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Yuet-Kin Leung, Bin Ouyang, Liang Niu, Changchun Xie, Jun Ying, Mario Medvedovic, Aimin Chen, Pal Weihe, Damaskini Valvi, Philippe Grandjean, Shuk-Mei Ho
Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Jayesh Sheth, Gyan Ranjan, Krati Shah, Riddhi Bhavsar, Frenny Sheth
Newer sequencing technologies decipher molecular variations and increase the knowledge of pathogenesis of complex diseases like intellectual disability (ID), affecting 2-3% of the population. We report a novel family with a missense mutation in LINS1 as a cause for non-syndromic ID. Clinical exome sequencing for ID related genes carried out for a male with dysmorphism, mutism, and cognitive delay was uninformative. Subsequently, "pathogenic" and "likely pathogenic" variants associated with other inherited disorders were searched for as secondary findings...
April 2017: American Journal of Medical Genetics. Part A
Ruth Ruiz Esparza-Garrido, Juan Manuel Rodríguez-Corona, Javier Enrique López-Aguilar, Marco Antonio Rodríguez-Florido, Ana Claudia Velázquez-Wong, Rubí Viedma-Rodríguez, Fabio Salamanca-Gómez, Miguel Ángel Velázquez-Flores
Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively...
October 13, 2016: Molecular Neurobiology
Carmella Romeo, Matthew C Weber, Mahsa Zarei, Danielle DeCicco, Saswati N Chand, Angie D Lobo, Jordan M Winter, Janet A Sawicki, Jonathan N Sachs, Nicole Meisner-Kober, Charles J Yeo, Rajanikanth Vadigepalli, Mark L Tykocinski, Jonathan R Brody
UNLABELLED: Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal cancers, in part, due to resistance to both conventional and targeted therapeutics. TRAIL directly induces apoptosis through engagement of cell surface Death Receptors (DR4 and DR5), and has been explored as a molecular target for cancer treatment. Clinical trials with recombinant TRAIL and DR-targeting agents, however, have failed to show overall positive outcomes. Herein, we identify a novel TRAIL resistance mechanism governed by Hu antigen R (HuR, ELAV1), a stress-response protein abundant and functional in PDA cells...
July 2016: Molecular Cancer Research: MCR
C Winkler, A Doller, G Imre, A Badawi, T Schmid, S Schulz, N Steinmeyer, J Pfeilschifter, K Rajalingam, W Eberhardt
Caspase-2 represents the most conserved member of the caspase family, which exhibits features of both initiator and effector caspases. Using ribonucleoprotein (RNP)-immunoprecipitation assay, we identified the proapoptotic caspase-2L encoding mRNA as a novel target of the ubiquitous RNA-binding protein HuR in DLD-1 colon carcinoma cells. Unexpectedly, crosslinking-RNP and RNA probe pull-down experiments revealed that HuR binds exclusively to the caspase-2-5' untranslated region (UTR) despite that the 3' UTR of the mRNA bears several adenylate- and uridylate-rich elements representing the prototypical HuR binding sites...
2014: Cell Death & Disease
Auxane Buresi, Roger P Croll, Stefano Tiozzo, Laure Bonnaud, Sébastien Baratte
Embryonic cuttlefish can first respond to a variety of sensory stimuli during early development in the egg capsule. To examine the neural basis of this ability, we investigated the emergence of sensory structures within the developing epidermis. We show that the skin facing the outer environment (not the skin lining the mantle cavity, for example) is derived from embryonic domains expressing the Sepia officinalis ortholog of pax3/7, a gene involved in epidermis specification in vertebrates. On the head, they are confined to discrete brachial regions referred to as "arm pillars" that expand and cover Sof-pax3/7-negative head ectodermal tissues...
September 1, 2014: Journal of Comparative Neurology
Shruti Lal, Richard A Burkhart, Neil Beeharry, Vikram Bhattacharjee, Eric R Londin, Joseph A Cozzitorto, Carmella Romeo, Masaya Jimbo, Zoë A Norris, Charles J Yeo, Janet A Sawicki, Jordan M Winter, Isidore Rigoutsos, Timothy J Yen, Jonathan R Brody
HuR (ELAV1), an RNA-binding protein abundant in cancer cells, primarily resides in the nucleus, but under specific stress (e.g., gemcitabine), HuR translocates to the cytoplasm in which it tightly modulates the expression of mRNA survival cargo. Here, we demonstrate for the first time that stressing pancreatic ductal adenocarcinoma (PDA) cells by treatment with DNA-damaging anticancer agents (mitomycin C, oxaliplatin, cisplatin, carboplatin, and a PARP inhibitor) results in HuR's translocation from the nucleus to the cytoplasm...
February 15, 2014: Cancer Research
Liqin Yuan, Yuzhong Xiao, Qiuzhi Zhou, Dongmei Yuan, Baiping Wu, Gannong Chen, Jianlin Zhou
The Maelstrom (MAEL) gene is a cancer-testis (or cancer-germline) gene, which is predominantly expressed in germline cells under normal conditions, but is aberrantly expressed in a range of human cancer cells. In germline cells, MAEL is found predominantly in the nuage, where it plays an essential role in piRNA biogenesis and piRNA-mediated silencing of transposons. However, the role of MAEL in cancer has not been elucidated. We performed immunoprecipitation and Nano-LC-MS/MS analysis to investigate the interactome of MAEL, and identified 14 components of stress granules (SGs) as potential binding partners of MAEL in MDA-MB-231 human breast cancer and SW480 colorectal cancer cells...
January 2014: Oncology Reports
Kenneth C Kleene
mRNA-specific regulation of translational activity plays major roles in directing the development of meiotic and haploid spermatogenic cells in mammals. Although many RNA-binding proteins (RBPs) have been implicated in normal translational control and sperm development, little is known about the keystone of the mechanisms: the interactions of RBPs and microRNAs with cis-elements in mRNA targets. The problems in connecting factors and elements with translational control originate in the enormous complexity of post-transcriptional regulation in mammalian cells...
July 2013: Reproduction: the Official Journal of the Society for the Study of Fertility
Auxane Buresi, Ester Canali, Laure Bonnaud, Sébastien Baratte
Among the Lophotrochozoa, centralization of the nervous system reaches an exceptional level of complexity in cephalopods, where the typical molluscan ganglia become highly developed and fuse into hierarchized lobes. It is known that ganglionic primordia initially emerge early and simultaneously during cephalopod embryogenesis but no data exist on the process of neuron differentiation in this group. We searched for members of the elav/hu family in the cuttlefish Sepia officinalis, since they are one of the first genetic markers of postmitotic neural cells...
May 1, 2013: Journal of Comparative Neurology
Nagayasu Nakanishi, Eduard Renfer, Ulrich Technau, Fabian Rentzsch
As a sister group to Bilateria, Cnidaria is important for understanding early nervous system evolution. Here we examine neural development in the anthozoan cnidarian Nematostella vectensis in order to better understand whether similar developmental mechanisms are utilized to establish the strikingly different overall organization of bilaterian and cnidarian nervous systems. We generated a neuron-specific transgenic NvElav1 reporter line of N. vectensis and used it in combination with immunohistochemistry against neuropeptides, in situ hybridization and confocal microscopy to analyze nervous system formation in this cnidarian model organism in detail...
January 2012: Development
Timothy K Williams, Christina L Costantino, Nikolai A Bildzukewicz, Nathan G Richards, David W Rittenhouse, Lisa Einstein, Joseph A Cozzitorto, Judith C Keen, Abhijit Dasgupta, Myriam Gorospe, Gregory E Gonye, Charles J Yeo, Agnieszka K Witkiewicz, Jonathan R Brody
The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity...
2010: PloS One
Mallika Ghosh, Hector Leonardo Aguila, Jason Michaud, Youxi Ai, Ming-Tao Wu, Annabrita Hemmes, Ari Ristimaki, Caiying Guo, Henry Furneaux, Timothy Hla
The RNA-binding protein HuR (also known as ELAV1) binds to the 3'-untranslated region of mRNAs and regulates transcript stability and translation. However, the in vivo functions of HuR are not well understood. Here, we report that murine HuR is essential for life; postnatal global deletion of Elavl1 induced atrophy of hematopoietic organs, extensive loss of intestinal villi, obstructive enterocolitis, and lethality within 10 days. Upon Elavl1 deletion, progenitor cells in the BM, thymus, and intestine underwent apoptosis, whereas quiescent stem cells and differentiated cells were unaffected...
December 2009: Journal of Clinical Investigation
Lauren A Licata, Christine L Hostetter, James Crismale, Anjali Sheth, Judith Clancy Keen
Meta-analyses of microarray data indicate that GATA3 is co-expressed with estrogen receptor alpha (ER) in breast cancer cells. While the significance of this remains unclear, it is thought that GATA3 may serve as a prognostic indicator in breast tumors and may play a role in ER signaling. Recently, reciprocal regulation of GATA3 and ER transcription was demonstrated, suggesting that control of their expression is intertwined. We sought to determine whether GATA3 and ER expression was also coordinately regulated at other levels...
July 2010: Breast Cancer Research and Treatment
Néva P Meyer, Elaine C Seaver
Intertaxonomic comparisons are important for understanding neurogenesis and evolution of nervous systems, but high-resolution, cellular studies of early central nervous system development and the molecular mechanisms controlling this process in lophotrochozoans are still lacking. We provide a detailed cellular and molecular description of early brain neurogenesis in a lophotrochozoan annelid, Capitella sp. I. We utilized different approaches including DiI lineage tracing, immunohistochemistry, BrdU labeling, and gene expression analyses to characterize neural precursor cells in Capitella sp...
November 1, 2009: Developmental Biology
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