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Modelling somatic growth

Richard P Tan, Alex H P Chan, Katarina Lennartsson, Maria M Miravet, Bob S L Lee, Jelena Rnjak-Kovacina, Zoe E Clayton, John P Cooke, Martin K C Ng, Sanjay Patel, Steven G Wise
BACKGROUND: Induced pluripotent stem-cell derived endothelial cells (iPSC-ECs) can be generated from any somatic cell and their iPSC sources possess unlimited self-renewal. Previous demonstration of their proangiogenic activity makes them a promising cell type for treatment of ischemic injury. As with many other stem cell approaches, the low rate of in-vivo survival has been a major limitation to the efficacy of iPSC-ECs to date. In this study, we aimed to increase the in-vivo lifetime of iPSC-ECs by culturing them on electrospun polycaprolactone (PCL)/gelatin scaffolds, before quantifying the subsequent impact on their proangiogenic function...
March 21, 2018: Stem Cell Research & Therapy
Jennifer F Knight, Vanessa Y C Sung, Elena Kuzmin, Amber L Couzens, Danielle A de Verteuil, Colin D H Ratcliffe, Paula P Coelho, Radia M Johnson, Payman Samavarchi-Tehrani, Tina Gruosso, Harvey W Smith, Wontae Lee, Sadiq M Saleh, Dongmei Zuo, Hong Zhao, Marie-Christine Guiot, Ryan R Davis, Jeffrey P Gregg, Christopher Moraes, Anne-Claude Gingras, Morag Park
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro...
March 20, 2018: Cell Reports
Erica C Dresselhaus, Matthew C H Boersma, Mollie K Meffert
Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor kappa B (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine-enrichment (ΔSEp65) but retains inherent transcriptional activity equivalent to wild-type p65...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Joseph D Kuebler, Jill Shivapour, Selcen Yaroglu Kazanci, Kimberlee Gauvreau, Steven D Colan, Doff B McElhinney, David W Brown
BACKGROUND: Aortic stenosis has been reported to manifest a slow rate of progression in mild disease, with a greater likelihood of progression in patients with moderate-severe disease. The natural history of the Doppler-estimated maximum gradient (DEMG) in patients after balloon aortic valvuloplasty (BAVP) has not previously been studied on a large scale. METHODS AND RESULTS: A retrospective review was performed of 360 patients from 1984 to 2012 with aortic stenosis, providing a total of 2059 echocardiograms both before and after BAVP...
March 2018: Circulation. Cardiovascular Imaging
Daniel Cahill, Sevin Turcan
Malignant glioma is a common type of brain tumor that remains largely incurable. Although a definitive cell of origin of gliomas remains elusive, numerous population studies, sequencing efforts, and genetically engineered mouse models have contributed to our understanding of the early events that may lead to gliomagenesis. Herein we summarize our current knowledge on the population epidemiology of gliomas, heritable genetic risk factors, the somatic events that contribute to tumor evolution, and mouse models that have shed light on the glioma cell of origin...
February 2018: Seminars in Neurology
I M Côté, N S Smith
This review revisits the traits thought to have contributed to the success of Indo-Pacific lionfish Pterois sp. as an invader in the western Atlantic Ocean and the worst-case scenario about their potential ecological effects in light of the more than 150 studies conducted in the past 5 years. Fast somatic growth, resistance to parasites, effective anti-predator defences and an ability to circumvent predator recognition mechanisms by prey have probably contributed to rapid population increases of lionfish in the invaded range...
March 2018: Journal of Fish Biology
Patrick Kwok-Shing Ng, Jun Li, Kang Jin Jeong, Shan Shao, Hu Chen, Yiu Huen Tsang, Sohini Sengupta, Zixing Wang, Venkata Hemanjani Bhavana, Richard Tran, Stephanie Soewito, Darlan Conterno Minussi, Daniela Moreno, Kathleen Kong, Turgut Dogruluk, Hengyu Lu, Jianjiong Gao, Collin Tokheim, Daniel Cui Zhou, Amber M Johnson, Jia Zeng, Carman Ka Man Ip, Zhenlin Ju, Matthew Wester, Shuangxing Yu, Yongsheng Li, Christopher P Vellano, Nikolaus Schultz, Rachel Karchin, Li Ding, Yiling Lu, Lydia Wai Ting Cheung, Ken Chen, Kenna R Shaw, Funda Meric-Bernstam, Kenneth L Scott, Song Yi, Nidhi Sahni, Han Liang, Gordon B Mills
The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes...
March 12, 2018: Cancer Cell
Mykyta Artomov, Alexander J Stratigos, Ivana Kim, Raj Kumar, Martin Lauss, Bobby Y Reddy, Benchun Miao, Carla Daniela Robles-Espinoza, Aravind Sankar, Ching-Ni Njauw, Kristen Shannon, Evangelos S Gragoudas, Anne Marie Lane, Vivek Iyer, Julia A Newton-Bishop, D Timothy Bishop, Elizabeth A Holland, Graham J Mann, Tarjinder Singh, Mark J Daly, Hensin Tsao
Background: Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM). Methods: Using 11 990 jointly processed individual DNA samples, whole-exome sequencing was performed, followed by large-scale joint variant calling using GATK (Genome Analysis ToolKit)...
December 1, 2017: Journal of the National Cancer Institute
Liansheng Liu, Yaohui Zhu, Michaël Noë, Qian Li, Pankaj Jay Pasricha
BACKGROUND & AIMS: Chronic pancreatitis (CP) is characterized by pancreatic inflammation and fibrosis, associated with increased pancreatic expression of transforming growth factor beta (TGFB). It is not clear how these might contribute to pain. We investigated whether TGFB signaling via SMAD induces sensitization of pancreatic sensory neurons to increase nociception. METHODS: CP was induced in Sprague-Dawley rats by infusion of trinitrobenzene sulfonic acid; some rats were given intrathecal infusions of TGFB1...
March 2, 2018: Gastroenterology
Paul N Manley, Suzan Abu-Abed, Richard Kirsch, Andrea Hawrysh, Nicole Perrier, Harriet Feilotter, Aaron Pollett, Robert Riddell, Lawrence Hookey, Jagdeep S Walia
Germline activating platelet derived growth factor receptor alpha (PDGFRA) mutations have been described in four families. All the index patients have presented with multiple mesenchymal tumors of the gastrointestinal tract. We identified a fifth family with four first-degree relatives that harbor a PDGFRA exon 18 (D846V) germline mutation. The affected kindred have a unique phenotype including coarse facies and skin, broad hands and feet, and previously undescribed premature tooth loss. While the index patient presented with multiple small bowel inflammatory fibroid polyps (IFPs) and has a gastric gastrointestinal stromal tumor (GIST), no tumors have yet been identified in other family members...
February 24, 2018: Human Pathology
Benjamin J Drapkin, Julie George, Camilla L Christensen, Mari Mino-Kenudson, Ruben Dries, Tilak Sundaresan, Sarah Phat, David T Myers, Jun Zhong, Peter Igo, Mehlika H Hazar-Rethinam, Joseph A LiCausi, Maria Gomez-Caraballo, Marina Kem, Kandarp N Jani, Roxana Azimi, Nima Abedpour, Roopika Menon, Sotirios Lakis, Rebecca S Heist, Reinhard Büttner, Stefan Haas, Lecia V Sequist, Alice T Shaw, Kwok-Kin Wong, Aaron N Hata, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber, Martin Peifer, Nicholas Dyson, Roman K Thomas, Anna F Farago
Small cell lung cancer (SCLC) patient-derived xenografts (PDXs) can be generated from biopsies or circulating tumor cells (CTCs), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC-enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a two-year timeframe, at 89% and 38% efficiency, respectively. Whole exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs...
February 26, 2018: Cancer Discovery
Honghao Yu, Weihu Long, Xuezeng Zhang, Kaixiang Xu, Jianxiong Guo, Heng Zhao, Honghui Li, Yubo Qing, Weirong Pan, Baoyu Jia, Hong-Ye Zhao, Xingxu Huang, Hong-Jiang Wei
BACKGROUND: Laron syndrome is an autosomal disease resulting from mutations in the growth hormone receptor (GHR) gene. The only therapeutic treatment for Laron syndrome is recombinant insulin-like growth factor I (IGF-I), which has been shown to have various side effects. The improved Laron syndrome models are important for better understanding the pathogenesis of the disease and developing corresponding therapeutics. Pigs have become attractive biomedical models for human condition due to similarities in anatomy, physiology, and metabolism relative to humans, which could serve as an appropriate model for Laron syndrome...
February 27, 2018: Journal of Translational Medicine
Luiz Henrique de Castro Assis, Rafael Henrique Nobrega, Nuria Esther Gómez-González, Jan Bogerd, Rüdiger Schulz
The hormonal regulation of spermatogenesis involves both gonadotropins and steroid hormones. Long-term in vivo exposure of adult zebrafish to estrogen impaired spermatogenesis associated with an androgen insufficiency, possibly induced by inhibiting gonadotropin release. Using this experimental model, we investigated if androgen treatment could enhance spermatogenesis, while maintaining the inhibition of gonadotropin release through continued estrogen exposure. Moreover, we also exposed animals to androgen alone, in order to examine androgen effects in the absence of estrogen-induced gonadotropin inhibition...
February 23, 2018: Journal of Molecular Endocrinology
Peter C van den Akker, Anna M G Pasmooij, Hans Joenje, Robert M W Hofstra, Gerard J Te Meerman, Marcel F Jonkman
Revertant mosaicism, or "natural gene therapy", is the phenomenon in which germline mutations are corrected by somatic events. In recent years, revertant mosaicism has been identified in all major types of epidermolysis bullosa, the group of heritable blistering disorders caused by mutations in the genes encoding epidermal adhesion proteins. Moreover, revertant mosaicism appears to be present in all patients with a specific subtype of recessive epidermolysis bullosa. We therefore hypothesized that revertant mosaicism should be expected at least in all patients with recessive forms of epidermolysis bullosa...
2018: PloS One
Elena Viganò, Jay Gunawardana, Anja Mottok, Tessa Van Tol, Katina Mak, Fong Chun Chan, Lauren Chong, Elizabeth Chavez, Bruce Woolcock, Katsuyoshi Takata, David Twa, Hennady P Shulha, Adèle Telenius, Olga Kutovaya, Stacy S Hung, Shannon Healy, Susana Ben-Neriah, Karen Leroy, Philippe Gaulard, Arjan Diepstra, Robert Kridel, Kerry J Savage, Lisa Rimsza, Randy Gascoyne, Christian Steidl
Primary mediastinal large B cell lymphoma (PMBCL) is a distinct subtype of diffuse large B cell lymphoma thought to arise from thymic medullary B cells. Gene mutations underlying the molecular pathogenesis of the disease are incompletely characterized. Here, we describe novel somatic IL4R mutations in 15 out of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested. The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in exon 8 leading to an I242N amino acid change in the transmembrane domain...
February 21, 2018: Blood
Sandra Bibiana Correa, Kirk Winemiller
Despite low in situ primary productivity, tropical oligotrophic rivers support highly diverse fish assemblages and productive fisheries. This raises the question, what energy sources support fish production in these ecosystems? We sampled fish and food resources in the floodplain of a nearly pristine, large, oligotrophic river in western Amazonia. We combined data from stomach contents and stable isotopes to test the hypothesis that floodplain forests sustain fisheries in tropical oligotrophic rivers. Analysis of stomach contents from > 800 specimens of 12 omnivorous fish species demonstrated that during the annual flood, forest plant matter dominated diets...
February 17, 2018: Oecologia
Jonathan P Auld, James O Mudd, Jill M Gelow, Karen S Lyons, Shirin O Hiatt, Christopher S Lee
BACKGROUND: Both heart failure symptoms and self-care are associated with patient outcomes. Although it is thought that symptoms drive self-care, there is limited evidence to support this assumption over time. AIMS: To determine whether patterns of physical symptoms are significantly associated with heart failure self-care over time. METHOD: Latent mixture analysis was used to identify subgroups based on physical symptoms of dyspnea, sleepiness and edema (using the heart failure somatic perception and Epworth sleepiness scales)...
February 1, 2018: European Journal of Cardiovascular Nursing
Masoome Jabarpour, Parviz Tajik
Background: The complex process of spermatogenesis is regulated by various factors. Several studies have been conducted to proliferate cells involved in the spermatogenesis process, in culture by used growth factors, different hormones and feeder cells. This study was conducted to evaluate the role of Sertoli cells on gene expression of fibroblast growth factor (FGF2) and glial cell derived neurotrophic factor (GDNF) after removal of spermatogonial stem cells (SSCs) from the culture medium...
2018: Stem Cell Investigation
Linsey M Arnold, Wade D Smith, Paul D Spencer, Allison N Evans, Scott A Heppell, Selina S Heppell
Despite evidence of maternal age effects in a number of teleost species, there have been challenges to the assertion that maternal age intrinsically influences offspring quality. From an evolutionary perspective, maternal age effects result in young females paradoxically investing in less fit offspring despite a greater potential fitness benefit that might be gained by allocating this energy to individual somatic growth. Although a narrow range of conditions could lead to a maternal fitness benefit via the production of lower quality offspring, evolutionary theorists suggest these conditions are seldom met and that the reported maternal age effects are more likely products of the environmental context...
January 2018: Royal Society Open Science
Martino Belvederi Murri, Pantaleimon Ekkekakis, Marco Menchetti, Francesca Neviani, Fausto Trevisani, Stefano Tedeschi, Pasqualino Maietta Latessa, Erika Nerozzi, Giuliano Ermini, Donato Zocchi, Salvatore Squatrito, Giulio Toni, Aderville Cabassi, Mirco Neri, Stamatula Zanetidou, Mario Amore
BACKGROUND: Physical exercise is increasingly recognized as a treatment for major depression, even among older patients. However, it is still unknown which depressive symptoms exercise affects most, (e.g. somatic vs. affective) and the timing of its effects. Thus, the aim of this study was to examine the changes of depressive symptoms after treatment with exercise. METHODS: We analyzed data from the SEEDS study, a trial comparing the antidepressant effectiveness of sertraline (S) and sertraline plus exercise (S+EX)...
January 26, 2018: Journal of Affective Disorders
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