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Modelling somatic growth

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https://www.readbyqxmd.com/read/29151865/effect-of-cell-cycle-duration-on-somatic-evolutionary-dynamics
#1
Dominik Wodarz, Ajay Goel, Natalia L Komarova
Cellular checkpoints prevent damage and mutation accumulation in tissue cells. DNA repair is one mechanism that can be triggered by checkpoints and involves temporary cell cycle arrest and thus delayed reproduction. Repair-deficient cells avoid this delay, which has been argued to lead to a selective advantage in the presence of frequent damage. We investigate this hypothesis with stochastic modeling, using mathematical analysis and agent-based computations. We first model competition between two cell types: a cell population that enters temporary cell cycle arrest, corresponding to repair (referred to as arresting cells), and one that does not enter arrest (referred to as nonarresting cells)...
December 2017: Evolutionary Applications
https://www.readbyqxmd.com/read/29145629/the-reactome-pathway-knowledgebase
#2
Antonio Fabregat, Steven Jupe, Lisa Matthews, Konstantinos Sidiropoulos, Marc Gillespie, Phani Garapati, Robin Haw, Bijay Jassal, Florian Korninger, Bruce May, Marija Milacic, Corina Duenas Roca, Karen Rothfels, Cristoffer Sevilla, Veronica Shamovsky, Solomon Shorser, Thawfeek Varusai, Guilherme Viteri, Joel Weiser, Guanming Wu, Lincoln Stein, Henning Hermjakob, Peter D'Eustachio
The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism, and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression profiles or somatic mutation catalogues from tumor cells...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29131079/are-inflammatory-cytokines-associated-with-pain-during-acute-myocardial-infarction
#3
Laurin Imholz, Rebecca E Meister-Langraf, Mary Princip, Michaela Fux, Ulrich Schnyder, Jürgen Barth, Hansjörg Znoj, Jean-Paul Schmid, Roland von Känel
OBJECTIVE: Pain and inflammation during acute myocardial infarction (AMI) have been associated with the development of posttraumatic stress disorder and may also impact negatively on somatic outcome. We investigated the relationship between pain during AMI and levels of circulating proinflammatory (tumor necrosis factor [TNF]-α, interleukin [IL]-6) and anti-inflammatory (IL-33 and tissue growth factor [TGF]-β1) cytokines. METHODS: Data were collected as part of the Myocardial Infarction - Stress Prevention Intervention (MI-SPRINT) study...
November 4, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29107533/h3-3-k27m-cooperates-with-trp53-loss-and-pdgfra-gain-in-mouse-embryonic-neural-progenitor-cells-to-induce-invasive-high-grade-gliomas
#4
Manav Pathania, Nicolas De Jay, Nicola Maestro, Ashot S Harutyunyan, Justyna Nitarska, Pirasteh Pahlavan, Stephen Henderson, Leonie G Mikael, Angela Richard-Londt, Ying Zhang, Joana R Costa, Steven Hébert, Sima Khazaei, Nisreen Samir Ibrahim, Javier Herrero, Antonella Riccio, Steffen Albrecht, Robin Ketteler, Sebastian Brandner, Claudia L Kleinman, Nada Jabado, Paolo Salomoni
Gain-of-function mutations in histone 3 (H3) variants are found in a substantial proportion of pediatric high-grade gliomas (pHGG), often in association with TP53 loss and platelet-derived growth factor receptor alpha (PDGFRA) amplification. Here, we describe a somatic mouse model wherein H3.3(K27M) and Trp53 loss alone are sufficient for neoplastic transformation if introduced in utero. H3.3(K27M)-driven lesions are clonal, H3K27me3 depleted, Olig2 positive, highly proliferative, and diffusely spreading, thus recapitulating hallmark molecular and histopathological features of pHGG...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29093017/a-population-of-heterogeneous-breast-cancer-patient-derived-xenografts-demonstrate-broad-activity-of-parp-inhibitor-in-brca1-2-wild-type-tumors
#5
Kurt W Evans, Erkan Yuca, Argun Akcakanat, Stephen M Scott, Natalia Paez Arango, Xiaofeng Zheng, Ken Chen, Coya Tapia, Emily Tarco, Agda K Eterovic, Dalliah M Black, Jennifer K Litton, Timothy A Yap, Debu Tripathy, Gordon B Mills, Funda Meric-Bernstam
Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29069360/mouse-models-of-primary-aldosteronism-from-physiology-to-pathophysiology
#6
Leticia Aragao-Santiago, Celso E Gomez-Sanchez, Paolo Mulatero, Ariadni Spyroglou, Martin Reincke, Tracy Ann Williams
Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown...
October 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/29068043/life-history-strategies-of-the-rock-hind-grouper-epinephelus-adscensionis-at-ascension-island
#7
E T Nolan, K J Downes, A Richardson, A Arkhipkin, P Brickle, J Brown, R J Mrowicki, Z Shcherbich, N Weber, S B Weber
Epinephelus adscensionis sampled from Ascension Island, South Atlantic Ocean, exhibits distinct life-history traits, including larger maximum size and size at sexual maturity than previous studies have demonstrated for this species in other locations. Otolith analysis yielded a maximum estimated age of 25 years, with calculated von Bertalanffy growth parameters of: L∞  = 55·14, K = 0·19, t0  = -0·88. Monthly gonad staging and analysis of gonad-somatic index (IG ) provide evidence for spawning from July to November with an IG peak in August (austral winter), during which time somatic growth is also suppressed...
October 25, 2017: Journal of Fish Biology
https://www.readbyqxmd.com/read/29061671/meiosis-like-functions-in-oncogenesis-a-new-view-of-cancer
#8
Ramsay J McFarlane, Jane A Wakeman
Cancer cells have many abnormal characteristics enabling tumors to grow, spread, and avoid immunologic and therapeutic destruction. Central to this is the innate ability of populations of cancer cells to rapidly evolve. One feature of many cancers is that they activate genes that are normally associated with distinct developmental states, including germ cell-specific genes. This has historically led to the proposal that tumors take on embryonal characteristics, the so called embryonal theory of cancer. However, one group of germline genes, not directly associated with embryonic somatic tissue genesis, is the one that encodes the specific factors to drive the unique reductional chromosome segregation of meiosis I, which also results in chromosomal exchanges...
October 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/29037382/influences-of-dietary-lipid-and-temperature-on-growth-fat-deposition-and-lipoprotein-lipase-expression-in-darkbarbel-catfish-pelteobagrus-vachellii
#9
Jun Qiang, Yi-Fan Tao, Jie He, Jin-Wen Bao, Hong-Xia Li, Wen-Bo Shi, Pao Xu, Yi-Lan Sun
Darkbarbel catfish (Pelteobagrus vachellii) is an important freshwater fish in China. Water temperature greatly influences the absorption and utilization of dietary lipid by fish. Response values (including growth, hepatic fat deposition, and gene expression) for darkbarbel catfish mediated by two factors (water temperature 20-34°C; dietary lipid level 2-17%) were the focus of this study. The relationship between the two factors and the response values was evaluated by the response surface method using the central composite design...
October 2017: Journal of Thermal Biology
https://www.readbyqxmd.com/read/29029246/the-epidermal-growth-factor-network-role-in-oocyte-growth-maturation-and-developmental-competence
#10
Dulama Richani, Robert B Gilchrist
BACKGROUND: The LH surge induces great physiological changes within the preovulatory follicle, which culminate in the ovulation of a mature oocyte that is capable of supporting embryo and foetal development. However, unlike mural granulosa cells, the oocyte and its surrounding cumulus cells are not directly responsive to LH, indicating that the LH signal is mediated by secondary factors produced by the granulosa cells. The mechanisms by which the oocyte senses the ovulatory LH signal and hence prepares for ovulation has been a subject of considerable controversy for the past four decades...
September 20, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29029116/upregulation-of-irs1-enhances-igf1-response-in-y537s-and-d538g-esr1-mutant-breast-cancer-cells
#11
Zheqi Li, Kevin M Levine, Amir Bahreini, Peilu Wang, David Chu, Ben Ho Park, Steffi Oesterreich, Adrian V Lee
Increased evidence suggests that somatic mutations in the ligand binding domain of estrogen receptor (ERα/ESR1) are critical mediators of endocrine-resistant breast cancer progression. Insulin-like growth factor-1 (IGF1) is an essential regulator of breast development and tumorigenesis, and also has a role in endocrine resistance. A recent study showed enhanced crosstalk between IGF1 and ERα in ESR1 mutant cells, but detailed mechanisms are incompletely understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and D538G ESR1 mutations, we characterized altered IGF1 signaling...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28982680/chronic-psychosocial-stress-disturbs-long-bone-growth-in-adolescent-mice
#12
S Foertsch, M Haffner-Luntzer, J Kroner, F Gross, K Kaiser, M Erber, S O Reber, A Ignatius
Although a strong association between psychiatric and somatic disorders is generally accepted, little is known regarding the interrelation between mental and skeletal health. While depressive disorders were shown to be strongly associated with osteoporosis and increased fracture risk, evidence from post-traumatic stress disorder (PTSD) patients is less consistent. Therefore, the present study investigated the influence of chronic psychosocial stress on bone using a well-established murine model for PTSD. 7-week-old C57BL/6N mice were subjected to chronic subordinate colony housing (CSC) for 19 days, whereas control mice were singly housed...
October 5, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28980053/serial-versus-direct-dilation-of-small-diameter-stents-results-in-a-more-predictable-and-complete-intentional-transcatheter-stent-fracture-a-pices-bench-testing-study
#13
Matthew A Crystal, Gareth J Morgan, Saar Danon, Robert G Gray, Daniel H Gruenstein, Brent M Gordon, Bryan H Goldstein
Balloon-expandable stents, implanted in infants and children with congenital heart disease (CHD), often require redilation to match somatic growth. Small diameter stents may eventually require longitudinal surgical transection to prevent iatrogenic vascular stenosis. Intentional transcatheter stent fracture (TSF) is an emerging alternative approach to stent transection, but little is known about the optimal stent substrate and best protocol to improve the likelihood of successful TSF. Bench testing was performed with a stent dilation protocol...
October 4, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28945226/pten-deficiency-sensitizes-endometrioid-endometrial-cancer-to-compound-parp-pi3k-inhibition-but-not-parp-inhibition-as-monotherapy
#14
X Bian, J Gao, F Luo, C Rui, T Zheng, D Wang, Y Wang, T M Roberts, P Liu, J J Zhao, H Cheng
Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising cancer therapeutics especially for tumors with deficient homologous recombination (HR) repair. However, as HR-deficient tumors represent only a small fraction of endometrial cancers, the therapeutic utility of PARP inhibitors is limited in this disease. Somatic loss of phosphatase and tensin homolog (PTEN), a tumor suppressor that counteracts phosphoinositide 3-kinase (PI3K) activity, is one of the most common genetic aberrations in endometrioid endometrial cancer...
September 25, 2017: Oncogene
https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#15
Margit Rosner, Ha Thi Thanh Pham, Richard Moriggl, Markus Hengstschläger
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927462/generation-of-special-autosomal-dominant-polycystic-kidney-disease-ipscs-with-the-capability-of-functional-kidney-like-cell-differentiation
#16
Jiahui Huang, Shumin Zhou, Xin Niu, Bin Hu, Qing Li, Feng Zhang, Xue Zhang, Xiujuan Cai, Yuanlei Lou, Fen Liu, Chenming Xu, Yang Wang
BACKGROUND: Human induced pluripotent stem cells (iPSCs) have been verified as a powerful cell model for the study of pathogenesis in hereditary disease. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD or non-PKD genes. The pathogenesis of ADPKD remains unexplored because of the lack of a true human cell model. METHODS: Six ADPKD patients and four healthy individuals were recruited as donors of somatic cells from a Chinese ADPKD family without mutations of the PKD genes but carrying SAMSN1 gene deletion...
September 19, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28923342/total-mercury-concentrations-in-liver-and-muscle-of-european-whitefish-coregonus-lavaretus-l-in-a-subarctic-lake-assessing-the-factors-driving-year-round-variation
#17
Ossi Keva, Brian Hayden, Chris Harrod, Kimmo K Kahilainen
Subarctic lakes are characterised by extreme seasonal variation in light and temperature which influences growth, maturation, condition and resource use of fishes. However, our understanding of how seasonal changes affect mercury concentrations of fishes is limited. We conducted a year-round study (3 ice-covered months, 3 open-water months) with open-water inter-annual aspect (3 years: samples from August/September), focusing on total mercury (THg) concentrations and ecological characteristics of a common freshwater fish, European whitefish (Coregonus lavaretus (L...
December 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28921784/the-evolution-of-gonad-expenditure-and-gonadosomatic-index-gsi-in-male-and-female-broadcast-spawning-invertebrates
#18
Geoff A Parker, Steven A Ramm, Jussi Lehtonen, Jonathan M Henshaw
Sedentary broadcast-spawning marine invertebrates, which release both eggs and sperm into the water for fertilization, are of special interest for sexual selection studies. They provide unique insight into the early stages of the evolutionary succession leading to the often-intense operation of both pre- and post-mating sexual selection in mobile gonochorists. Since they are sessile or only weakly mobile, adults can interact only to a limited extent with other adults and with their own fertilized offspring...
September 18, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28900770/how-regularities-of-mortality-statistics-explain-why-we-age-despite-having-potentially-ageless-somatic-stem-cells
#19
Alexander V Khalyavkin, Vyacheslav N Krut'ko
Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism's interaction with its environment...
September 12, 2017: Biogerontology
https://www.readbyqxmd.com/read/28877206/simulation-framework-for-generating-intratumor-heterogeneity-patterns-in-a-cancer-cell-population
#20
Watal M Iwasaki, Hideki Innan
As cancer cell populations evolve, they accumulate a number of somatic mutations, resulting in heterogeneous subclones in the final tumor. Understanding the mechanisms that produce intratumor heterogeneity is important for selecting the best treatment. Although some studies have involved intratumor heterogeneity simulations, their model settings differed substantially. Thus, only limited conditions were explored in each. Herein, we developed a general framework for simulating intratumor heterogeneity patterns and a simulator (tumopp)...
2017: PloS One
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