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Wiley Interdisciplinary Reviews. Systems Biology and Medicine

Yoav Hadas, Michael G Katz, Charles R Bridges, Lior Zangi
Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in developed countries. Current pharmacological and interventional therapies provide significant improvement in the life quality of patient; however, they are mostly symptom-oriented and not curative. A high disease and economic burden of IHD requires the search for new therapeutic strategies to significantly improve patients' prognosis and quality of life. One of the main challenges during IHD is the massive loss of cardiomyocytes that possess minimal regenerative capacity...
December 2, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
David S Moore
Why do we grow up to have the traits we do? Most 20th century scientists answered this question by referring only to our genes and our environments. But recent discoveries in the emerging field of behavioral epigenetics have revealed factors at the interface between genes and environments that also play crucial roles in development. These factors affect how genes work; scientists now know that what matters as much as which genes you have (and what environments you encounter) is how your genes are affected by their contexts...
December 1, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Meng Sun, Muhammad H Zaman
Cell migration is a complex and multistep process involved in homeostasis maintenance, morphogenesis, and disease development, such as cancer metastasis. Modeling cell migration and the relevant cytoskeleton dynamics have profound implications for studying fundamental development and disease diagnosis. This review focuses on some recent models of both cell migration and migration-related cytoskeleton dynamics, addressing issues such as the difference between amoeboid and mesenchymal migration modes, and between single-cell migration and collective cell migration...
November 15, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Christos M Dimitrakopoulos, Niko Beerenwinkel
High-throughput DNA sequencing techniques enable large-scale measurement of somatic mutations in tumors. Cancer genomics research aims at identifying all cancer-related genes and solid interpretation of their contribution to cancer initiation and development. However, this venture is characterized by various challenges, such as the high number of neutral passenger mutations and the complexity of the biological networks affected by driver mutations. Based on biological pathway and network information, sophisticated computational methods have been developed to facilitate the detection of cancer driver mutations and pathways...
November 11, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Alys R Clark, Jennifer A Kruger
From ovulation to delivery, and through the menstrual cycle, the female reproductive system undergoes many dynamic changes to provide an optimal environment for the embryo to implant, and to develop successfully. It is difficult ethically and practically to observe the system over the timescales involved in growth and development (often hours to days). Even in carefully monitored conditions clinicians and biologists can only see snapshots of the development process. Mathematical models are emerging as a key means to supplement our knowledge of the reproductive process, and to tease apart complexity in the reproductive system...
September 9, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Felix T Kurz, Jackelyn M Kembro, Ana G Flesia, Antonis A Armoundas, Sonia Cortassa, Miguel A Aon, David Lloyd
Advancing from two core traits of biological systems: multilevel network organization and nonlinearity, we review a host of novel and readily available techniques to explore and analyze their complex dynamic behavior within the framework of experimental-computational synergy. In the context of concrete biological examples, analytical methods such as wavelet, power spectra, and metabolomics-fluxomics analyses, are presented, discussed, and their strengths and limitations highlighted. Further shown is how time series from stationary and nonstationary biological variables and signals, such as membrane potential, high-throughput metabolomics, O2 and CO2 levels, bird locomotion, at the molecular, (sub)cellular, tissue, and whole organ and animal levels, can reveal important information on the properties of the underlying biological networks...
September 7, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Mario Giorgi, Stefaan W Verbruggen, Damien Lacroix
Mechanobiology, the study of the influence of mechanical loads on biological processes through signaling to cells, is fundamental to the inherent ability of bone tissue to adapt its structure in response to mechanical stimulation. The immense contribution of computational modeling to the nascent field of bone mechanobiology is indisputable, having aided in the interpretation of experimental findings and identified new avenues of inquiry. Indeed, advances in computational modeling have spurred the development of this field, shedding new light on problems ranging from the mechanical response to loading by individual cells to tissue differentiation during events such as fracture healing...
November 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
D Rose Ewald, Susan C J Sumner
Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain...
November 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Timothy Cardozo, Priyanka Gupta, Eric Ni, Lauren M Young, Doreen Tivon, Klara Felsovalyi
Molecular profiling of human diseases has been approached at the genetic (DNA), expression (RNA), and proteomic (protein) levels. An important goal of these efforts is to map observed molecular patterns to specific, mechanistic organic entities, such as loci in the genome, individual RNA molecules or defined proteins or protein assemblies. Importantly, such maps have been historically approached in the more intuitive context of a theoretical individual cell, but diseases are better described in reality using an in vivo framework, namely a library of several tissue-specific maps...
November 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Xiani Yan, Jennifer A Kruger, Xinshan Li, Poul M F Nielsen, Martyn P Nash
Vaginal delivery is the primary cause of levator ani muscle injury, which is in turn the leading factor contributing to pelvic floor disorders including pelvic organ prolapse and urinary stress incontinence. Existing biomechanical models of childbirth have provided some understanding of pelvic floor function during delivery and have helped in the investigation of preventative strategies. The modeling frameworks for childbirth simulation are described with emphasis on (1) the recent advances in medical imaging quality and computational power; (2) improvements in the anatomical representation of the pelvic floor and fetal head; (3) more realistic boundary conditions for delivery; and (4) mechanical properties determined from experiments...
November 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Graham M Donovan
Understanding lung and airway behavior presents a number of challenges, both experimental and theoretical, but the potential rewards are great in terms of both potential treatments for disease and interesting biophysical phenomena. This presents an opportunity for modeling to contribute to greater understanding, and here, we focus on modeling efforts that work toward understanding the behavior of airways in vivo, with an emphasis on asthma. We look particularly at those models that address not just isolated airways but many of the important ways in which airways are coupled both with each other and with other structures...
September 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Lina Schukur, Martin Fussenegger
Synthetic biology is a promising multidisciplinary field that brings together experts in scientific disciplines from cell biology to engineering with the goal of constructing elements that do not occur in nature for use in various applications, such as the development of novel approaches to improving healthcare management. Current disease treatment strategies are typically based on the diagnosis of phenotypic changes, which are often the result of an accumulation of endogenous metabolic defects in the human body...
September 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Rachel D Simmons, Sandeep Kumar, Salim Raid Thabet, Sanjoli Sur, Hanjoong Jo
Atherosclerosis is a multifactorial disease that preferentially occurs in arterial regions exposed to d-flow can be used to indicate disturbed flow or disturbed blood flow. The mechanisms by which d-flow induces atherosclerosis involve changes in the transcriptome, methylome, proteome, and metabolome of multiple vascular cells, especially endothelial cells. Initially, we begin with the pathogenesis of atherosclerosis and the changes that occur at multiple levels owing to d-flow, especially in the endothelium...
September 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Constantinos Siettos, Jens Starke
The extreme complexity of the brain naturally requires mathematical modeling approaches on a large variety of scales; the spectrum ranges from single neuron dynamics over the behavior of groups of neurons to neuronal network activity. Thus, the connection between the microscopic scale (single neuron activity) to macroscopic behavior (emergent behavior of the collective dynamics) and vice versa is a key to understand the brain in its complexity. In this work, we attempt a review of a wide range of approaches, ranging from the modeling of single neuron dynamics to machine learning...
September 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Jason H T Bates
Fresh air entering the mouth and nose is brought to the blood-gas barrier in the lungs by a repetitively branching network of airways. Provided the individual airway branches remain patent, this airway tree achieves an enormous amplification in cross-sectional area from the trachea to the terminal bronchioles. Obstructive lung diseases such as asthma occur when airway patency becomes compromised. Understanding the pathophysiology of these obstructive diseases thus begins with a consideration of the factors that determine the caliber of an individual airway, which include the force balance between the inward elastic recoil of the airway wall, the outward tethering forces of its parenchymal attachments, and any additional forces due to contraction of airway smooth muscle...
September 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Kwang-Hyun Cho, Jae Il Joo, Dongkwan Shin, Dongsan Kim, Sang-Min Park
Most biological processes have been considered to be irreversible for a long time, but some recent studies have shown the possibility of their reversion at a cellular level. How can we then understand the reversion of such biological processes? We introduce a unified conceptual framework based on the attractor landscape, a molecular phase portrait describing the dynamics of a molecular regulatory network, and the phenotype landscape, a map of phenotypes determined by the steady states of particular output molecules in the attractor landscape...
September 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Jonathan A Beagan, Jennifer E Phillips-Cremins
CRISPR/Cas9 genome editing studies have recently shed new light into the causal link between the linear DNA sequence and 3-D chromatin architecture. Here we describe current models for the folding of genomes into a nested hierarchy of higher-order structures and discuss new insights into the organizing principles governing genome folding at each length scale. WIREs Syst Biol Med 2016, 8:286-299. doi: 10.1002/wsbm.1338 For further resources related to this article, please visit the WIREs website.
July 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Dana-Adriana Botesteanu, Stanley Lipkowitz, Jung-Min Lee, Doron Levy
Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed...
July 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Nicoletta Castagnino, Massimo Maffei, Lorenzo Tortolina, Gabriele Zoppoli, Daniela Piras, Alessio Nencioni, Eva Moran, Alberto Ballestrero, Franco Patrone, Silvio Parodi
Current colorectal cancer (CRC) treatment guidelines are primarily based on clinical features, such as cancer stage and grade. However, outcomes may be improved using molecular treatment guidelines. Potentially useful biomarkers include driver mutations and somatically inherited alterations, signaling proteins (their expression levels and (post) translational modifications), mRNAs, micro-RNAs and long noncoding RNAs. Moving to an integrated system is potentially very relevant. To implement such an integrated system: we focus on an important region of the signaling network, immediately above the G1-S restriction point, and discuss the reconstruction of a Molecular Interaction Map and interrogating it with a dynamic mathematical model...
July 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Xin Chen, Dina Petranovic
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by accumulation of misfolded and aggregated proteins. Since the ubiquitin-proteasome system (UPS) is the major intracellular protein quality control (PQC) system in eukaryotic cells, it is likely involved in the etiology of AD. The frameshift form of ubiquitin (Ubb(+1) ) accumulates in the neuritic plaques and neurofibrillary tangles in patients with AD. Ubb(+1) accumulates in an age-dependent manner as a result of RNA-polymerase mediated molecular misreading during transcription, which allows the formation of mutant proteins in the absence of gene mutations...
July 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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