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Wiley Interdisciplinary Reviews. Systems Biology and Medicine

H Frederik Nijhout, Janet A Best, Michael C Reed
All organisms are subject to large amounts of genetic and environmental variation and have evolved mechanisms that allow them to function well in spite of these challenges. This property is generally referred to as robustness. We start with the premise that phenotypes arise from dynamical systems and are therefore system properties. Phenotypes occur at all levels of the biological organizational hierarchy, from gene products, to biochemical pathways, to cells, tissues, organs, appendages, and whole bodies. Phenotypes at all these levels are subject to environmental and genetic challenges against which their form and function need to be protected...
October 29, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Ameneh Asgari-Targhi, Elizabeth B Klerman
Circadian rhythms are endogenous ~24-hr oscillations usually entrained to daily environmental cycles of light/dark. Many biological processes and physiological functions including mammalian body temperature, the cell cycle, sleep/wake cycles, neurobehavioral performance, and a wide range of diseases including metabolic, cardiovascular, and psychiatric disorders are impacted by these rhythms. Circadian clocks are present within individual cells and at tissue and organismal levels as emergent properties from the interaction of cellular oscillators...
October 17, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Inez Lam, Christina M Pickering, Feilim Mac Gabhann
Receptor tyrosine kinases (RTKs) are cell membrane proteins that provide cells with the ability to sense proteins in their environments. Many RTKs are essential to development and organ growth. Derangement of RTKs-by mutation or by overexpression-is central to several developmental and adult disorders including cancer, short stature, and vascular pathologies. The mechanism of action of RTKs is complex and is regulated by contextual components, including the existence of multiple competing ligands and receptors in many families, the intracellular location of the RTK, the dynamic and cell-specific coexpression of other RTKs, and the commonality of downstream signaling pathways...
September 26, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Ghee Chuan Lai, Tze Guan Tan, Norman Pavelka
Mammalian barrier surfaces are densely populated by symbiont fungi in much the same way the former are colonized by symbiont bacteria. The fungal microbiota, otherwise known as the mycobiota, is increasingly recognized as a critical player in the maintenance of health and homeostasis of the host. Here we discuss the impact of the mycobiota on host physiology and disease, the factors influencing mycobiota composition, and the current technologies used for identifying symbiont fungal species. Understanding the tripartite interactions among the host, mycobiota, and other members of the microbiota, will help to guide the development of novel prevention and therapeutic strategies for a variety of human diseases...
September 25, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Haihan Tan, Wee-Wei Tee
The germ line is a crucial cell lineage that is distinct from somatic cells, and solely responsible for the trans-generational transmission of hereditary information in metazoan sexual reproduction. Primordial germ cells (PGCs)-the precursors to functional germ cells-are among the first cell types to be allocated in embryonic development, and this lineage commitment is a critical event in partitioning germ line and somatic tissues. Classically, mammalian PGC development has been largely informed by investigations on mouse embryos and embryonic stem cells...
September 17, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Michael I Miller, Sylvain Arguillère, Daniel J Tward, Laurent Younes
The nonlinear systems models of computational anatomy that have emerged over the past several decades are a synthesis of three significant areas of computational science and biological modeling. First is the algebraic model of biological shape as a Riemannian orbit, a set of objects under diffeomorphic action. Second is the embedding of anatomical shapes into the soft condensed matter physics continuum via the extension of the Euler equations to geodesic, smooth flows with inverses, encoding divergence for the compressibility of atrophy and expansion of growth...
November 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Dejun Lin, Giancarlo Bonora, Galip Gürkan Yardımcı, William S Noble
Recent advances in chromosome conformation capture technologies have led to the discovery of previously unappreciated structural features of chromatin. Computational analysis has been critical in detecting these features and thereby helping to uncover the building blocks of genome architecture. Algorithms are being developed to integrate these architectural features to construct better three-dimensional (3D) models of the genome. These computational methods have revealed the importance of 3D genome organization to essential biological processes...
July 18, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Stefano Morotti, Eleonora Grandi
Quantitative systems modeling aims to integrate knowledge in different research areas with models describing biological mechanisms and dynamics to gain a better understanding of complex clinical syndromes. Heart failure (HF) is a chronic complex cardiac disease that results from structural or functional disorders impairing the ability of the ventricle to fill with or eject blood. Highly interactive and dynamic changes in mechanical, structural, neurohumoral, metabolic, and electrophysiological properties collectively predispose the failing heart to cardiac arrhythmias, which are responsible for about a half of HF deaths...
July 17, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Evan Tsiklidis, Carrie Sims, Talid Sinno, Scott L Diamond
Trauma with hypovolemic shock is an extreme pathological state that challenges the body to maintain blood pressure and oxygenation in the face of hemorrhagic blood loss. In conjunction with surgical actions and transfusion therapy, survival requires the patient's blood to maintain hemostasis to stop bleeding. The physics of the problem are multiscale: (a) the systemic circulation sets the global blood pressure in response to blood loss and resuscitation therapy, (b) local tissue perfusion is altered by localized vasoregulatory mechanisms and bleeding, and (c) altered blood and vessel biology resulting from the trauma as well as local hemodynamics control the assembly of clotting components at the site of injury...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Magdalena Harakalova, Folkert W Asselbergs
Dilated cardiomyopathy (DCM) is a form of severe failure of cardiac muscle caused by a long list of etiologies ranging from myocardial infarction, DNA mutations in cardiac genes, to toxics. Systems analysis integrating next-generation sequencing (NGS)-based omics approaches, such as the sequencing of DNA, RNA, and chromatin, provide valuable insights into DCM mechanisms. The outcome and interpretation of NGS methods can be affected by the localization of cardiac biopsy, level of tissue degradation, and variable ratios of different cell populations, especially in the presence of fibrosis...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Julia M Barbarino, Michelle Whirl-Carrillo, Russ B Altman, Teri E Klein
As precision medicine becomes increasingly relevant in healthcare, the field of pharmacogenomics (PGx) also continues to gain prominence in the clinical setting. Leading institutions have begun to implement PGx testing and the amount of published PGx literature increases yearly. The Pharmacogenomics Knowledgebase (PharmGKB; is one of the foremost worldwide resources for PGx knowledge, and the organization has been adapting and refocusing its mission along with the current revolution in genomic medicine...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Kevin R Costello, Dustin E Schones
Metabolic diseases such as obesity and diabetes are complex diseases resulting from multiple genetic and environmental factors, such as diet and activity levels. These factors are well known contributors to the development of metabolic diseases. One manner by which environmental factors can influence metabolic disease progression is through modifications to chromatin. These modifications can lead to altered gene regulatory programs, which alters disease risk. Furthermore, there is evidence that parents exposed to environmental factors can influence the metabolic health of offspring, especially if exposures are during intrauterine growth periods...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Makiko Iwafuchi-Doi
Pioneer transcription factors play a primary role in establishing competence for gene expression and initiating cellular programming and reprogramming, and their dysregulation causes severe effects on human health, such as promoting tumorigenesis. Although more than 200 transcription factors are expressed in each cell type, only a small number of transcription factors are necessary to elicit dramatic cell-fate changes in embryonic development and cell-fate conversion. Among these key transcription factors, a subset called "pioneer transcription factors" have a remarkable ability to target nucleosomal DNA, or closed chromatin, early in development, often leading to the local opening of chromatin, thereby establishing competence for gene expression...
June 27, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Xu Lan, Martha S Field, Patrick J Stover
Folate-mediated one-carbon metabolism (FOCM) comprises a network of interconnected folate-dependent metabolic pathways responsible for serine and glycine interconversion, de novo purine synthesis, de novo thymidylate synthesis and homocysteine remethylation to methionine. These pathways are compartmentalized in the cytosol, nucleus and mitochondria. Individual enzymes within the FOCM network compete for folate cofactors because intracellular folate concentrations are limiting. Although there are feedback mechanisms that regulate the partitioning of folate cofactors among the folate-dependent pathways, less recognized is the impact of cell cycle regulation on FOCM...
June 11, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Kathryn R Tringale, John Pang, Quyen T Nguyen
Primary treatment for many solid cancers includes surgical excision or radiation therapy, with or without the use of adjuvant therapy. This can include the addition of radiation and chemotherapy after primary surgical therapy, or the addition of chemotherapy and salvage surgery to primary radiation therapy. Both primary therapies, surgery and radiation, require precise anatomic localization of tumor. If tumor is not targeted adequately with initial treatment, disease recurrence may ensue, and if targeting is too broad, unnecessary morbidity may occur to nearby structures or remaining normal tissue...
May 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Matthew D Wiens, Robert E Campbell
Mapping the protein-protein interaction (PPi) landscape is of critical importance to furthering our understanding how cells and organisms function. Optogenetic methods, that is, approaches that utilize genetically encoded fluorophores or fluorogenic enzyme reactions, uniquely enable the visualization of biochemical phenomena in live cells with high spatial and temporal accuracy. Applying optogenetic methods to the detection of PPis requires the engineering of protein-based systems in which an optical signal undergoes a substantial change when the two proteins of interest interact...
May 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
D Rose Ewald, Susan C J Sumner
Far from being just "bugs in our guts," the microbiota interacts with the body in previously unimagined ways. Research into the genome and the microbiome has revealed that the human body and the microbiota have a long-established but only recently recognized symbiotic relationship; homeostatic balance between them regulates body function. That balance is fragile, easily disturbed, and plays a fundamental role in human health-our very survival depends on the healthy functioning of these microorganisms...
May 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Shao-Shan C Huang, Joseph R Ecker
5-Methylcytosine, a chemical modification of DNA, is a covalent modification found in the genomes of both plants and animals. Epigenetic inheritance of phenotypes mediated by DNA methylation is well established in plants. Most of the known mechanisms of establishing, maintaining and modifying DNA methylation have been worked out in the reference plant Arabidopsis thaliana. Major functions of DNA methylation in plants include regulation of gene expression and silencing of transposable elements (TEs) and repetitive sequences, both of which have parallels in mammalian biology, involve interaction with the transcriptional machinery, and may have profound effects on the regulatory networks in the cell...
May 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Julia M Rogers, Martha L Bulyk
Sequence-specific transcription factors (TFs) bind short DNA sequences in the genome to regulate the expression of target genes. In the last decade, numerous technical advances have enabled the determination of the DNA-binding specificities of many of these factors. Large-scale screens of many TFs enabled the creation of databases of TF DNA-binding specificities, typically represented as position weight matrices (PWMs). Although great progress has been made in determining and predicting binding specificities systematically, there are still many surprises to be found when studying a particular TF's interactions with DNA in detail...
April 25, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Victor Olariu, Carsten Peterson
As cell and molecular biology is becoming increasingly quantitative, there is an upsurge of interest in mechanistic modeling at different levels of resolution. Such models mostly concern kinetics and include gene and protein interactions as well as cell population dynamics. The final goal of these models is to provide experimental predictions, which is now taking on. However, even without matured predictions, kinetic models serve the purpose of compressing a plurality of experimental results into something that can empower the data interpretation, and importantly, suggesting new experiments by turning "knobs" in silico...
April 16, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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