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systems biology phenotypes

William R Pitchers, Savvas J Constantinou, Mauricio Losilla, Jason R Gallant
Electric fish have served as a model system in biology since the 18th century, providing deep insight into the nature of bioelectrogenesis, the molecular structure of the synapse, and brain circuitry underlying complex behavior. Neuroethologists have collected extensive phenotypic data that span biological levels of analysis from molecules to ecosystems. This phenotypic data, together with genomic resources obtained over the past decades, have motivated new and exciting hypotheses that position the weakly electric fish model to address fundamental 21(st) century biological questions...
October 18, 2016: Journal of Physiology, Paris
James P Solomon, Brett M Lowenthal, A Karim Kader, J Kellogg Parsons, Thomas W Flaig, Arlene O Siefker-Radtke, Lars Dyrskj√łt, Donna E Hansel
Urothelial carcinoma can exhibit a wide variety of histopathological phenotypes or variant morphologies, classifications of which have recently been revised in the 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs. Many of these variants not only present diagnostic challenges, but also have clinical implications that affect patient prognosis and treatment strategies. This review will discuss these variant morphologies and their relationship to current understanding of the underlying biology of urothelial carcinoma and molecular classification paradigms...
October 18, 2016: Urology
Sayed-Rzgar Hosseini, Andreas Wagner
BACKGROUND: Biological systems are rife with examples of pre-adaptations or exaptations. They range from the molecular scale - lens crystallins, which originated from metabolic enzymes - to the macroscopic scale, such as feathers used in flying, which originally served thermal insulation or waterproofing. An important class of exaptations are novel and useful traits with non-adaptive origins. Whether such origins could be frequent cannot be answered with individual examples, because it is a question about a biological system's potential for exaptation...
October 21, 2016: BMC Systems Biology
Yang Liu, Saad M Khan, Juexin Wang, Mats Rynge, Yuanxun Zhang, Shuai Zeng, Shiyuan Chen, Joao V Maldonado Dos Santos, Babu Valliyodan, Prasad P Calyam, Nirav Merchant, Henry T Nguyen, Dong Xu, Trupti Joshi
BACKGROUND: With the advances in next-generation sequencing (NGS) technology and significant reductions in sequencing costs, it is now possible to sequence large collections of germplasm in crops for detecting genome-scale genetic variations and to apply the knowledge towards improvements in traits. To efficiently facilitate large-scale NGS resequencing data analysis of genomic variations, we have developed "PGen", an integrated and optimized workflow using the Extreme Science and Engineering Discovery Environment (XSEDE) high-performance computing (HPC) virtual system, iPlant cloud data storage resources and Pegasus workflow management system (Pegasus-WMS)...
October 6, 2016: BMC Bioinformatics
Yu Sun, Vaibhav A Narayan, Gayle M Wittenberg
BACKGROUND: Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6)...
October 21, 2016: BMC Pharmacology & Toxicology
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Fan Zhang, Min Wu, Chee Keong Kwoh, Jie Zheng
Extracellular signals are captured and transmitted by signaling proteins inside a cell. An important type of cellular responses to the signals is the cell fate decision, e.g., apoptosis. However, the underlying mechanisms of cell fate regulation are still unclear, thus comprehensive and detailed kinetic models are not yet available. Alternatively, data-driven models are promising to bridge signaling data with the phenotypic measurements of cell fates. The traditional linear model for data-driven modeling of signaling pathways has its limitations because it assumes that the a cell fate is proportional to the activities of signaling proteins, which is unlikely in the complex biological systems...
2016: PloS One
Yiwei Wang, Roberta D Brinton
Brain is the most energetically demanding organ of the body, and is thus vulnerable to even modest decline in ATP generation. Multiple neurodegenerative diseases are associated with decline in mitochondrial function, e.g., Alzheimer's, Parkinson's, multiple sclerosis and multiple neuropathies. Genetic variances in the mitochondrial genome can modify bioenergetic and respiratory phenotypes, at both the cellular and system biology levels. Mitochondrial haplotype can be a key driver of mitochondrial efficiency...
2016: Frontiers in Aging Neuroscience
Alberto Avolio
Blood vessels function as conduits for distribution of blood throughout the circulatory system. Large arteries, in addition to the essential conduit function, also serve to dampen the effect of pulsatile ventricular ejection that generates pulsatile pressure with each cardiac cycle; that is, they exhibit a 'cushion' function. The conduit function can be compromised by intimal effects that cause obstruction to flow, generally attributed to plaque formation due to intimal changes affected by atherosclerotic processes...
September 2016: Journal of Hypertension
Alberto Papi, Maria Sandra Magnoni, Carmelo Caio Muzzio, Gianmarco Benso, Andrea Rizzi
The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational multicentre international study aimed at defining COPD phenotypes and identifying biomarkers and/or genetic parameters that help to predict disease progression. The study has contributed to a better understanding of COPD heterogeneity, with the characterization of clinically important subtypes/phenotypes of patients, such as the frequent exacerbators or patient with persistent systemic inflammation, who may have different prognosis or treatment requirements...
October 14, 2016: Monaldi Archives for Chest Disease, Archivio Monaldi Per le Malattie del Torace
Bing-Ying Xie, Ai-Wen Wu
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy. METHODS: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs)...
2016: Chinese Medical Journal
B Lucendo-Villarin, H Rashidi, K Cameron, D C Hay
Pluripotent stem cell derived liver cells (hepatocytes) represent a promising alternative to primary tissue for biological and clinical applications. To date, most hepatocyte maintenance and differentiation systems have relied upon the use of animal derived components. This serves as a significant barrier to large scale production and application of stem cell derived hepatocytes. Recently, the use of defined biologics has overcome those limitations in two-dimensional monolayer culture. In order to improve the cell phenotype further, three-dimensional culture systems have been employed to better mimic the in vivo situation, drawing upon materials chemistry, engineering and biology...
May 28, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Maurizio Cirilli, Oxana Bereshchenko, Olga Ermakova, Claus Nerlov
BACKGROUND: C/EBPa and C/EBPb are transcription factors with tissue specific expression regulating several important cellular processes. They work by recruiting protein complexes to a common DNA recognition motif and both are able to compensate each other's absence in many cell types, thus showing functional redundancy. They also play distinct roles in specific cellular pathways and their abnormal functioning gives raise to different human pathologies. METHODS: To investigate the molecular basis of C/EBPa and C/EBPb specificity and redundancy we characterized their in vivo protein-protein interaction networks by Tandem Affinity Purification and Mass Spectrometry...
October 13, 2016: Biochimica et Biophysica Acta
Brigham J Hartley, Kristen J Brennand
Human induced pluripotent stem cells (hiPSCs) can theoretically yield limitless supplies of cells fated to any cell type that comprise the human organism, making them a new tool by which to potentially overcome caveats in current biomedical research. In vitro derivation of central nervous system (CNS) cell types has the potential to provide material for drug discovery and validation, safety and toxicity assays, cell replacement therapy and the elucidation of previously unknown disease mechanisms. However, current two-dimensional (2D) CNS differentiation protocols do not faithfully recapitulate the spatial organization of heterogeneous tissue, nor the cell-cell interactions, cell-extracellular matrix interactions, or specific physiological functions generated within complex tissue such as the brain...
October 12, 2016: Neurochemistry International
Tsuyoshi Momose, Jean-Paul Concordet
More and more genomes are sequenced and a great range of biological questions can be examined at the genomic level in a growing number of organisms. Testing the function of genome features, from gene networks, genome organization, conserved non-coding sequences to microRNAs, and, more generally, experimentally addressing the genotype-phenotype relationship is now possible owing to the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 revolution of genome editing. In the present review, we give a brief overview of the CRISPR/Cas9 toolbox and different strategies for genome editing currently available...
October 11, 2016: Marine Genomics
Jose Negrete, Alain Pumir, Hsin-Fang Hsu, Christian Westendorf, Marco Tarantola, Carsten Beta, Eberhard Bodenschatz
Biological systems with their complex biochemical networks are known to be intrinsically noisy. Here we investigate the dynamics of actin polymerization of amoeboid cells, which are close to the onset of oscillations. We show that the large phenotypic variability in the polymerization dynamics can be accurately captured by a generic nonlinear oscillator model in the presence of noise. We determine the relative role of the noise with a single dimensionless, experimentally accessible parameter, thus providing a quantitative description of the variability in a population of cells...
September 30, 2016: Physical Review Letters
Jeffrey K Wickliffe, Stephen D Dertinger, Dorothea K Torous, Svetlana L Avlasevich, Bridget R Simon-Friedt, Mark J Wilson
Obesity increases the risk of a number of chronic diseases in humans including several cancers. Biological mechanisms responsible for such increased risks are not well understood at present. Increases in systemic inflammation and oxidative stress, endogenous production of mutagenic metabolites, altered signaling in proliferative pathways, and increased sensitivity to exogenous mutagens and carcinogens are some of the potential contributing factors. We hypothesize that obesity creates an endogenously mutagenic environment in addition to increasing the sensitivity to environmental mutagens...
October 14, 2016: Environmental and Molecular Mutagenesis
Paul Macklin, Hermann B Frieboes, Jessica L Sparks, Ahmadreza Ghaffarizadeh, Samuel H Friedman, Edwin F Juarez, Edmond Jonckheere, Shannon M Mumenthaler
Tumors cannot be understood in isolation from their microenvironment. Tumor and stromal cells change phenotype based upon biochemical and biophysical inputs from their surroundings, even as they interact with and remodel the microenvironment. Cancer should be investigated as an adaptive, multicellular system in a dynamical microenvironment. Computational modeling offers the potential to detangle this complex system, but the modeling platform must ideally account for tumor heterogeneity, substrate and signaling factor biotransport, cell and tissue biophysics, tissue and vascular remodeling, microvascular and interstitial flow, and links between all these sub-systems...
2016: Advances in Experimental Medicine and Biology
Stephen P Dzul, Agostinho G Rocha, Swati Rawat, Ashoka Kandegedara, April Kusowski, Jayashree Pain, Anjaneyulu Murari, Debkumar Pain, Andrew Dancis, Timothy L Stemmler
FeS-clusters are utilized by numerous proteins within several biological pathways that are essential for life. In eukaryotes, the primary FeS-cluster production pathway is the mitochondrial iron-sulfur cluster (ISC) pathway. In Saccharomyces cerevisiae, de novo FeS-cluster formation is accomplished through coordinated assembly with the substrates iron and sulfur by the scaffold assembly protein "Isu1". Sulfur for cluster assembly is provided by cysteine desulfurase "Nfs1", a protein that works in union with its accessory protein "Isd11"...
October 14, 2016: Metallomics: Integrated Biometal Science
Aida Moreno-Moral, Enrico Petretto
Complementary to traditional gene mapping approaches used to identify the hereditary components of complex diseases, integrative genomics and systems genetics have emerged as powerful strategies to decipher the key genetic drivers of molecular pathways that underlie disease. Broadly speaking, integrative genomics aims to link cellular-level traits (such as mRNA expression) to the genome to identify their genetic determinants. With the characterization of several cellular-level traits within the same system, the integrative genomics approach evolved into a more comprehensive study design, called systems genetics, which aims to unravel the complex biological networks and pathways involved in disease, and in turn map their genetic control points...
October 1, 2016: Disease Models & Mechanisms
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