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Modeling gene regulation

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https://www.readbyqxmd.com/read/28651020/the-nervous-system-of-the-adult-ascidian-ciona-intestinalis-type-a-ciona-robusta-insights-from-transgenic-animal-models
#1
Tomohiro Osugi, Yasunori Sasakura, Honoo Satake
The nervous system of ascidians is an excellent model system to provide insights into the evolutionary process of the chordate nervous system due to their phylogenetic positions as the sister group of vertebrates. However, the entire nervous system of adult ascidians has yet to be functionally and anatomically investigated. In this study, we have revealed the whole dorsal and siphon nervous system of the transgenic adult ascidian of Ciona intestinalis Type A (Ciona robusta) in which a Kaede reporter gene is expressed in a pan-neuronal fashion...
2017: PloS One
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#2
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650102/endocrine-influence-on-neuroinflammation-the-use-of-reporter-systems
#3
REVIEW
Nicoletta Rizzi, Alessandro Villa, Valeria Benedusi, Electra Brunialti, Nicoletta Cesari, Paolo Ciana, Adriana Maggi
Most of the ageing-associated pathologies are coupled with a strong inflammatory component that accelerates the progress of the physio-pathological functional decline related to ageing. The currently available pharmacological tools for the control of neuroinflammation present several side effects which restrict their application, particularly in chronic disorders. The discovery of the potential anti-inflammatory action exerted by endogenous estrogens and that activation of ERα results in a significant decrease of inflammation at the cellular level and in models of inflammatory diseases, prompted us to embark in a series of studies aimed at the generation of reporter systems allowing to i...
June 26, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28650069/transcriptional-engineering-of-the-glyceraldehyde-3-phosphate-dehydrogenase-promoter-for-improved-heterologous-protein-production-in-pichia-pastoris
#4
Özge Ata, Roland Prielhofer, Brigitte Gasser, Diethard Mattanovich, Pınar Çalık
The constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP ), which is one of the benchmark promoters of Pichia pastoris, was analyzed in terms of putative transcription factor binding sites. We constructed a synthetic library with distinct regulatory properties through deletion and duplication of these putative transcription factor binding sites and selected transcription factor (TF) genes were overexpressed or deleted to understand their roles on heterologous protein production. Using enhanced green fluorescent protein, an expression strength in a range between 0...
June 26, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28649443/a-multiscale-model-of-early-cell-lineage-specification-including-cell-division
#5
Alen Tosenberger, Didier Gonze, Sylvain Bessonnard, Michel Cohen-Tannoudji, Claire Chazaud, Geneviève Dupont
Embryonic development is a self-organised process during which cells divide, interact, change fate according to a complex gene regulatory network and organise themselves in a three-dimensional space. Here, we model this complex dynamic phenomenon in the context of the acquisition of epiblast and primitive endoderm identities within the inner cell mass of the preimplantation embryo in the mouse. The multiscale model describes cell division and interactions between cells, as well as biochemical reactions inside each individual cell and in the extracellular matrix...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28649434/a-clb-cdk1-mediated-regulation-of-fkh2-synchronizes-clb-expression-in-the-budding-yeast-cell-cycle
#6
Christian Linke, Anastasia Chasapi, Alberto González-Novo, Istabrak Al Sawad, Silvia Tognetti, Edda Klipp, Mart Loog, Sylvia Krobitsch, Francesc Posas, Ioannis Xenarios, Matteo Barberis
Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28649368/wnt-target-genes-and-where-to-find-them
#7
REVIEW
Aravinda-Bharathi Ramakrishnan, Ken M Cadigan
Wnt/β-catenin signaling is highly conserved throughout metazoans, is required for numerous essential events in development, and serves as a stem cell niche signal in many contexts. Misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt stimulation results in stabilization and nuclear import of β-catenin, which then acts as a transcriptional co-activator. Transcription factors of the T-cell family (TCF) are the best-characterized nuclear binding partners of β-catenin and mediators of Wnt gene regulation...
2017: F1000Research
https://www.readbyqxmd.com/read/28649363/genetic-and-epigenetic-control-of-gene-expression-by-crispr-cas-systems
#8
REVIEW
Albert Lo, Lei Qi
The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems has revolutionized the way researchers edit genomes. Engineering of catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas]) combined with transcriptional repressors, activators, or epigenetic modifiers enable sequence-specific regulation of gene expression and chromatin state. These CRISPR-Cas-based technologies have contributed to the rapid development of disease models and functional genomics screening approaches, which can facilitate genetic target identification and drug discovery...
2017: F1000Research
https://www.readbyqxmd.com/read/28648749/transcriptome-profiling-of-3d-co-cultured-cardiomyocytes-and-endothelial-cells-under-oxidative-stress-using-a-photocrosslinkable-hydrogel-system
#9
Xiaoshan Yue, Aylin Acun, Pinar Zorlutuna
Myocardial infarction (MI) is one of the most common among cardiovascular diseases. Endothelial cells (ECs) are considered to have protective effects on cardiomyocytes (CMs) under stress conditions such as MI; however, the paracrine CM-EC crosstalk and the resulting endogenous cellular responses that could contribute to this protective effect are not thoroughly investigated. Here we created biomimetic synthetic tissues containing CMs and human induced pluripotent stem cell (hiPSC)-derived ECs (iECs), which showed improved cell survival compared to single cultures under conditions mimicking the aftermath of MI, and performed high-throughput RNA-sequencing to identify target pathways that could govern CM-iEC crosstalk and the resulting improvement in cell viability...
June 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28648582/molecular-mechanism-of-phosphate-signaling-in-plants
#10
REVIEW
Fei Wang, Meiju Deng, Jiming Xu, Xinlu Zhu, Chuanzao Mao
Phosphorus (P) is one of the indispensable macronutrients for plant growth and development. To adapt to low phosphate (Pi) environment, plants have evolved complex responsive and adaptive mechanisms for acquisition and remobilization of phosphate to maintain P homeostasis, which are regulated by complex gene regulation networks through the functions of Pi transporters (PTs) and other Pi starvation induced (PSI) genes. This review summarizes the recent progresses on the molecular regulation mechanism of phosphate transporters and phosphate signal transduction pathway (also called phosphate signaling) in dicot model plant Arabidopsis (Arabidopsis thaliana) and monocot model plant rice (Oryza sativa L...
June 22, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28648455/kinetic-modelling-and-meta-analysis-of-the-b-subtilis-siga-regulatory-network-during-spore-germination-and-outgrowth
#11
O Ramaniuk, M Černý, L Krásný, J Vohradsky
This study describes the meta-analysis and kinetic modelling of gene expression control by sigma factor SigA of Bacillus subtilis during germination and outgrowth based on microarray data from 14 time points. The analysis computationally models the direct interaction among SigA, SigA-controlled sigma factor genes (sigM, sigH, sigD, sigX), and their target genes. Of the >800 known genes in the SigA regulon, as extracted from databases, 311 genes were analysed, and 190 were confirmed by the kinetic model as being controlled by SigA...
June 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28647924/comparative-expression-analysis-of-rice-and-arabidopsis-peroxiredoxin-genes-suggests-conserved-or-diversified-roles-between-the-two-species-and-leads-to-the-identification-of-tandemly-duplicated-rice-peroxiredoxin-genes-differentially-expressed-in-seeds
#12
Yun-Shil Gho, Sun-A Park, Sung-Ruyl Kim, Anil Kumar Nalini Chandran, Gynheung An, Ki-Hong Jung
BACKGROUND: Peroxiredoxins (PRXs) have recently been identified as plant antioxidants. Completion of various genome sequencing projects has provided genome-wide information about PRX genes in major plant species. Two of these -- Oryza sativa (rice) and Arabidopsis -- each have 10 PRX members. Although significant progress has been made in understanding their biological roles in Arabidopsis, those functions in rice, a model crop plant, have not been well studied. RESULTS: We performed a comparative expression analysis of rice and Arabidopsis PRXs...
December 2017: Rice
https://www.readbyqxmd.com/read/28647646/the-secreted-protein-wnt5a-regulates-condylar-chondrocyte-proliferation-hypertrophy-and-migration
#13
Xianpeng Ge, Ruirui Shi, Xuchen Ma
OBJECTIVE: Our previous study showed that WNT5A, a member of the noncanonical WNT pathway, is involved in interleukin-1beta induced matrix metalloproteinase expression in temporomandibular joint (TMJ) condylar chondrocytes. The purpose of this study is to further explore the roles of WNT5A in cartilage biology of the TMJ. METHODS: An early TMJ osteoarthritis-like rat model was constructed by a mechanical method (steady mouth-opening). The gene and protein levels of WNT5A during the condylar cartilage changes were measured...
June 16, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28647579/frailty-is-associated-with-lower-expression-of-genes-involved-in-cellular-response-to-stress-results-from-the-toledo-study-for-healthy-aging
#14
Mariam El Assar, Javier Angulo, José Antonio Carnicero, Stefan Walter, Francisco José García-García, Eva López-Hernández, José-María Sánchez-Puelles, Leocadio Rodríguez-Mañas
BACKGROUND: Specific mechanisms underlying frailty syndrome are not well known. Frailty can be viewed as a loss of functional reserve resulting in increased vulnerability to stressors. We hypothesize that pathways regulating cellular response to stress are potential players in the development of frailty. The aim of this study was to evaluate the association of the expression of certain genes related to cellular response to stress with the presence of frailty in older patients. METHODS: A sample of 350 individuals aged 65 years or older (22% frail) was selected from the Toledo Study of Healthy Aging...
June 21, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#15
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647555/normalizing-the-gene-dosage-of-dyrk1a-in-a-mouse-model-of-down-syndrome-rescues-several-alzheimer-s-disease-phenotypes
#16
Susana García-Cerro, Noemí Rueda, Verónica Vidal, Sara Lantigua, Carmen Martínez-Cué
The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer's disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology...
June 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#17
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28647356/optimizing-bone-morphogenic-protein-4-mediated-human-embryonic-stem-cell-differentiation-into-trophoblast-like-cells-using-fibroblast-growth-factor-2-and-transforming-growth-factor-%C3%AE-activin-nodal-signalling-inhibition
#18
Mariann Koel, Urmo Võsa, Kaarel Krjutškov, Elisabet Einarsdottir, Juha Kere, Juha Tapanainen, Shintaro Katayama, Sulev Ingerpuu, Viljar Jaks, Ulf-Hakan Stenman, Karolina Lundin, Timo Tuuri, Andres Salumets
Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days...
June 12, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28646471/decoding-early-myelopoiesis-from-dynamics-of-core-endogenous-network
#19
Hang Su, Gaowei Wang, Ruoshi Yuan, Junqiang Wang, Ying Tang, Ping Ao, Xiaomei Zhu
A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network perspective. Indeed, there are numerical difficulties even for those who were determined to explore along this direction. Undeterred, seven years ago a group of Chinese scientists started a program aiming to obtain quantitative connections between tumors and network dynamics. Many interesting results have been obtained...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28646459/silymarin-inhibits-adipogenesis-in-the-adipocytes-in-grass-carp-ctenopharyngodon-idellus-in-vitro-and-in-vivo
#20
Peizhen Xiao, Zhou Yang, Jian Sun, Jingjing Tian, Zhiguang Chang, Xuexian Li, Baotong Zhang, Yuantu Ye, Hong Ji, Ermeng Yu, Jun Xie
In this study, two experiments were performed to explore the function of silymarin in adipogenesis in grass carp (Ctenopharyngodon idellus) using in vitro and in vivo models. In experiment 1, differentiated grass carp pre-adipocytes were treated with silymarin for 6 days. Treatment with 100 μg mL(-1)silymarin (SM100 group) significantly reduced triglyceride accumulation at day 6. The adipogenic gene expression levels of PPARγ, C/EBPα, SREBP1c, FAS, SCD1, and LPL, and the protein expression level of PPARγ were significantly down-regulated in the SM100 group...
June 23, 2017: Fish Physiology and Biochemistry
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