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https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#1
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#2
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#3
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445889/genetic-polymorphisms-in-aromatase-cyp19a1-are-not-associated-with-gonadal-phenotypes-in-red-eared-slider-turtle-hatchlings-developed-at-a-pivotal-temperature
#4
Yuiko Matsumoto, David Crews
Embryonic gonad sex in many reptilian species is determined by the incubation temperature of the egg, a differentiation process known as temperature-dependent sex determination (TSD). Incubation at the pivotal temperature (PvT) results in approximately an equal number of offspring of both sexes. We investigated the potential contribution of genetic variations that drives the gonadal differentiation into testes or ovaries under this temperature in the red-eared slider turtle (Trachemys scripta). Four male and 4 female hatchlings of eggs that had been incubated at the PvT were examined for polymorphisms at an approximately 23-kb region of the aromatase (cyp19a1) gene...
April 27, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28445885/patterns-of-microglial-cell-activation-in-alzheimer-disease-and-frontotemporal-lobar-degeneration
#5
Ricardo Taipa, Paulo Brochado, Andrew Robinson, Inês Reis, Patrício Costa, David M Mann, Manuel Melo Pires, Nuno Sousa
AIMS: Microglia-driven neuroinflammation can play an important role in the pathophysiology of neurodegenerative disorders. In this study, we sought to characterize the distribution of microglial cell activation in 2 neurodegenerative dementias with distinct protein signatures, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) of the TDP subtype, and to determine if there was an anatomical correlation with the phenotypes most commonly associated with these conditions...
April 27, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28445878/differential-allelic-expression-of-htr1b-in-suicide-victims-genetic-and-epigenetic-effect-of-the-cis-acting-variants
#6
Ali Bani-Fatemi, Aaron Howe, Clement Zai, James L Kennedy, John Vincent, John Strauss, Albert Wong, Vincenzo De Luca
OBJECTIVES: In the present study, we tested the allelic imbalance of the C861G single nucleotide polymorphism (SNP) of HTR1B in the frontal cortex of suicide victims. METHODS: The study was conducted using 3 sets of samples. First, C861G allele-specific mRNA levels in the frontal cortex were compared between suicide (n = 13) and nonsuicide controls (n = 13) from the Stanley Medical Research postmortem brain collection. Second, we tested common variants in the HTR1B promoter for linkage disequilibrium (LD) with the C861G variant in an unrelated sample of suicide attempters (SA; n = 38) and non-SA (NSA; n = 42)...
April 27, 2017: Neuropsychobiology
https://www.readbyqxmd.com/read/28445851/development-and-validation-of-a-uhplc-esi-ms-ms-method-for-the-simultaneous-quantification-of-mammal-lysophosphatidylcholines-and-lysophosphatidylethanolamines-in-serum
#7
Susana Suárez-García, Lluís Arola, Aïda Pascual-Serrano, Anna Arola-Arnal, Gerard Aragonès, Cinta Bladé, Manuel Suárez
Recent investigations based on non-targeted metabolomics have proposed lysophospholipids (Lyso-PLs) as biomarkers of different diseases. In particular, lysophosphatidylcholines (Lyso-PCs) and lysophosphatidylethanolamines (Lyso-PEs) have been associated with serious lipid pathologies. Methods to determine the different molecular species in a biological sample and to quantify even less abundant species are required for the evaluation of the Lyso-PL pattern as a novel comprehensive biomarker of dyslipidemia. This study describes the development and validation of an ultra-high-performance liquid chromatography coupled to tandem mass spectrometry assay for the determination of a large number of Lyso-PCs and Lyso-PEs in biological samples...
April 18, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28445809/inhibition-of-14q32-microrna-mir-495-reduces-lesion-formation-intimal-hyperplasia-and-plasma-cholesterol-levels-in-experimental-restenosis
#8
Sabine M J Welten, Rob C M de Jong, Anouk Wezel, Margreet R de Vries, Martin C Boonstra, Laura Parma, J Wouter Jukema, Tetje C van der Sluis, Ramon Arens, Ilze Bot, Sudhir Agrawal, Paul H A Quax, A Yaël Nossent
BACKGROUND AND AIMS: We aimed at investigating the role of 14q32 microRNAs in intimal hyperplasia and accelerated atherosclerosis; two major contributors to restenosis. Restenosis occurs regularly in patients treated for coronary artery disease and peripheral arterial disease. We have previously shown that inhibition of 14q32 microRNAs leads to increased post-ischemic neovascularization, and microRNA miR-494 also decreased atherosclerosis, while increasing plaque stability. We hypothesized that 14q32 microRNA inhibition has beneficial effects on intimal hyperplasia, as well as accelerated atherosclerosis...
April 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28445787/adipose-derived-stem-cells-were-impaired-in-restricting-cd4-t-cell-proliferation-and-polarization-in-type-2-diabetic-apoe-mouse
#9
Ming-Hao Liu, Ya Li, Lu Han, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Hui-Min Zhou, Ming Song, Yi-Hui Li, Meng-Xiong Tang, Wei Zhang, Ming Zhong
BACKGROUND: Atherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4(+)T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4(+)T cells as well...
April 23, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#10
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445733/nf-%C3%AE%C2%BAb-immunity-in-the-brain-determines-fly-lifespan-in-healthy-aging-and-age-related-neurodegeneration
#11
Ilias Kounatidis, Stanislava Chtarbanova, Yang Cao, Margaret Hayne, Dhruv Jayanth, Barry Ganetzky, Petros Ligoxygakis
During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445723/mosquitoes-transmit-unique-west-nile-virus-populations-during-each-feeding-episode
#12
Nathan D Grubaugh, Joseph R Fauver, Claudia Rückert, James Weger-Lucarelli, Selene Garcia-Luna, Reyes A Murrieta, Alex Gendernalik, Darci R Smith, Doug E Brackney, Gregory D Ebel
Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445722/genomic-analyses-reveal-the-influence-of-geographic-origin-migration-and-hybridization-on-modern-dog-breed-development
#13
Heidi G Parker, Dayna L Dreger, Maud Rimbault, Brian W Davis, Alexandra B Mullen, Gretchen Carpintero-Ramirez, Elaine A Ostrander
There are nearly 400 modern domestic dog breeds with a unique histories and genetic profiles. To track the genetic signatures of breed development, we have assembled the most diverse dataset of dog breeds, reflecting their extensive phenotypic variation and heritage. Combining genetic distance, migration, and genome-wide haplotype sharing analyses, we uncover geographic patterns of development and independent origins of common traits. Our analyses reveal the hybrid history of breeds and elucidate the effects of immigration, revealing for the first time a suggestion of New World dog within some modern breeds...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445719/kat-independent-gene-regulation-by-tip60-promotes-esc-self-renewal-but-not-pluripotency
#14
Diwash Acharya, Sarah J Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A Rivera-Pérez, Thomas G Fazzio
Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445693/high-content-analysis-screening-for-cell-cycle-regulators-using-arrayed-synthetic-crrna-libraries
#15
Žaklina Strezoska, Matthew R Perkett, Eldon T Chou, Elena Maksimova, Emily M Anderson, Shawn McClelland, Melissa L Kelley, Annaleen Vermeulen, Anja van Brabant Smith
The CRISPR-Cas9 system has been utilized for large-scale, loss-of-function screens mainly using lentiviral pooled formats and cell-survival phenotypic assays. Screening in an arrayed format expands the types of phenotypic readouts that can be used to now include high-content, morphology-based assays, and with the recent availability of synthetic crRNA libraries, new studies are emerging. Here, we use a cell cycle reporter cell line to perform an arrayed, synthetic crRNA:tracrRNA screen targeting 169 genes (> 600 crRNAs) and used high content analysis (HCA) to identify genes that regulate the cell cycle...
April 23, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28445677/overexpression-of-the-cytokine-baff-and-autoimmunity-risk
#16
Maristella Steri, Valeria Orrù, M Laura Idda, Maristella Pitzalis, Mauro Pala, Ilenia Zara, Carlo Sidore, Valeria Faà, Matteo Floris, Manila Deiana, Isadora Asunis, Eleonora Porcu, Antonella Mulas, Maria G Piras, Monia Lobina, Sandra Lai, Mara Marongiu, Valentina Serra, Michele Marongiu, Gabriella Sole, Fabio Busonero, Andrea Maschio, Roberto Cusano, Gianmauro Cuccuru, Francesca Deidda, Fausto Poddie, Gabriele Farina, Mariano Dei, Francesca Virdis, Stefania Olla, Maria A Satta, Mario Pani, Alessandro Delitala, Eleonora Cocco, Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Paola Ferrigno, Maria Ban, Nadia Barizzone, Maurizio Leone, Franca R Guerini, Matteo Piga, Davide Firinu, Ingrid Kockum, Izaura Lima Bomfim, Tomas Olsson, Lars Alfredsson, Ana Suarez, Patricia E Carreira, Maria J Castillo-Palma, Joseph H Marcus, Mauro Congia, Andrea Angius, Maurizio Melis, Antonio Gonzalez, Marta E Alarcón Riquelme, Berta M da Silva, Maurizio Marchini, Maria G Danieli, Stefano Del Giacco, Alessandro Mathieu, Antonello Pani, Stephen B Montgomery, Giulio Rosati, Jan Hillert, Stephen Sawcer, Sandra D'Alfonso, John A Todd, John Novembre, Gonçalo R Abecasis, Michael B Whalen, Maria G Marrosu, Alessandra Meloni, Serena Sanna, Myriam Gorospe, David Schlessinger, Edoardo Fiorillo, Magdalena Zoledziewska, Francesco Cucca
Background Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Methods Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE)...
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28445652/identification-of-quantitative-trait-loci-underlying-seed-protein-content-of-soybean-including-main-epistatic-and-qtl-%C3%A3-environment-effects-in-different-regions-of-northeast-china
#17
Weili Teng, Wen Li, Q I Zhang, Depeng Wu, Xue Zhao, Haiyan Li, Yingpeng Han, Wenbin Li
The objective here was to identify QTL, their epistatic effects and QTLs x environments interaction underlying soybean protein content (PC). The mapping population, consisted of 129 recombinant inbred lines (RILs), was created by crossing 'Dongnong46' and 'L-100'. Phenotypic data of the parents and RILs were collected for four years in three locations of Heilongjiang Province of China. A total of 213 simple sequence repeat markers were used to construct a genetic linkage map. Eight QTLs, located on seven chromosomes (Chr), were identified to be associated with PC among the ten tested environments...
April 26, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28445628/characterization-of-four-latin-american-families-confirms-previous-findings-and-reveals-novel-features-of-acid-labile-subunit-als-deficiency
#18
Paula A Scaglia, Ana C Keselman, Débora Braslavsky, Lucía C Martucci, Liliana M Karabatas, Sabina Domené, Mariana L Gutiérrez, María G Ballerini, María G Ropelato, Angela Spinola-Castro, Adriana A Siviero-Miachon, Juliana Saito Tartuci, Sol Rodríguez Azrak, Rodolfo A Rey, Héctor G Jasper, Ignacio Bergadá, Horacio M Domené
OBJECTIVE: ALS deficiency (ACLSD), caused by inactivating mutations in both IGFALS gene alleles, is characterized by marked reduction of IGF-I and IGFBP-3 levels associated to mild growth retardation. The aim of this study was to expand the known phenotype and genetic characteristics of ACLSD by reporting data from four index cases and their families. DESIGN: Auxological data, biochemical and genetic studies were performed in four children diagnosed with ACLSD and all available relatives...
April 26, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28445609/exosomes-derived-from-mesenchymal-non-small-cell-lung-cancer-cells-promote-chemoresistance
#19
Richard J Lobb, Rosa van Amerongen, Adrian Wiegmans, Sunyoung Ham, Jill E Larsen, Andreas Möller
Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the most common cause of mortality in lung cancer patients. NSCLC is often associated with resistance to chemotherapeutics and together with rapid metastatic spread, results in limited, mostly palliative, treatment options and poor patient survival. NSCLC are heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal NSCLC cells are thought to be responsible for the chemoresistance phenotype, but if and how this phenotype can be transferred to other NSCLC cells is currently not known...
April 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28445605/high-throughput-cell-mechanical-phenotyping-for-label-free-titration-assays-of-cytoskeletal-modifications
#20
Stefan Golfier, Philipp Rosendahl, Alexander Mietke, Maik Herbig, Jochen Guck, Oliver Otto
The mechanical fingerprint of cells is inherently linked to the structure of the cytoskeleton and can serve as a label free marker for cell homeostasis or pathologic states. How cytoskeletal composition affects the physical response of cells to external loads has been intensively studied with a spectrum of techniques, yet quantitative and statistically powerful investigations in the form of titration assays are hampered by the low throughput of most available methods. In this study, we employ real-time deformability cytometry (RT-DC), a novel microfluidic tool to examine the effects of biochemically modified F-actin and microtubule stability and nuclear chromatin structure on cell deformation in a human leukemia cell line (HL60)...
April 26, 2017: Cytoskeleton
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