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Modelling somatic growth

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https://www.readbyqxmd.com/read/28214862/differential-clonal-expansion-in-an-invading-cell-population-clonal-advantage-or-dumb-luck
#1
Donald F Newgreen, Dongcheng Zhang, Bevan L Cheeseman, Benjamin J Binder, Kerry A Landman
In neoplastic cell growth, clones and subclones are variable both in size and mutational spectrum. The largest of these clones are believed to represent those cells with mutations that make them the most "fit," in a Darwinian sense, for expansion in their microenvironment. Thus, the degree of quantitative clonal expansion is regarded as being determined by innate qualitative differences between the cells that originate each clone. Here, using a combination of mathematical modelling and clonal labelling experiments applied to the developmental model system of the forming enteric nervous system, we describe how cells which are qualitatively identical may consistently produce clones of dramatically different sizes: most clones are very small while a few clones we term "superstars" contribute most of the cells to the final population...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28202529/aberrant-syk-kinase-signaling-is-essential-for-tumorigenesis-induced-by-tsc2-inactivation
#2
Ye Cui, Wendy K Steagall, Anthony Lamattina, Gustavo Pacheco-Rodriguez, Mario Stylianou, Pranav Kidambi, Benjamin Stump, Fernanda Golzarri, Ivan O Rosas, Carmen Priolo, Elizabeth P Henske, Joel Moss, Souheil El-Chemaly
Somatic or germline mutations in the tuberous sclerosis complex (TSC) tumor suppressor genes are associated closely with the pathogenesis of lymphangioleiomyomatosis (LAM), a rare and progressive neoplastic disease that predominantly affects women in their childbearing years. Serum levels of the lymphangiogeneic growth factor VEGF-D are elevated significantly in LAM. However, there are gaps in knowledge regarding VEGF-D dysregulation and its cellular origin in LAM. Here we show that increased expression and activation of the tyrosine kinase Syk in TSC2-deficient cells and pulmonary nodules from LAM patients contributes to tumor growth...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196408/somatic-mutations-in-murine-models-of-leukemia-and-lymphoma-disease-specificity-and-clinical-relevance
#3
Liat Goldberg, Sheryl M Gough, Fan Lee, Christine Dang, Robert L Walker, Yeulin J Zhu, Sven Bilke, Marbin Pineda, Masahiro Onozawa, Yang Jo Chung, Paul S Meltzer, Peter D Aplan
Malignant transformation is a multistep process that is dictated by acquisition of multiple genomic aberrations that provide growth and survival advantage. During the post genomic era, high throughput genomic sequencing has advanced exponentially, leading to identification of countless cancer associated mutations with potential for targeted therapy. Mouse models of cancer serve as excellent tools to examine the functionality of gene mutations and their contribution to the malignant process. However, it remains unclear whether the genetic events that occur during transformation are similar in mice and humans...
February 14, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28195550/novel-germline-mutation-leu512met-in-the-thyrotropin-receptor-gene-tshr-leading-to-sporadic-non-autoimmune-hyperthyroidism
#4
Stephanie A Roberts, Jennifer E Moon, Andrew Dauber, Jessica R Smith
BACKGROUND: Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in the TSHR gene who presented with accelerated growth, enlarging head circumference, tremor and thyrotoxicosis...
February 14, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28193767/the-role-of-nuclear-receptor-binding-set-domain-family-histone-lysine-methyltransferases-in-cancer
#5
Richard L Bennett, Alok Swaroop, Catalina Troche, Jonathan D Licht
The nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyltransferases is comprised of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1). These enzymes recognize and catalyze methylation of histone lysine marks to regulate chromatin integrity and gene expression. The growing number of reports demonstrating that alterations or translocations of these genes fundamentally affect cell growth and differentiation leading to developmental defects illustrates the importance of this family. In addition, overexpression, gain of function somatic mutations, and translocations of NSDs are associated with human cancer and can trigger cellular transformation in model systems...
February 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28176142/hmgb1-tlr4-axis-plays-a-regulatory-role-in-the-pathogenesis-of-mesial-temporal-lobe-epilepsy-in-immature-rat-model-and-children-via-the-p38mapk-signaling-pathway
#6
Weihong Yang, Jing Li, Yun Shang, Li Zhao, Mingying Wang, Jipeng Shi, Shujun Li
The HMGB1-TLR4 axis is activated in adult mouse models of acute and chronic seizure. Nevertheless, whether HMGB1 was involved in the pathogenesis of mesial temporal lobe epilepsy (MTLE) remains unknown. In this study, we first measured the dynamic expression patterns of HMGB1 and TLR4 in the hippocampi of a rat model and in children with MTLE, as well as the levels of TNF-α and IL-1β. In addition, HMGB1 was added to mimic the process of inflammatory response in neurons. Neuronal somatic size and dendritic length were measured by immunohistochemistry and digital imaging...
February 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28161602/characterizing-mandibular-growth-using-three-dimensional-imaging-techniques-and-anatomic-landmarks
#7
Michael P Kelly, Houri K Vorperian, Yuan Wang, Katelyn K Tillman, Helen M Werner, Moo K Chung, Lindell R Gentry
OBJECTIVE: To provide quantitative data on the multi-planar growth of the mandible, this study derived accurate linear and angular mandible measurements using landmarks on three dimensional (3D) mandible models. This novel method was used to quantify 3D mandibular growth and characterize the emergence of sexual dimorphism. DESIGN: Cross-sectional and longitudinal imaging data were obtained from a retrospective computed tomography (CT) database for 51 typically developing individuals between the ages of one and nineteen years...
January 23, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28111236/prevalence-of-prediabetes-risk-in-offspring-born-to-mothers-with-hyperandrogenism
#8
Shen Tian, Xian-Hua Lin, Yi-Meng Xiong, Miao-E Liu, Tian-Tian Yu, Min Lv, Wei Zhao, Gu-Feng Xu, Guo-Lian Ding, Chen-Ming Xu, Min Jin, Chun Feng, Yan-Ting Wu, Ya-Jing Tan, Qian Gao, Jian Zhang, Cheng Li, Jun Ren, Lu-Yang Jin, Bin Chen, Hong Zhu, Xue-Ying Zhang, Song-Chang Chen, Xin-Mei Liu, Ye Liu, Jun-Yu Zhang, Li Wang, Ping Zhang, Xiao-Jun Chen, Li Jin, Xi Chen, Yi-Cong Meng, Dan-Dan Wu, Hui Lin, Qian Yang, Cheng-Liang Zhou, Xin-Zhu Li, Yi-Yu Wang, Yu-Qian Xiang, Zhi-Wei Liu, Ling Gao, Lu-Ting Chen, Hong-Jie Pan, Rong Li, Fang-Hong Zhang, Lan-Feng Xing, Yi-Min Zhu, Christian Klausen, Peter C K Leung, Ju-Xue Li, Fei Sun, Jian-Zhong Sheng, He-Feng Huang
BACKGROUND: Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. METHODS: Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010...
January 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28108485/tgf-%C3%AE-family-signaling-in-embryonic-and-somatic-stem-cell-renewal-and-differentiation
#9
Alan C Mullen, Jeffrey L Wrana
Soon after the discovery of transforming growth factor-β (TGF-β), seminal work in vertebrate and invertebrate models revealed the TGF-β family to be central regulators of tissue morphogenesis. Members of the TGF-β family direct some of the earliest cell-fate decisions in animal development, coordinate complex organogenesis, and contribute to tissue homeostasis in the adult. Here, we focus on the role of the TGF-β family in mammalian stem-cell biology and discuss its wide and varied activities both in the regulation of pluripotency and in cell-fate commitment...
January 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28087716/the-piggybac-transposon-derived-genes-tpb1-and-tpb6-mediate-essential-transposon-like-excision-during-the-developmental-rearrangement-of-key-genes-in-tetrahymena-thermophila
#10
Chao-Yin Cheng, Janet M Young, Chih-Yi Gabriela Lin, Ju-Lan Chao, Harmit S Malik, Meng-Chao Yao
Ciliated protozoans perform extreme forms of programmed somatic DNA rearrangement during development. The model ciliate Tetrahymena thermophila removes 34% of its germline micronuclear genome from somatic macronuclei by excising thousands of internal eliminated sequences (IESs), a process that shares features with transposon excision. Indeed, piggyBac transposon-derived genes are necessary for genome-wide IES excision in both Tetrahymena (TPB2 [Tetrahymena piggyBac-like 2] and LIA5) and Paramecium tetraurelia (PiggyMac)...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28074003/dna-polymerase-beta-germline-variant-confers-cellular-response-to-cisplatin-therapy
#11
Antonia A Nemec, Laura Abriola, Jane S Merkel, Elisa deStanchina, Michelle DeVeaux, Daniel Zelterman, Peter M Glazer, Joann B Sweasy
: Resistance to cancer chemotherapies leads to deadly consequences, yet current research focuses only on the roles of somatically acquired mutations in this resistance. The mutational status of the germline is also likely to play a role in the way cells respond to chemotherapy. The carrier status for the POLB rs3136797 germline mutation encoding P242R DNA polymerase beta (Pol β) is associated with poor prognosis for lung cancer, specifically in response to treatment with cisplatin. Here, it is revealed that the P242R mutation is sufficient to promote resistance to cisplatin in human cells and in mouse xenografts...
January 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28070867/analytical-modeling-for-computing-lead-stress-in-a-novel-epicardial-micropacemaker
#12
Li Zhou, Yaniv Bar-Cohen, Raymond A Peck, Giorgio V Chirikian, Brett Harwin, Ramen H Chmait, Jay D Pruetz, Michael J Silka, Gerald E Loeb
Implantation and maintenance of a permanent cardiac pacing system in children remains challenging due to small patient size, congenital heart defects and somatic growth. We are developing a novel epicardial micropacemaker for children that can be implanted on the epicardium within the pericardial space via a minimally-invasive technique. The key design configurations include a novel open-coiled lead in which living tissue replaces the usual polymeric support for the coiled conductor. To better understand and be able to predict the behavior of the implanted lead, we performed a radiographic image-based modeling study on a chronic animal test...
March 2017: Cardiovascular Engineering and Technology
https://www.readbyqxmd.com/read/28053272/trans-generational-function-of-tetrahymena-piwi-protein-twi8p-at-distinctive-non-coding-rna-loci
#13
Brian M Farley, Kathleen Collins
Trans-generational transmission of genome-regulatory epigenetic information can determine phenotypes in the progeny of sexual reproduction. Sequence specificity of trans-generational regulation derives from small RNAs assembled into Piwi-protein complexes. Known targets of trans-generational regulation are primarily transposons and transposon-derived sequences. Here, we extend the scope of Piwi-mediated trans-generational regulation to include unique non-coding RNA loci. Ciliates such as Tetrahymena have a phenotypically silent germline micronucleus and an expressed somatic macronucleus, which is differentiated anew from a germline genome copy in sexual reproduction...
January 4, 2017: RNA
https://www.readbyqxmd.com/read/28011715/generation-of-hoxc13-knockout-pigs-recapitulates-human-ectodermal-dysplasia-9
#14
Kai Han, Liuping Liang, Li Li, Zhen Ouyang, Bentian Zhao, Qi Wang, Zhaoming Liu, Yu Zhao, Xiaoshuai Ren, Fei Jiang, Chengdan Lai, Kepin Wang, Sen Yan, Liang Huang, Lin Guo, Kang Zeng, Liangxue Lai, Nana Fan
Atrichia and sparse hair phenotype cause distress to many patients. Ectodermal dysplasia-9 (ED-9) is a congenital condition characterized by hypotrichosis and nail dystrophy without other disorders, and Hoxc13 is a pathogenic gene for ED-9. However, mice carrying Hoxc13 mutation present several other serious disorders, such as skeletal defects, progressive weight loss and low viability. Mouse models cannot faithfully mimic human ED-9. In this study, we generated an ED-9 pig model via Hoxc13 gene knockout through single-stranded oligonucleotides (c...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28009305/probabilistic-modeling-of-reprogramming-to-induced-pluripotent-stem-cells
#15
Lin L Liu, Justin Brumbaugh, Ori Bar-Nur, Zachary Smith, Matthias Stadtfeld, Alexander Meissner, Konrad Hochedlinger, Franziska Michor
Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is typically an inefficient and asynchronous process. A variety of technological efforts have been made to accelerate and/or synchronize this process. To define a unified framework to study and compare the dynamics of reprogramming under different conditions, we developed an in silico analysis platform based on mathematical modeling. Our approach takes into account the variability in experimental results stemming from probabilistic growth and death of cells and potentially heterogeneous reprogramming rates...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27998972/looking-beyond-drivers-and-passengers-in-cancer-genome-sequencing-data
#16
S De, S Ganesan
Cancer arises as a result of acquired changes in the DNA sequence of the genome of somatic cells. A subset of the genetic changes, dubbed driver mutations, propels tumor growth, and the remaining changes are passengers, apparently inconsequential for neoplastic transformation. Massive genome sequencing of thousands of tumors from all major cancer types has enabled cataloging of the so-called driver and passenger mutations, and facilitated molecular classification of cancer, guiding precision medicine approach for the patients...
December 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27973729/accurate-estimates-of-age-at-maturity-from-the-growth-trajectories-of-fishes-and-other-ectotherms
#17
Andrew E Honsey, David F Staples, Paul A Venturelli
Age at maturity (AAM) is a key life history trait that provides insight into ecology, evolution, and population dynamics. However, maturity data can be costly to collect or may not be available. Life history theory suggests that growth is biphasic for many organisms, with a change-point in growth occurring at maturity. If so, then it should be possible to use a biphasic growth model to estimate AAM from growth data. To test this prediction, we used the Lester biphasic growth model in a likelihood profiling framework to estimate AAM from length at age data...
August 26, 2016: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/27940616/dissecting-the-transcriptional-patterns-of-social-dominance-across-teleosts
#18
Suzy C P Renn, Cynthia F O'Rourke, Nadia Aubin-Horth, Eleanor J Fraser, Hans A Hofmann
In many species, under varying ecological conditions, social interactions among individuals result in the formation of dominance hierarchies. Despite general similarities, there are robust differences among dominance hierarchies across species, populations, environments, life stages, sexes, and individuals. Understanding the proximate mechanisms underlying the variation is an important step toward understanding the evolution of social behavior. However, physiological changes associated with dominance, such as gonadal maturation and somatic growth, often complicate efforts to identify the specific underlying mechanisms...
December 2016: Integrative and Comparative Biology
https://www.readbyqxmd.com/read/27935819/a-novel-brain-tumour-model-in-zebrafish-reveals-the-role-of-yap-activation-in-mapk-and-pi3k-induced-malignant-growth
#19
Marie Mayrhofer, Victor Gourain, Markus Reischl, Pierre Affaticati, Arnim Jenett, Jean-Stephane Joly, Matteo Benelli, Francesca Demichelis, Pietro Luigi Poliani, Dirk Sieger, Marina Mione
Somatic mutations activating MAPK and PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed a zebrafish model of brain tumours based on somatic expression of oncogenes that activate MAPK and PI3K signalling in neural progenitor cells and found that HRAS(V12) was the most effective in inducing both heterotopia and invasive tumours. Tumours, but not heterotopias, require persistent activation of phospho (p)-ERK and express a gene signature similar to the mesenchymal glioblastoma subtype, with a strong YAP component...
January 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27935184/impaired-ecosystem-process-despite-little-effects-on-populations-modeling-combined-effects-of-warming-and-toxicants
#20
Nika Galic, Volker Grimm, Valery E Forbes
Freshwater ecosystems are exposed to many stressors, including toxic chemicals and global warming, which can impair, separately or in combination, important processes in organisms and hence higher levels of organization. Investigating combined effects of warming and toxicants has been a topic of little research, but neglecting their combined effects may seriously misguide management efforts. To explore how toxic chemicals and warming, alone and in combination, propagate across levels of biological organization, including a key ecosystem process, we developed an individual-based model (IBM) of a freshwater amphipod detritivore, Gammarus pseudolimnaeus, feeding on leaf litter...
December 9, 2016: Global Change Biology
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