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https://www.readbyqxmd.com/read/28231035/biologically-relevant-heterogeneity-metrics-and-practical-insights
#1
Albert Gough, Andrew M Stern, John Maier, Timothy Lezon, Tong-Ying Shun, Chakra Chennubhotla, Mark E Schurdak, Steven A Haney, D Lansing Taylor
Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in a wide range of biomedical applications, including basic biomedical research, drug discovery, diagnostics, and the implementation of precision medicine. There are a number of published approaches to characterizing heterogeneity in cells in vitro and in tissue sections. However, there are no generally accepted approaches for the detection and quantitation of heterogeneity that can be applied in a relatively high-throughput workflow...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28230815/conceptual-foundations-of-systems-biology-explaining-complex-cardiac-diseases
#2
REVIEW
George E Louridas, Katerina G Lourida
Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine...
February 21, 2017: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/28228756/agonistic-anti-pdgf-receptor-autoantibodies-from-patients-with-systemic-sclerosis-impact-human-pulmonary-artery-smooth-muscle-cells-function-in-vitro
#3
Silvia Svegliati, Donatella Amico, Tatiana Spadoni, Colomba Fischetti, Doreen Finke, Gianluca Moroncini, Chiara Paolini, Cecilia Tonnini, Antonella Grieco, Marina Rovinelli, Armando Gabrielli
One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228536/a-viral-satellite-dna-vector-tylccnv-for-functional-analysis-of-mirnas-and-sirnas-in-plants
#4
Zheng Ju, Dongyan Cao, Chao Gao, Jinhua Zuo, Baiqiang Zhai, Shan Li, Hongliang Zhu, Daqi Fu, Yunbo Luo, Benzhong Zhu
With experimental and bioinformatical methods, numerous small RNAs, including microRNAs (miRNAs) and short interfering RNAs (siRNAs), have been found in plants, and they play vital roles in various biological regulation processes. However, most of these small RNAs remain to be functionally characterized. Until now, only several viral vectors were developed to overexpress miRNAs with limited application in plants. In this study, we reported a new small RNAs overexpression system via viral satellite DNA associated with Tomato yellow leaf curl China virus (TYLCCNV) vector, which could highly overexpress not only artificial and endogenous miRNAs but also endogenous siRNAs in Nicotiana benthamiana...
February 22, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28226701/an-image-resolution-perspective-on-functional-activity-mapping
#5
Keith Dillon, Yu-Ping Wang, Keith Dillon, Yu-Ping Wang, Yu-Ping Wang, Keith Dillon
In this paper we apply techniques for numerical estimation of system resolution from imaging, to the regression problem of relating biological data to phenotypes. Our approach can be viewed as an extension of Backus-Gilbert theory, which attempts to find the most concentrated estimator that may be reliably computed in an inverse problem. Applied to a regression model, we estimate a minimal combination of collinear variables that may be found in a predictor, which gives a robust multivariable estimate of the network relationships in the data...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226226/microglia-function-in-the-central-nervous-system-during-health-and-neurodegeneration
#6
Marco Colonna, Oleg Butovsky
Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses...
February 9, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#7
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28223180/biomechanical-aspects-of-axonal-damage-in-glaucoma-a-brief-review
#8
REVIEW
Cheri Stowell, Claude Burgoyne, Ernst R Tamm, C Ross Ethier
The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans...
February 18, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28220428/network-reconstitution-for-quantitative-subnetwork-interaction-analysis
#9
Fumiaki Katagiri
A fundamental task in systems biology is to quantify the contributions of the systems' parts and their interactions. Here I describe a powerful concept and tool for this purpose: network reconstitution. Genotypes of an organism that represent all possible combinations of the subnetworks in question will be quantitatively phenotyped. The quantitative phenotype data is analyzed using an R script to obtain estimates for single subnetwork contributions and their interactions.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220109/temporal-stability-and-the-effect-of-transgenerational-transfer-on-fecal-microbiota-structure-in-a-long-distance-migratory-bird
#10
Jakub Kreisinger, Lucie Kropáčková, Adéla Petrželková, Marie Adámková, Oldřich Tomášek, Jean-François Martin, Romana Michálková, Tomáš Albrecht
Animal bodies are inhabited by a taxonomically and functionally diverse community of symbiotic and commensal microorganisms. From an ecological and evolutionary perspective, inter-individual variation in host-associated microbiota contributes to physiological and immune system variation. As such, host-associated microbiota may be considered an integral part of the host's phenotype, serving as a substrate for natural selection. This assumes that host-associated microbiota exhibits high temporal stability, however, and that its composition is shaped by trans-generational transfer or heritable host-associated microbiota modulators encoded by the host genome...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28217849/how-long-bones-grow-children-mechanistic-paths-to-variation-in-human-height-growth
#11
REVIEW
Michelle Lampl, Meriah Schoen
OBJECTIVES: Eveleth and Tanner's descriptive documentation of worldwide variability in human growth provided evidence of the interaction between genetics and environment during development that has been foundational to the science of human growth. There remains a need, however, to describe the mechanistic foundations of variability in human height growth patterns. METHODS: A review of research documenting cellular activities at the endochondral growth plate aims to show how the unique microenvironment and cell functions during the sequential phases of the chondrocyte lifecycle affect long bone elongation, a fundamental source of height growth...
February 20, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28216262/efis-lecture-understanding-the-ctla-4-checkpoint-in-the-maintenance-of-immune-homeostasis
#12
REVIEW
Lucy S K Walker
The past 20 years have heralded fascinating developments in the field of CTLA-4 biology. The CTLA-4 protein is a critical negative regulator of T cell immunity and its absence provokes severe lymphoproliferative disease. In a surprising twist, the generation of mixed bone marrow chimeric mice revealed that CTLA-4 predominantly functions in a cell-extrinsic manner, suggesting that CTLA-4 expressed on one cell can modify the behaviour of another cell. This was followed by the demonstration that CTLA-4 is highly expressed in regulatory T cells and can contribute to their suppressive activity...
February 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28213964/when-sensing-is-gambling-an-experimental-system-reveals-how-plasticity-can-generate-tunable-bet-hedging-strategies
#13
Colin S Maxwell, Paul M Magwene
Genotypes can persist in unpredictable environments by 'hedging their bets' and producing diverse phenotypes. Theoretical studies have shown that the phenotypic variability needed for a bet-hedging strategy can be generated by factors either inside or outside an organism. However, sensing the environment and bet hedging are frequently treated as distinct evolutionary strategies. Furthermore, nearly all empirical studies of the molecular underpinnings of bet-hedging strategies to date have focused on internal sources of variability...
February 18, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28213165/hbvcircle-a-novel-tool-to-investigate-hepatitis-b-virus-covalently-closed-circular-dna
#14
Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A T Young, Lu Gao
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E...
February 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28212725/lipid-peroxidation-in-cell-death
#15
REVIEW
Michael M Gaschler, Brent R Stockwell
Disruption of redox homeostasis is a key phenotype of many pathological conditions. Though multiple oxidizing compounds such as hydrogen peroxide are widely recognized as mediators and inducers of oxidative stress, increasingly, attention is focused on the role of lipid hydroperoxides as critical mediators of death and disease. As the main component of cellular membranes, lipids have an indispensible role in maintaining the structural integrity of cells. Excessive oxidation of lipids alters the physical properties of cellular membranes and can cause covalent modification of proteins and nucleic acids...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212541/analysis-of-variability-in-high-throughput-screening-data-applications-to-melanoma-cell-lines-and-drug-responses
#16
Kuan-Fu Ding, Darren Finlay, Hongwei Yin, William P D Hendricks, Chris Sereduk, Jeffrey Kiefer, Aleksandar Sekulic, Patricia M LoRusso, Kristiina Vuori, Jeffrey M Trent, Nicholas J Schork
High-throughput screening (HTS) strategies and protocols have undergone significant development in the last decade. It is now possible to screen hundreds of thousands of compounds, each exploring multiple biological phenotypes and parameters, against various cell lines or model systems in a single setting. However, given the vast amount of data such studies generate, the fact that they use multiple reagents, and are often technician-intensive, questions have been raised about the variability, reliability and reproducibility of HTS results...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212522/taking-up-the-cudgels-for-the-traditional-reactive-oxygen-and-nitrogen-species-detection-assays-and-their-use-in-the-cardiovascular-system
#17
REVIEW
Andreas Daiber, Matthias Oelze, Sebastian Steven, Swenja Kröller-Schön, Thomas Münzel
Reactive oxygen and nitrogen species (RONS such as H2O2, nitric oxide) confer redox regulation of essential cellular functions (e.g. differentiation, proliferation, migration, apoptosis), initiate and catalyze adaptive stress responses. In contrast, excessive formation of RONS caused by impaired break-down by cellular antioxidant systems and/or insufficient repair of the resulting oxidative damage of biomolecules may lead to appreciable impairment of cellular function and in the worst case to cell death, organ dysfunction and severe disease phenotypes of the entire organism...
February 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212112/cancer-as-robust-intrinsic-state-shaped-by-evolution-a-key-issues-review
#18
Ruoshi Yuan, Xiaomei Zhu, Gaowei Wang, Site Li, Ping Ao
Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players-genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large 'omics' data also require a new mechanistic and global underpinning to organize for rationalizing cancer complexity. A unifying and quantitative theory was proposed by some of the present authors that cancer is a robust state formed by the endogenous molecular-cellular network, which is evolutionarily built for the developmental processes and physiological functions...
February 17, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28207813/interacting-networks-of-resistance-virulence-and-core-machinery-genes-identified-by-genome-wide-epistasis-analysis
#19
Marcin J Skwark, Nicholas J Croucher, Santeri Puranen, Claire Chewapreecha, Maiju Pesonen, Ying Ying Xu, Paul Turner, Simon R Harris, Stephen B Beres, James M Musser, Julian Parkhill, Stephen D Bentley, Erik Aurell, Jukka Corander
Recent advances in the scale and diversity of population genomic datasets for bacteria now provide the potential for genome-wide patterns of co-evolution to be studied at the resolution of individual bases. Here we describe a new statistical method, genomeDCA, which uses recent advances in computational structural biology to identify the polymorphic loci under the strongest co-evolutionary pressures. We apply genomeDCA to two large population data sets representing the major human pathogens Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A Streptococcus)...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28203244/pistil-transcriptome-analysis-to-disclose-genes-and-gene-products-related-to-aposporous-apomixis-in-hypericum-perforatum-l
#20
Giulio Galla, Sara Zenoni, Linda Avesani, Lothar Altschmied, Paride Rizzo, Timothy F Sharbel, Gianni Barcaccia
Unlike sexual reproduction, apomixis encompasses a number of reproductive strategies, which permit maternal genome inheritance without genetic recombination and syngamy. The key biological features of apomixis are the circumvention of meiosis (i.e., apomeiosis), the differentiation of unreduced embryo sacs and egg cells, and their autonomous development in functional embryos through parthenogenesis, and the formation of viable endosperm either via fertilization-independent means or following fertilization with a sperm cell...
2017: Frontiers in Plant Science
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