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https://www.readbyqxmd.com/read/27930301/reprogramming-cell-fate-with-a-genome-scale-library-of-artificial-transcription-factors
#1
Asuka Eguchi, Matthew J Wleklinski, Mackenzie C Spurgat, Evan A Heiderscheit, Anna S Kropornicka, Catherine K Vu, Devesh Bhimsaria, Scott A Swanson, Ron Stewart, Parameswaran Ramanathan, Timothy J Kamp, Igor Slukvin, James A Thomson, James R Dutton, Aseem Z Ansari
Artificial transcription factors (ATFs) are precision-tailored molecules designed to bind DNA and regulate transcription in a preprogrammed manner. Libraries of ATFs enable the high-throughput screening of gene networks that trigger cell fate decisions or phenotypic changes. We developed a genome-scale library of ATFs that display an engineered interaction domain (ID) to enable cooperative assembly and synergistic gene expression at targeted sites. We used this ATF library to screen for key regulators of the pluripotency network and discovered three combinations of ATFs capable of inducing pluripotency without exogenous expression of Oct4 (POU domain, class 5, TF 1)...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#2
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek Clements, Youra Kim, Patrick W K Lee, Shashi Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#3
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27919897/genetic-evidence-for-cytochrome-b-qi-site-inhibition-by-4-1h-quinolone-3-diarylethers-and-antimycin-in-toxoplasma-gondii
#4
P Holland Alday, Igor Bruzual, Aaron Nilsen, Sovitj Pou, Rolf Winter, Choukri Ben Mamoun, Michael K Riscoe, J Stone Doggett
Toxoplasma gondii is an apicomplexan parasite that causes fatal and debilitating brain and eye disease. Endochin-like-quinolones (ELQs) are preclinical compounds that are efficacious against apicomplexan-caused diseases including toxoplasmosis, malaria and babesiosis. Of the ELQs, ELQ-316 has demonstrated the greatest efficacy against acute and chronic experimental toxoplasmosis. Although genetic analyses in other organisms have highlighted the importance of the cytochrome bc1 complex Qi site for ELQ sensitivity, the mechanism of action of ELQs against T...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27915232/quantitative-profiling-of-selective-sox-pou-pairing-on-hundreds-of-sequences-in-parallel-by-coop-seq
#5
Yiming K Chang, Yogesh Srivastava, Caizhen Hu, Adam Joyce, Xiaoxiao Yang, Zheng Zuo, James J Havranek, Gary D Stormo, Ralf Jauch
Cooperative binding of transcription factors is known to be important in the regulation of gene expression programs conferring cellular identities. However, current methods to measure cooperativity parameters have been laborious and therefore limited to studying only a few sequence variants at a time. We developed Coop-seq (cooperativity by sequencing) that is capable of efficiently and accurately determining the cooperativity parameters for hundreds of different DNA sequences in a single experiment. We apply Coop-seq to 12 dimer pairs from the Sox and POU families of transcription factors using 324 unique sequences with changed half-site orientation, altered spacing and discrete randomization within the binding elements...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27909559/identification-of-dietary-patterns-in-urban-population-of-argentina-study-on-diet-obesity-relation-in-population-based-prevalence-study
#6
Sonia Alejandra Pou, María Del Pilar Díaz, Ana Gabriela De La Quintana, Carla Antonella Forte, Laura Rosana Aballay
BACKGROUND/OBJECTIVES: In Argentina, obesity prevalence rose from 14.6% in 2005 to 20.8% in 2013. Although the number of studies on noncommunicable diseases and dietary patterns as a unique dietary exposure measure has increased, information on this topic remains scarce in developing countries. This is the first population-based study investigating the association between diet and obesity using a dietary pattern approach in Argentina. We aimed (a) to identify current dietary patterns of the population of Córdoba city, (b) to investigate its association with obesity prevalence, and (c) to identify and describe dietary patterns from the subgroup of people with obesity...
December 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27895270/dicrocoelium-dendriticum-an-unusual-parasitological-diagnosis-in-a-reference-international-health-unit
#7
Zaira Moure, Francesc Zarzuela, Mateu Espasa, Diana Pou, Nuria Serre-Delcor, Begoña Treviño, Cristina Bocanegra, Israel Molina, Tomas Pumarola, Elena Sulleiro
Finding Dicrocoelium dendriticum eggs in human feces is exceptional and there are few prevalence data available. True infection occurs after accidental ingestion of ants containing metacercariae and spurious infection through the consumption of infected animal liver. Differential diagnosis between true and pseudo-infections is performed through stool examination after a diet free of liver. In addition, microscopy can help to differentiate the type of infection. We report six cases, all from sub-Saharan Africa, detection of this fluke at the Tropical Medicine Unit Vall d'Hebron-Drassanes (Barcelona, Spain)...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27885216/a-novel-heterozygous-intronic-mutation-in-pou1f1-is-associated-with-combined-pituitary-hormone-deficiency
#8
Masaki Takagi, Hotaka Kamasaki, Hiroko Yagi, Ryuji Fukuzawa, Satoshi Narumi, Tomonobu Hasegawa
POU class 1 homeobox 1 (POU1F1) regulates pituitary cell-specific gene expression of somatotropes, lactotropes, and thyrotropes. In humans, two POU1F1 isoforms (long and short isoform), which are generated by the alternative use of the splice acceptor site for exon 2, have been identified. To date, more than 30 POU1F1 mutations in patients with combined pituitary hormone deficiency (CPHD) have been described. All POU1F1 variants reported to date affect both the short and long isoforms of the POU1F1 protein; therefore, it is unclear at present whether a decrease in the function of only one of these two isoforms is sufficient for disease onset in humans...
November 22, 2016: Endocrine Journal
https://www.readbyqxmd.com/read/27863625/facial-nerve-stimulation-following-cochlear-implantation-for-x-linked-stapes-gusher-syndrome-leading-to-identification-of-a-novel-pou3f4-mutation
#9
Jacob L Wester, Catherine Merna, Kevin A Peng, Rebecca Lewis, Ali R Sepahdari, Gail Ishiyama, Kumiko Hosokawa, Kozo Kumakawa, Akira Ishiyama
We report a case of a nine-year-old male who presented with facial nerve stimulation four years after cochlear implantation. Computed tomography was performed revealing a dilated internal auditory meatus and the cochlear implant electrode was found to be protruding into the fallopian canal at the level of the geniculate ganglion. Subsequent genetic analysis demonstrated X-linked deafness type 2 (DFNX2) caused by a novel c.769C > T nucleotide change in the POU domain, class 3, transcription factor 4 gene (POU3F4)...
December 2016: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/27847552/schisandrin-b-a-double-edged-sword-in-nonalcoholic-fatty-liver-disease
#10
REVIEW
Pou Kuan Leong, Kam Ming Ko
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27832276/topical-treatment-with-bromfenac-reduces-retinal-gliosis-and-inflammation-after-optic-nerve-crush
#11
Giuseppe Rovere, Francisco M Nadal-Nicolás, Paloma Sobrado-Calvo, David García-Bernal, Maria Paz Villegas-Pérez, Manuel Vidal-Sanz, Marta Agudo-Barriuso
Purpose: To study the effect of topical administration of bromfenac, a nonsteroidal anti-inflammatory drug (NSAID), on retinal gliosis and levels of prostaglandin E2 (PGE2) after complete optic nerve crush (ONC). Methods: Adult albino rats were divided into the following groups (n = 8 retinas/group): (1) intact, (2) intact and bromfenac treatment (twice a day during 7 days), (3) ONC (7 days), and (4) ONC (7 days) + bromfenac treatment (twice a day during 7 days)...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27810169/conservatism-and-variability-of-gene-expression-profiles-among-homeologous-transcription-factors-in-xenopus-laevis
#12
Minoru Watanabe, Yuuri Yasuoka, Shuuji Mawaribuchi, Aya Kuretani, Michihiko Ito, Mariko Kondo, Haruki Ochi, Hajime Ogino, Akimasa Fukui, Masanori Taira, Tsutomu Kinoshita
Xenopus laevis has an allotetraploid genome of 3.1Gb, in contrast to the diploid genome of a closely related species, Xenopus tropicalis. Here, we identified 412 genes (189 homeolog pairs, one homeologous gene cluster pair, and 28 singletons) encoding transcription factors (TFs) in the X. laevis genome by comparing them with their orthologs from X. tropicalis. Those genes include the homeobox gene family (Mix/Bix, Lhx, Nkx, Paired, POU, and Vent), Sox, Fox, Pax, Dmrt, Hes, GATA, T-box, and some clock genes...
October 31, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27809766/diversity-of-human-and-mouse-homeobox-gene-expression-in-development-and-adult-tissues
#13
Thomas L Dunwell, Peter W H Holland
BACKGROUND: Homeobox genes encode a diverse set of transcription factors implicated in a vast range of biological processes including, but not limited to, embryonic cell fate specification and patterning. Although numerous studies report expression of particular sets of homeobox genes, a systematic analysis of the tissue specificity of homeobox genes is lacking. RESULTS: Here we analyse publicly-available transcriptome data from human and mouse developmental stages, and adult human tissues, to identify groups of homeobox genes with similar expression patterns...
November 3, 2016: BMC Developmental Biology
https://www.readbyqxmd.com/read/27798557/over-expression-of-pou-class-1-homeobox-1-transcription-factor-pit-1-predicts-poor-prognosis-for-breast-cancer-patients
#14
Zhongcheng Gao, Kecheng Xue, Lianfang Zhang, Meng Wei
BACKGROUND: The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) was reported to be associated with tumor progression and metastasis. The purpose of this study was to evaluate the prognostic value of Pit-1 in breast cancer patients. MATERIAL AND METHODS: The relative expression levels of Pit-1 in breast cancer patients were detected by quantitative real-time PCR (qRT-PCR). Chi-square analysis was used to analyze the association between Pit-1 expression and clinical features...
October 31, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27755472/physical-activity-to-overcome-the-adversity-of-widowhood-benefits-beyond-physical-health
#15
Chu-Shiu Li, June Han Lee, Chwen-Chi Liu, Yan-Lan Chan, Christopher Wen, Mu-Lin Chiu, Min Kuang Tsai, Shan Pou Tsai, Jackson Pui Man Wai, Chwen Keng Tsao, Xifeng Wu, Chi Pang Wen
Widowhood has been increasingly encountered because of increasing longevity of women, often characterized by social stigmatization and poor physical and mental health. However, applied research to overcome its adversity has been quite limited. The goal of this study is to explore the role of physical activity in improving the health of widows.A cohort of 446,582 adults in Taiwan who successively participated in a comprehensive medical screening program starting in 1994, including 232,788 women, was followed up for mortality until 2008...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27727398/down-regulation-of-rna-3-terminal-phosphate-cyclase-attenuates-toll-like-receptor-3-mediated-axonal-loss-in-the-retina-and-optic-nerve
#16
Shravan K Chintala, Naveena Daram
Purpose: To investigate the role of RNA 3'-terminal phosphate cyclase (Rtca) in Toll-like receptor 3 (TLR3)-mediated loss of retinal ganglion cells (RGCs) and their axons. Methods: Polyinosinic-polycytidylic acid (Poly[I:C]) or PBS was injected into the vitreous humor of C57BL/6J and Tlr3 knockout mice. C57BL/6J mouse eyes were treated with Rtca silencing RNA or control RNA, with or without PBS or Poly(I:C). At 24, 48, and 72 hours after treatments, RGC loss was determined with the brain-specific homeobox/POU domain protein 3a antibody, and axonal loss was assessed by using the neuronal class III beta-tubulin (Tuj1) antibody...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27722743/purely-substitutional-nitrogen-on-graphene-pt-111-unveiled-by-stm-and-first-principles-calculations
#17
Ana Martín-Recio, Carlos Romero-Muñiz, Pablo Pou, Rubén Pérez, José M Gómez-Rodríguez
Nitrogen doping of graphene can be an efficient way of tuning its pristine electronic properties. Several techniques have been used to introduce nitrogen atoms on graphene layers. The main problem in most of them is the formation of a variety of C-N species that produce different electronic and structural changes on the 2D layer. Here we report on a method to obtain purely substitutional nitrogen on graphene on Pt(111) surfaces. A detailed experimental study performed in situ, under ultra-high vacuum conditions with scanning tunneling microscopy (STM), low energy electron diffraction (LEED) and Auger electron spectroscopy (AES) of the different steps on the preparation of the sample, has allowed us to gain insight into the optimal parameters for this growth method, that combines ion bombardment and annealing...
October 14, 2016: Nanoscale
https://www.readbyqxmd.com/read/27710797/arsenic-removal-by-discontinuous-zvi-two-steps-system-for-drinking-water-production-at-household-scale
#18
Barbara Casentini, Fabiano Teo Falcione, Stefano Amalfitano, Stefano Fazi, Simona Rossetti
Different countries in Europe still suffer of elevated arsenic (As) concentration in groundwaters used for human consumption. In the case of households not connected to the distribution system, decentralized water supply systems, such as Point of Use (POU) and Point of Entry (POE), offer a direct benefit for the consumers. Field scale ex-situ treatment systems based on metallic iron (ZVI) are already available for the production of reduced volumes of drinking water in remote areas (village scale). To address drinking water needs at larger scale, we designed a pilot unit able to produce an elevated daily volume of water for human consumption...
September 28, 2016: Water Research
https://www.readbyqxmd.com/read/27692109/age-related-injury-patterns-in-spanish-trauma-icu-patients-results-from-the-retrauci
#19
Juan Antonio Llompart-Pou, Mario Chico-Fernández, Marcelino Sánchez-Casado, Fermín Alberdi-Odriozola, Francisco Guerrero-López, María Dolores Mayor-García, Javier González-Robledo, María Ángeles Ballesteros-Sanz, Rubén Herrán-Monge, Rafael León-López, Lucía López-Amor, Ana Bueno-González
BACKGROUND: Injury patterns may differ in trauma patients when age is considered. This information is relevant in the management of trauma patients and for planning preventive measures. METHODS: We included in the study all patients admitted for traumatic disease in the participating ICUs from November 23(rd), 2012 to July 31(st), 2015 with complete records. Data on epidemiology, injury patterns, severity scores, acute management, resources utilisation and outcome were recorded and compared in the following groups of age: ≤55years (young adults), 56-65 years (adults), 66-75 years (elderly), >75years (very elderly)...
September 2016: Injury
https://www.readbyqxmd.com/read/27671160/salinity-mediated-transcriptional-and-post-translational-regulation-of-the-arabidopsis-aquaporin-pip2-7
#20
Alicia Pou, Linda Jeanguenin, Thomas Milhiet, Henri Batoko, François Chaumont, Charles Hachez
Salt stress triggers a simultaneous transcriptional repression and aquaporin internalization to modify root cell water conductivity. Plasma membrane intrinsic proteins (PIPs) are involved in the adjustment of plant water balance in response to changing environmental conditions. In this study, Arabidopsis wild-type (Col-0) and transgenic lines overexpressing PIP2;7 were used to investigate and compare their response to salt stress. Hydraulic conductivity measurements using a high-pressure flowmeter (HPFM) revealed that overexpression of PIP2;7 induced a sixfold increase in root hydraulic conductivity of four week-old Arabidopsis thaliana plants compared to WT...
September 26, 2016: Plant Molecular Biology
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