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Balachandar Radhakrishnan, A Alwin Prem Anand
MicroRNAs (miRNAs) are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9) is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon), midbrain, hindbrain, and spinal cord of vertebrate species is highlighted...
2016: Journal of Experimental Neuroscience
Martyna Bieniek-Kobuszewska, Grzegorz Panasiewicz, Aleksandra Lipka, Marta Majewska, Bozena Szafranska
This is a pioneer study of single nucleotide polymorphisms (SNPs) within the entire promoter region (1204 bp) of the dominant pPAG2-L subfamily in the pig. The pPAG2-L subfamily was sequenced/examined using genomic deoxyribonucleic acid (gDNA) templates of crossbreed pigs (Landrace x Large White), and compared to two bacterial artificial chromosome (BAC) clones containing gDNA of the Duroc breed (as the positive controls). Our analysis of the pPAG2-L promoter identified 31 SNPs and one InDel mutation in crossbreed pigs...
October 5, 2016: Functional & Integrative Genomics
Duncan M Gascoyne, Alison H Banham
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of mature B-cell lymphoma. While the majority of patients are cured with immunochemotherapy incorporating the anti-CD20 monoclonal antibody rituximab (R-CHOP), relapsed and refractory patients still have a dismal prognosis. DLBCL subtypes including an aggressive activated B-cell-like (ABC) and a more favorable prognosis germinal center-like (GCB) DLBCL have been identified by gene expression profiling and are characterized by distinct genetic abnormalities and oncogenic pathways...
September 27, 2016: Leukemia & Lymphoma
Xin Wang, Ji Sun, Meiling Cui, Fangyu Zhao, Chao Ge, Taoyang Chen, Ming Yao, Jinjun Li
Forkhead box P1 (FOXP1) belongs to a family of winged-helix transcription factors that are involved in the processes of cellular proliferation, differentiation, metabolism, and longevity. FOXP1 can affect cell proliferation and migratory ability in hepatocellular carcinoma (HCC) in vitro. However, little is known about the mechanism of FOXP1 in the proliferation of HCC cells. This study aimed to further explore the function of FOXP1 on the proliferation of HCC cells as well as the relevant mechanism involved...
2016: International Journal of Molecular Sciences
Andrew Bakshi, Zhihong Zhu, Anna A E Vinkhuyzen, W David Hill, Allan F McRae, Peter M Visscher, Jian Yang
We propose a method (fastBAT) that performs a fast set-based association analysis for human complex traits using summary-level data from genome-wide association studies (GWAS) and linkage disequilibrium (LD) data from a reference sample with individual-level genotypes. We demonstrate using simulations and analyses of real datasets that fastBAT is more accurate and orders of magnitude faster than the prevailing methods. Using fastBAT, we analyze summary data from the latest meta-analyses of GWAS on 150,064-339,224 individuals for height, body mass index (BMI), and schizophrenia...
2016: Scientific Reports
Jonathan Bond, Renae Domaschenz, Mónica Roman-Trufero, Pierangela Sabbattini, Isabel Ferreiros-Vidal, Gareth Gerrard, Vahid Asnafi, Elizabeth Macintyre, Matthias Merkenschlager, Niall Dillon
Ikaros and Foxp1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies. We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL). We also identify the Gpr132 gene, which encodes the orphan G protein-coupled receptor G2A, as a novel target for Foxp1...
August 30, 2016: Oncotarget
Claire Palles, John M Findlay, Ian Tomlinson
Eight loci have been identified by the two genome-wide association studies of Barrett's esophagus that have been conducted to date. Esophageal adenocarcinoma cases were included in the second study following evidence that predisposing genetic variants for this cancer overlap with those for Barrett's esophagus. Genes with roles in embryonic development of the foregut are adjacent to 6 of the loci identified (FOXF1, BARX1, FOXP1, GDF7, TBX5, and ALDH1A2). An additional locus maps to a gene with known oncogenic potential (CREB-regulated transcription coactivator 1), but expression quantitative trait data implicates yet another gene involved in esophageal development (PBX4)...
2016: Advances in Experimental Medicine and Biology
Ruth Morona, José Luis Eduardo Ferran, Luis Puelles, Agustín González
Our previous analysis of progenitor domains in the pretectum of Xenopus revealed three molecularly distinct anteroposterior subdivisions identified as precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic domains (Morona et al. [2011] J Comp Neurol 519:1024-1050). Here we analyzed at later developmental stages the nuclei derived from these areas, attending to their gene expression patterns and histogenesis. Transcription-factor gene markers were used to selectively map derivatives of each domain: Pax7 and Pax6 (CoP); Foxp1 and Six3 (JcP); and Xiro1, VGlut2, Ebf1, and Ebf3 (PcP)...
August 19, 2016: Journal of Comparative Neurology
Deniz Cizmeci, Emma L Dempster, Olivia L Champion, Sariqa Wagley, Ozgur E Akman, Joann L Prior, Orkun S Soyer, Jonathan Mill, Richard W Titball
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling...
2016: Scientific Reports
Jian Xiao, Bixiu He, Yong Zou, Xi Chen, Xiaoxiao Lu, Mingxuan Xie, Wei Li, Shuya He, Shaojin You, Qiong Chen
The prognostic value of forkhead box protein P1 (FOXP1) protein expression in tumors remains controversial. Therefore, we conducted a systematic review and meta-analysis, searching the PubMed, Embase and Web of Science databases to identify eligible studies. In total, we analyzed 22 articles that examined 9 tumor types and included 2468 patients. Overall, decreased expression of FOXP1 protein was associated with favorable overall survival (OS) in lymphoma patients (HR = 0.38, 95%CI: 0.30-0.48, p < 0...
2016: Scientific Reports
Makito Mizunuma, Yoshihito Yokoyama, Masayuki Futagami, Kayo Horie, Jun Watanabe, Hideki Mizunuma
Endometrial cancers are mostly estrogen-dependent. FOXP1 is a P subfamily of forkhead box (FOX), and known as an estrogen-responsive transcription factor. The aims of this study were to examine histological location of FOXP1 in normal and malignant endometrium, and to investigate a possible association between FOXP1 and other factors considered to be involved in pathogenesis of endometrial cancer. The levels of FOXP1, estrogen receptor (ER)α, and ERβ expression were examined immunohistochemically in normal and malignant endometrium obtained from 75 women (8 normal, 8 atypical endometrial hyperplasia, and 59 endometrial cancers from grade 1 to 3)...
May 2016: Heliyon
S O Vozianov, V I Kashuba, V M Grygorenko, V V Gordiyuk, R O Danylets, Yu M Bondarenko, M V Vikarchuk
The biopsy material specimens were investigated in 33 patients, examined for the prostatic cancer suspicion. In accordance to the morphological investigation data, in 15 patients a benign prostatic hyperplasia was verified, and in 18--pancreatic adenocarcinoma. NotI-Microchips of 180 clones of the third chromosome were used for determination of epigenetic changes. In 50 genes of the third chromosome a high rate of the methylation state changes (from 33 to 82%) was noted. Some changed genes take part in cancerogenesis (HMGB1L5, LRRC58, GPR149, DZIP1L, C3orf77, NUDT16) and in the prostatic gland cancer occurrence (BCL6, ITGA9, FBLN2, SOX2, LRRC3B etc...
April 2016: Klinichna Khirurhiia
L M Saleh, W Wang, S E M Herman, N S Saba, V Anastas, E Barber, M Corrigan-Cummins, M Farooqui, C Sun, S M Sarasua, Z Zhao, N K Abousamra, O Elbaz, H A Abdelghaffar, A Wiestner, K R Calvo
The lymph node (LN) is the site of chronic lymphocytic leukemia (CLL) cell activation and proliferation. Aberrant microRNA (miRNA) expression has been shown to have a role in CLL pathogenesis; however, a comparison of miRNA expression between CLL cells in the LN and the peripheral blood (PB) has previously not been reported. On the basis of the analysis of 17 paired LN and PB samples from CLL patients, we identify a panel of miRNAs that are increased in LN CLL cells correlating with an activation phenotype...
July 19, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
M Ozgur Taskapilioglu, Deniz Billur, Sule Kizil, Ozlem Taskapilioglu, Gokhan Ocakoglu, Sevim Aydin, Ahmet Bekar, Agahan Unlu
AIM: To demonstrate the effect of glatiramer acetate (GA) in chick embryos on neural tube (NT) development, and to explore its effects of Foxp1, apoptosis, and N-cadherin. MATERIAL AND METHODS: One hundred fertile, specific pathogen free eggs were divided into 5 groups for this study. The eggshell was windowed specifically at 24 hours of incubation. The embryos in Group 1 (n=20) were treated with 10 μl physiological saline; in Group 2 the embryos (n=20) were given 10 μl GA (equal to daily human therapeutic dose); 20 μl GA (equal to twice daily human therapeutic dose) was injected to embryos in Group 3 (n=20); in Group 4 and 5, 30 μl and 40 μl GA were administered to the embryos (n=20) (equal to x3 and x4 daily human therapeutic dose, respectively)...
2016: Turkish Neurosurgery
Elena Garcia-Calero, Salvador Martinez
Different bird orders show diversity in neural capabilities supported by variations in brain morphology. The parahippocampal domain in the medial pallium, together with the hippocampus proper, plays an important role in memory skills. In the present work, we analyze the expression pattern of the FoxP1 protein in the parahippocampal area of four different bird species: the nonvocal learner birds quail and chicken (Galliformes) and two vocal learner birds, i.e. the zebra finch (Passeriformes) and the budgerigar (Psittaciformes), at different developmental and adult stages...
2016: Brain, Behavior and Evolution
Jessica Lauriol, Janel R Cabrera, Ashbeel Roy, Kimberly Keith, Sara M Hough, Federico Damilano, Bonnie Wang, Gabriel C Segarra, Meaghan E Flessa, Lauren E Miller, Saumya Das, Roderick Bronson, Kyu-Ho Lee, Maria I Kontaridis
Hypertrophic cardiomyopathy is a common cause of mortality in congenital heart disease (CHD). Many gene abnormalities are associated with cardiac hypertrophy, but their function in cardiac development is not well understood. Loss-of-function mutations in PTPN11, which encodes the protein tyrosine phosphatase (PTP) SHP2, are implicated in CHD and cause Noonan syndrome with multiple lentigines (NSML), a condition that often presents with cardiac hypertrophic defects. Here, we found that NSML-associated hypertrophy stems from aberrant signaling mechanisms originating in developing endocardium...
August 1, 2016: Journal of Clinical Investigation
Shanru Li, Michael Morley, MinMin Lu, Su Zhou, Kathleen Stewart, Catherine A French, Haley O Tucker, Simon E Fisher, Edward E Morrisey
The inhibitory mechanisms that prevent gene expression programs from one tissue to be expressed in another are poorly understood. Foxp1/2/4 are forkhead transcription factors that repress gene expression and are individually important for endoderm development. We show that combined loss of all three Foxp1/2/4 family members in the developing anterior foregut endoderm leads to a loss of lung endoderm lineage commitment and subsequent development. Foxp1/2/4 deficient lungs express high levels of transcriptional regulators not normally expressed in the developing lung, including Pax2, Pax8, Pax9 and the Hoxa9-13 cluster...
August 15, 2016: Developmental Biology
Hong Hanh Nguyen, Therasa Kim, Sang Yun Song, Somang Park, Hyang Hee Cho, Sung-Hoon Jung, Jae-Sook Ahn, Hyeoung-Joon Kim, Je-Jung Lee, Hee-Ok Kim, Jae-Ho Cho, Deok-Hwan Yang
Despite of the potential implications for cancer immunotherapy, conventional approaches using in vitro expanded CD8(+) T cells have suboptimal outcomes, mostly due to loss of functionality from cellular exhaustion. We therefore investigated the phenotypic and functional differences among in vitro activated CD8(+) T cells of three different sources, namely naïve (NTeff), memory (MTeff) and tumor-infiltrating lymphocytes (TILeff) from human and mice, to better understand mechanisms behind potent effector functions and potential for overcoming current limitations...
2016: Scientific Reports
Exequiel Medina, Cristóbal Córdova, Pablo Villalobos, Javiera Reyes, Elizabeth A Komives, César A Ramírez-Sarmiento, Jorge Babul
The forkhead family of transcription factors (Fox) controls gene transcription during key processes such as regulation of metabolism, embryogenesis, and immunity. Structurally, Fox proteins feature a conserved DNA-binding domain known as forkhead. Interestingly, solved forkhead structures of members from the P subfamily (FoxP) show that they can oligomerize by three-dimensional domain swapping, whereby structural elements are exchanged between adjacent subunits, leading to an intertwined dimer. Recent evidence has largely stressed the biological relevance of domain swapping in FoxP, as several disease-causing mutations have been related to impairment of this process...
June 7, 2016: Biophysical Journal
Kah Keng Wong, Duncan M Gascoyne, Elizabeth J Soilleux, Linden Lyne, Hayley Spearman, Giovanna Roncador, Lars M Pedersen, Michael B Møller, Tina M Green, Alison H Banham
FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL...
May 20, 2016: Oncotarget
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