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Modelling somatic growth

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https://www.readbyqxmd.com/read/28615336/prevention-and-reversal-of-latent-sensitization-of-dorsal-horn-neurons-by-glial-blockers-in-a-model-of-low-back-pain-in-male-rats
#1
Juanjuan Zhang, Siegfried Mense, Rolf-Detlef Treede, Ulrich Hoheisel
In an animal model of non-specific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues...
June 14, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28611049/comprehensive-evaluation-of-protein-coding-mononucleotide-microsatellites-in-microsatellite-unstable-colorectal-cancer
#2
Johanna Kondelin, Alexandra E Gylfe, Sofie Lundgren, Tomas Tanskanen, Jiri Hamberg, Mervi Aavikko, Kimmo Palin, Heikki Ristolainen, Riku Katainen, Eevi Kaasinen, Minna Taipale, Jussi Taipale, Laura Renkonen-Sinisalo, Heikki Järvinen, Jan Böhm, Jukka-Pekka Mecklin, Pia Vahteristo, Sari Tuupanen, Lauri A Aaltonen, Esa Pitkänen
<span style="background-color: white;">Approximately 15% of colorectal cancers (CRC) exhibit microsatellite instability (MSI), which leads to accumulation of a large numbers of small insertions and deletions (indels). Genes that provide growth advantage to cells via loss-of-function mutations in microsatellites are called MSI target genes. Several criteria to define these genes have been suggested, one of them being simple mutation frequency. Microsatellite mutation rate, however, depends on the length and nucleotide context of the microsatellite...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28595192/cancer-precision-medicine-why-more-is-more-and-dna-is-not-enough
#3
Moritz Schütte, Lesley A Ogilvie, Damian T Rieke, Bodo M H Lange, Marie-Laure Yaspo, Hans Lehrach
Every tumour is different. They arise in patients with different genomes, from cells with different epigenetic modifications, and by random processes affecting the genome and/or epigenome of a somatic cell, allowing it to escape the usual controls on its growth. Tumours and patients therefore often respond very differently to the drugs they receive. Cancer precision medicine aims to characterise the tumour (and often also the patient) to be able to predict, with high accuracy, its response to different treatments, with options ranging from the selective characterisation of a few genomic variants considered particularly important to predict the response of the tumour to specific drugs, to deep genome analysis of both tumour and patient, combined with deep transcriptome analysis of the tumour...
June 9, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28592566/combined-immune-checkpoint-blockade-as-a-therapeutic-strategy-for-brca1-mutated-breast-cancer
#4
Emma Nolan, Peter Savas, Antonia N Policheni, Phillip K Darcy, François Vaillant, Christopher P Mintoff, Sathana Dushyanthen, Mariam Mansour, Jia-Min B Pang, Stephen B Fox, Charles M Perou, Jane E Visvader, Daniel H D Gray, Sherene Loi, Geoffrey J Lindeman
Immune checkpoint inhibitors have emerged as a potent new class of anticancer therapy. They have changed the treatment landscape for a range of tumors, particularly those with a high mutational load. To date, however, modest results have been observed in breast cancer, where tumors are rarely hypermutated. Because BRCA1-associated tumors frequently exhibit a triple-negative phenotype with extensive lymphocyte infiltration, we explored their mutational load, immune profile, and response to checkpoint inhibition in a Brca1-deficient tumor model...
June 7, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28560692/engineering-kidney-cells-reprogramming-and-directed-differentiation-to-renal-tissues
#5
REVIEW
Michael M Kaminski, Jelena Tosic, Roman Pichler, Sebastian J Arnold, Soeren S Lienkamp
Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons...
July 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28539836/dual-delivery-of-ngf-and-bfgf-coacervater-ameliorates-diabetic-peripheral-neuropathy-via-inhibiting-schwann-cells-apoptosis
#6
Rui Li, Jianfeng Ma, Yanqing Wu, Matthew Nangle, Shuang Zou, Yiyang Li, Jiayu Yin, Yingzheng Zhao, Helin Xu, Hongyu Zhang, Xiaokun Li, Qing Song Ye, Jian Wang, Jian Xiao
Diabetic neuropathy is a kind of insidious complications that impairs neural and vascular function and ultimately leads to somatic and visceral denervation. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are important neurotrophic factors for stimulating angiogenesis and improving peripheral nerve function. Administrating a single factor has good therapeutic effect on diabetic peripheral neuropathy (DPN). However, the short half-life and rapid diffusion of growth factors under physiological conditions limits its clinical applications...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28536279/the-damaging-effect-of-passenger-mutations-on-cancer-progression
#7
Christopher McFarland, Julia A Yaglom, Jonathan W Wojtkowiak, Jacob Scott, David L Morse, Michael Y Sherman, Leonid Mirny
Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution, most are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522754/met-exon-14-mutation-encodes-an-actionable-therapeutic-target-in-lung-adenocarcinoma
#8
Xinyuan Lu, Nir Peled, John Greer, Wei Wu, Peter Choi, Alice H Berger, Sergio Wong, Kuang-Yu Jen, Youngho Seo, Byron Hann, Angela Brooks, Matthew Meyerson, Eric A Collisson
Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METΔ14). Here we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METΔ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a Hepatocyte growth factor (HGF)-dependent manner...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28520540/virtual-surgery-for-conduit-reconstruction-of-the-right-ventricular-outflow-tract
#9
Chin Siang Ong, Yue-Hin Loke, Justin Opfermann, Laura Olivieri, Luca Vricella, Axel Krieger, Narutoshi Hibino
PURPOSE: Virtual surgery involves the planning and simulation of surgical reconstruction using three-dimensional (3D) modeling based upon individual patient data, augmented by simulation of planned surgical alterations including implantation of devices or grafts. Here we describe a case in which virtual cardiac surgery aided us in determining the optimal conduit size to use for the reconstruction of the right ventricular outflow tract. DESCRIPTION: The patient is a young adolescent male with a history of tetralogy of Fallot with pulmonary atresia, requiring right ventricle-to-pulmonary artery (RV-PA) conduit replacement...
May 2017: World Journal for Pediatric & Congenital Heart Surgery
https://www.readbyqxmd.com/read/28501635/determining-the-role-of-inflammation-in-the-selection-of-jak2-mutant-cells-in-myeloproliferative-neoplasms
#10
Jie Zhang, Angela G Fleischman, Dominik Wodarz, Natalia L Komarova
Myeloproliferative neoplasm (MPN) is a hematologic malignancy characterized by the clonal outgrowth of hematopoietic cells with a somatically acquired mutation most commonly in JAK2 (JAK2(V617F)). This mutation endows upon myeloid progenitors cytokine independent growth and consequently leads to excessive production of myeloid lineage cells. It has been previously suggested that inflammation may play a role in the clonal evolution of JAK2(V617F) mutants. In particular, it is possible that one or more cellular kinetic parameters of hematopoietic stem cells (HSCs) are affected by inflammation, such as division or death rates of cells, and the probability of HSC differentiation...
July 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28487443/her2-reactivation-through-acquisition-of-the-her2-l755s-mutation-as-a-mechanism-of-acquired-resistance-to-her2-targeted-therapy-in-her2-breast-cancer
#11
Xiaowei Xu, Carmine De Angelis, Kathleen A Burke, Agostina Nardone, Huizhong Hu, Lanfang Qin, Jamunarani Veeraraghavan, Vidyalakshmi Sethunath, Laura M Heiser, Nicholas J Wang, Charlotte K Y Ng, Edward Chen, Alexander Renwick, Tao Wang, Sarmistha Nanda, Martin Shea, Tamika Mitchell, Mahitha Rajendran, Ian Waters, Daniel J Zabransky, Kenneth L Scott, Carolina Gutierrez, Chandandeep Nagi, Felipe C Geyer, Gary C Chamness, Ben Ho Park, Chad Shaw, Susan G Hilsenbeck, Mothaffar F Rimawi, Joe W Gray, Britta Weigelt, Jorge S Reis-Filho, C Kent Osborne, Rachel Schiff
Purpose: Resistance to anti-HER2 therapies in HER2+ breast cancer can occur through activation of alternative survival pathways or reactivation of the HER signaling network. Here we employed BT474 parental and treatment-resistant cell line models to investigate a mechanism by which HER2+ breast cancer can reactivate the HER network under potent HER2-targeted therapies. <p>Experimental Design: Resistant derivatives to lapatinib (L), trastuzumab (T), or the combination (LR/TR/LTR) were developed independently from two independent estrogen receptor ER+/HER2+ BT474 cell lines (AZ/ATCC)...
May 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28475811/ablation-of-hepatic-production-of-the-acid-labile-subunit-in-the-bovine-gh-transgenic-mice-effects-on-organ-and-skeletal-growth
#12
Zhongbo Liu, Tianzhen Han, Shannon Fishman, James Butler, Tracy Zimmermann, Frederic Tremblay, Carole Harbison, Nidhi Agrawal, John J Kopchick, Mitchell B Schaffler, Shoshana Yakar
Growth hormone (GH) and insulin like growth factor-1 (IGF-1) are anabolic hormones that facilitate somatic and skeletal growth, and regulate metabolism via endocrine and autocrine/paracrine mechanisms. We hypothesized that excess tissue production of GH will protect skeletal growth and integrity in states of reductions in serum IGF-1 levels. To test our hypothesis we used the bovine GH (bGH) transgenic mice as a model of GH hypersecretion and ablated the liver-derived acid labile subunit (ALS), which stabilizes IGF-1 complexes with IGF-binding protein-3 (IGFBP-3) and -5 in circulation...
May 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28472809/developmental-changes-in-expression-of-gabaa-receptor-subunits-%C3%AE-1-%C3%AE-2-and-%C3%AE-3-in-the-pig-brain
#13
Stephanie M Miller, Viskasari P Kalanjati, Paul B Colditz, Stella Tracey Björkman
GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABAA receptor (GABAAR); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABAA α-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97, 100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days)...
May 5, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28424200/whole-exome-sequencing-of-metaplastic-breast-carcinoma-indicates-monoclonality-with-associated-ductal-carcinoma-component
#14
Bracha Avigdor, Katie Beierl, Christopher D Gocke, Daniel Zabransky, Karen Cravero, Kelly Kyker-Snowman, Berry Button, David Chu, Sarah Croessmann, Rory L Cochran, Roisin Connolly, Ben Ho Park, Ashley Cimino-Mathews, Sarah J Wheelan
Although most human cancers display a single histology, there are unusual cases where two or more distinct tissue types present within a primary tumor. One such example is metaplastic breast carcinoma, a rare but aggressive cancer with a heterogenous histology, including squamous, chondroid, and spindle cells. Metaplastic carcinomas often contain an admixed conventional ductal invasive or in situ mammary carcinoma component, and are typically triple-negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER-2) amplification/overexpression...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28414787/water-abstraction-affects-abundance-size-structure-and-growth-of-two-threatened-cyprinid-fishes
#15
Roberto Merciai, Carlota Molons-Sierra, Sergi Sabater, Emili García-Berthou
Hydrologic alteration is a major threat to freshwater biota, and particularly fish, in many river courses around the world. We analyzed and compared the effects of water abstraction on two threatened cyprinid fishes of contrasting ecology (the Mediterranean barbel Barbus meridionalis and the Catalan chub Squalius laietanus) in a Mediterranean stream. We compared abundance, size-structure, growth, and condition of both species across perennial and artificially intermittent reaches affected by water abstraction...
2017: PloS One
https://www.readbyqxmd.com/read/28410228/identification-of-a-novel-functional-jak1-s646p-mutation-in-acute-lymphoblastic-leukemia
#16
Qian Li, Botao Li, Liangding Hu, Hongmei Ning, Min Jiang, Danhong Wang, Tingting Liu, Bin Zhang, Hu Chen
The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406502/self-regulatory-factors-of-embryonic-stem-cells-in-co-culture-with-stromal-cells-enhance-neural-differentiation
#17
R Joshi, J C Buchanan, H Tavana
Embryonic stem cells (ESCs), due to their intrinsic capability to generate somatic cells of all three germ layers, are potential sources of neural cells for cell replacement therapies. However, the empirical differentiation protocols and the lack of mechanistic understanding of the neural differentiation of ESCs have limited the utility of ESCs as a developmental model or as a cell source for neural cell populations for replacement therapies. Co-culturing ESCs with stromal cells is one of the extensively used methods to induce neural differentiation...
May 22, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28396902/progressive-skeletal-benefits-of-physical-activity-when-young-as-assessed-at-the-midshaft-humerus-in-male-baseball-players
#18
S J Warden, A M Weatherholt, A S Gudeman, D C Mitchell, W R Thompson, R K Fuchs
Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. INTRODUCTION: The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls...
April 10, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28379630/uv-induced-somatic-mutations-elicit-a-functional-t-cell-response-in-the-yummer1-7-mouse-melanoma-model
#19
Jake Wang, Curtis J Perry, Katrina Meeth, Durga Thakral, William Damsky, Goran Micevic, Susan Kaech, Kim Blenman, Marcus Bosenberg
Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These somatic mutations may produce neoantigens that are recognized by the immune system, leading to an antitumor response. By irradiating a parental mouse melanoma cell line carrying three driver mutations with UVB and expanding a single-cell clone, we generated a mutagenized model that exhibits high somatic mutation burden. When inoculated at low cell numbers in immunocompetent C57BL/6J mice, YUMMER1.7 (Yale University Mouse Melanoma Exposed to Radiation) regresses after a brief period of growth...
July 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28378354/ecological-regime-shift-drives-declining-growth-rates-of-sea-turtles-throughout-the-west-atlantic
#20
Karen A Bjorndal, Alan B Bolten, Milani Chaloupka, Vincent S Saba, Cláudio Bellini, Maria A G Marcovaldi, Armando J B Santos, Luis Felipe Wurdig Bortolon, Anne B Meylan, Peter A Meylan, Jennifer Gray, Robert Hardy, Beth Brost, Michael Bresette, Jonathan C Gorham, Stephen Connett, Barbara Van Sciver Crouchley, Mike Dawson, Deborah Hayes, Carlos E Diez, Robert P van Dam, Sue Willis, Mabel Nava, Kristen M Hart, Michael S Cherkiss, Andrew G Crowder, Clayton Pollock, Zandy Hillis-Starr, Fernando A Muñoz Tenería, Roberto Herrera-Pavón, Vanessa Labrada-Martagón, Armando Lorences, Ana Negrete-Philippe, Margaret M Lamont, Allen M Foley, Rhonda Bailey, Raymond R Carthy, Russell Scarpino, Erin McMichael, Jane A Provancha, Annabelle Brooks, Adriana Jardim, Milagros López-Mendilaharsu, Daniel González-Paredes, Andrés Estrades, Alejandro Fallabrino, Gustavo Martínez-Souza, Gabriela M Vélez-Rubio, Ralf H Boulon, Jaime A Collazo, Robert Wershoven, Vicente Guzmán Hernández, Thomas B Stringell, Amdeep Sanghera, Peter B Richardson, Annette C Broderick, Quinton Phillips, Marta Calosso, John A B Claydon, Tasha L Metz, Amanda L Gordon, Andre M Landry, Donna J Shaver, Janice Blumenthal, Lucy Collyer, Brendan J Godley, Andrew McGowan, Matthew J Witt, Cathi L Campbell, Cynthia J Lagueux, Thomas L Bethel, Lory Kenyon
Somatic growth is an integrated, individual-based response to environmental conditions, especially in ectotherms. Growth dynamics of large, mobile animals are particularly useful as bio-indicators of environmental change at regional scales. We assembled growth rate data from throughout the West Atlantic for green turtles, Chelonia mydas, which are long-lived, highly migratory, primarily herbivorous mega-consumers that may migrate over hundreds to thousands of kilometers. Our dataset, the largest ever compiled for sea turtles, has 9690 growth increments from 30 sites from Bermuda to Uruguay from 1973 to 2015...
April 4, 2017: Global Change Biology
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