midbrain micromass, mixed cell culture model. Furthermore, previous studies from this laboratory have demonstrated a reduction of cholinergic neuronal function in brain organotypic reaggregate cultures following long-term, but not short-term, exposure. More-immature neural cells appear to be most sensitive to the effects of aluminium. Relating these data to the tiered in vitro test system for neurotoxicants previously proposed by Atterwill (13), it is apparent that the neurotoxic effects of aluminium are detectable in a first-stage procedure using the micromass culture model, but not following acute exposure in freshly isolated, ex vivo leech neurones. Functional cholinergic toxicity was also detected in the organotypic reaggregate cultures proposed as a second level screen.

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Madsen, Henriette Baun, Helle M. Arboe-Andersen, Noemi Rozlosnik, Flemming Madsen, Peter Ifversen, Marina R. Kasimova, and Hanne Mørck Nielsen. "Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems." Biochimica et Biophysica Acta (BBA) - Biomembranes 1798, no. 9 (September 2010): 1779–89. http://dx.doi.org/10.1016/j.bbamem.2010.06.006.

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Davidson, Alan R., Wang-Ting Lu, Sabrina Y. Stanley, Jingrui Wang, Marios Mejdani, Chantel N. Trost, Brian T. Hicks, Jooyoung Lee, and Erik J. Sontheimer. "Anti-CRISPRs: Protein Inhibitors of CRISPR-Cas Systems." Annual Review of Biochemistry 89, no. 1 (June 20, 2020): 309–32. http://dx.doi.org/10.1146/annurev-biochem-011420-111224.

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Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying cas (CRISPR-associated) genes are found frequently in bacteria and archaea, serving to defend against invading foreign DNA, such as viral genomes. CRISPR-Cas systems provide a uniquely powerful defense because they can adapt to newly encountered genomes. The adaptive ability of these systems has been exploited, leading to their development as highly effective tools for genome editing. The widespread use of CRISPR-Cas systems has driven a need for methods to control their activity. This review focuses on anti-CRISPRs (Acrs), proteins produced by viruses and other mobile genetic elements that can potently inhibit CRISPR-Cas systems. Discovered in 2013, there are now 54 distinct families of these proteins described, and the functional mechanisms of more than a dozen have been characterized in molecular detail. The investigation of Acrs is leading to a variety of practical applications and is providing exciting new insight into the biology of CRISPR-Cas systems.

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Kamiya, Koki. "Development of Artificial Cell Models Using Microfluidic Technology and Synthetic Biology." Micromachines 11, no. 6 (May 30, 2020): 559. http://dx.doi.org/10.3390/mi11060559.

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Giant lipid vesicles or liposomes are primarily composed of phospholipids and form a lipid bilayer structurally similar to that of the cell membrane. These vesicles, like living cells, are 5–100 μm in diameter and can be easily observed using an optical microscope. As their biophysical and biochemical properties are similar to those of the cell membrane, they serve as model cell membranes for the investigation of the biophysical or biochemical properties of the lipid bilayer, as well as its dynamics and structure. Investigation of membrane protein functions and enzyme reactions has revealed the presence of soluble or membrane proteins integrated in the giant lipid vesicles. Recent developments in microfluidic technologies and synthetic biology have enabled the development of well-defined artificial cell models with complex reactions based on the giant lipid vesicles. In this review, using microfluidics, the formations of giant lipid vesicles with asymmetric lipid membranes or complex structures have been described. Subsequently, the roles of these biomaterials in the creation of artificial cell models including nanopores, ion channels, and other membrane and soluble proteins have been discussed. Finally, the complex biological functions of giant lipid vesicles reconstituted with various types of biomolecules has been communicated. These complex artificial cell models contribute to the production of minimal cells or protocells for generating valuable or rare biomolecules and communicating between living cells and artificial cell models.

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Lafontan, Max. "Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways." American Journal of Physiology-Cell Physiology 302, no. 2 (January 15, 2012): C327—C359. http://dx.doi.org/10.1152/ajpcell.00168.2011.

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For many years, there was little interest in the biochemistry or physiology of adipose tissue. It is now well recognized that adipocytes play an important dynamic role in metabolic regulation. They are able to sense metabolic states via their ability to perceive a large number of nervous and hormonal signals. They are also able to produce hormones, called adipokines, that affect nutrient intake, metabolism and energy expenditure. The report by Rodbell in 1964 that intact fat cells can be obtained by collagenase digestion of adipose tissue revolutionized studies on the hormonal regulation and metabolism of the fat cell. In the context of the advent of systems biology in the field of cell biology, the present seems an appropriate time to look back at the global contribution of the fat cell to cell biology knowledge. This review focuses on the very early approaches that used the fat cell as a tool to discover and understand various cellular mechanisms. Attention essentially focuses on the early investigations revealing the major contribution of mature fat cells and also fat cells originating from adipose cell lines to the discovery of major events related to hormone action (hormone receptors and transduction pathways involved in hormonal signaling) and mechanisms involved in metabolite processing (hexose uptake and uptake, storage, and efflux of fatty acids). Dormant preadipocytes exist in the stroma-vascular fraction of the adipose tissue of rodents and humans; cell culture systems have proven to be valuable models for the study of the processes involved in the formation of new fat cells. Finally, more recent insights into adipocyte secretion, a completely new role with major metabolic impact, are also briefly summarized.

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Litschel, Thomas, and Petra Schwille. "Protein Reconstitution Inside Giant Unilamellar Vesicles." Annual Review of Biophysics 50, no. 1 (May 6, 2021): 525–48. http://dx.doi.org/10.1146/annurev-biophys-100620-114132.

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Giant unilamellar vesicles (GUVs) have gained great popularity as mimicries for cellular membranes. As their sizes are comfortably above the optical resolution limit, and their lipid composition is easily controlled, they are ideal for quantitative light microscopic investigation of dynamic processes in and on membranes. However, reconstitution of functional proteins into the lumen or the GUV membrane itself has proven technically challenging. In recent years, a selection of techniques has been introduced that tremendously improve GUV-assay development and enable the precise investigation of protein–membrane interactions under well-controlled conditions. Moreover, due to these methodological advances, GUVs are considered important candidates as protocells in bottom-up synthetic biology. In this review, we discuss the state of the art of the most important vesicle production and protein encapsulation methods and highlight some key protein systems whose functional reconstitution has advanced the field.

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Niemann, Pia, Miriam Schiffer, Daniela Malan, Sabine Grünberg, Wilhelm Roell, Caroline Geisen, and Bernd K. Fleischmann. "Generation and Characterization of an Inducible Cx43 Overexpression System in Mouse Embryonic Stem Cells." Cells 11, no. 4 (February 16, 2022): 694. http://dx.doi.org/10.3390/cells11040694.

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Connexins (Cx) are a large family of membrane proteins that can form intercellular connections, so-called gap junctions between adjacent cells. Cx43 is widely expressed in mammals and has a variety of different functions, such as the propagation of electrical conduction in the cardiac ventricle. Despite Cx43 knockout models, many questions regarding the biology of Cx43 in health and disease remain unanswered. Herein we report the establishment of a Cre-inducible Cx43 overexpression system in murine embryonic stem (ES) cells. This enables the investigation of the impact of Cx43 overexpression in somatic cells. We utilized a double reporter system to label Cx43-overexpressing cells via mCherry fluorescence and exogenous Cx43 via fusion with P2A peptide to visualize its distribution pattern. We proved the functionality of our systems in ES cells, HeLa cells, and 3T3-fibroblasts and demonstrated the formation of functional gap junctions based on dye diffusion and FRAP experiments. In addition, Cx43-overexpressing ES cells could be differentiated into viable cardiomyocytes, as shown by the formation of cross striation and spontaneous beating. Analysis revealed faster and more rhythmic beating of Cx43-overexpressing cell clusters. Thus, our Cx43 overexpression systems enable the investigation of Cx43 biology and function in cardiomyocytes and other somatic cells.

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Journal articles on the topic 'Systems biology investigation'

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