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https://www.readbyqxmd.com/read/28808015/a-p53-dependent-response-limits-the-viability-of-mammalian-haploid-cells
#1
Teresa Olbrich, Cristina Mayor-Ruiz, Maria Vega-Sendino, Carmen Gomez, Sagrario Ortega, Sergio Ruiz, Oscar Fernandez-Capetillo
The recent development of haploid cell lines has facilitated forward genetic screenings in mammalian cells. These lines include near-haploid human cell lines isolated from a patient with chronic myelogenous leukemia (KBM7 and HAP1), as well as haploid embryonic stem cells derived from several organisms. In all cases, haploidy was shown to be an unstable state, so that cultures of mammalian haploid cells rapidly become enriched in diploids. Here we show that the observed diploidization is due to a proliferative disadvantage of haploid cells compared with diploid cells...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28734968/identification-of-an-mitf-gene-and-its-polymorphisms-associated-with-the-vibrio-resistance-trait-in-the-clam-meretrix-petechialis
#2
Shujing Zhang, Xin Yue, Fengjuan Jiang, Hongxia Wang, Baozhong Liu
Microphthalmia-associated transcription factor (MITF) regulates the transcription of its target genes by binding to their promoters. In this study, an MITF gene, MpMITF was identified in the clam Meretrix petechialis. The full-length cDNA of MpMITF is 3564 bp with an ORF of 1365 bp. The deduced amino acid sequence consists of a conserved functional structure of bHLH-LZ, which could bind with E-box. The mRNA and protein expression levels of MpMITF were significantly up-regulated 6 h post-Vibrio injection. The mRNA expression of MpMITF increased on day 2 and peaked on day 10 post-Vibrio immersion...
July 19, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28691208/transcriptomic-profile-analysis-of-mouse-neural-tube-development-by-rna-seq
#3
Juan Yu, Jianbing Mu, Qian Guo, Lihong Yang, Juan Zhang, Zhizhen Liu, Baofeng Yu, Ting Zhang, Jun Xie
The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA-seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles...
July 10, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28679759/mutational-analysis-of-lassa-virus-glycoprotein-highlights-regions-required-for-alpha-dystroglycan-utilization
#4
Marissa Acciani, Jacob T Alston, Guohui Zhao, Hayley Reynolds, Afroze M Ali, Brian Xu, Melinda A Brindley
Lassa virus (LASV) is an enveloped RNA virus endemic to West Africa and responsible for severe cases of hemorrhagic fever. Virus entry is mediated by the glycoprotein complex consisting of a stable signal peptide, a receptor-binding subunit GP1, and a viral-host membrane fusion subunit GP2. Several cellular receptors can interact with the GP1 subunit and mediate viral entry, including alpha-dystroglycan (αDG) and lysosomal associated membrane protein 1 (LAMP1). In order to define the regions within GP1 that interact with the cellular receptors, we implemented insertional mutagenesis, carbohydrate shielding, and alanine scanning mutagenesis...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28606035/potential-minor-haplotypes-of-cyp2d6-in-the-japanese-population
#5
Masatoshi Masuda, Tsutomu Fujiwara, Masayuki Matsunaga, Takehisa Matsumaru
BACKGROUND: CYP2D6 is one of the most significant polymorphic genes of drug-metabolizing enzymes due to its association with different metabolic activities and the pharmacokinetics of CYP2D6 substrates. OBJECTIVE: The objective of this study was to explore for a novel haplotype of CYP2D6 in the Japanese population by using a large database of previous clinical studies. METHODS: We analyzed CYP2D6 genotype data from a total of 723 Japanese individuals for 8 loci (100C>T, 1758G>A, 1846G>A, 2573 insertion of C, 2850C>T, 2988G>A, 4125 insertion of 9bp, and 4180G>C) and gene deletion...
June 12, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28503666/robust-long-read-native-dna-sequencing-using-the-ont-csgg-nanopore-system
#6
Jean-Michel Carter, Shobbir Hussain
Background: The ability to obtain long read lengths during DNA sequencing has several potentially important practical applications. Especially long read lengths have been reported using the Nanopore sequencing method, currently commercially available from Oxford Nanopore Technologies (ONT). However, early reports have demonstrated only limited levels of combined throughput and sequence accuracy. Recently, ONT released a new CsgG pore sequencing system as well as a 250b/s translocation chemistry with potential for improvements...
April 6, 2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28404855/genome-wide-screening-uncovers-the-significance-of-n-sulfation-of-heparan-sulfate-as-a-host-cell-factor-for-chikungunya-virus-infection
#7
Atsushi Tanaka, Uranan Tumkosit, Shota Nakamura, Daisuke Motooka, Natsuko Kishishita, Thongkoon Priengprom, Areerat Sa-Ngasang, Taroh Kinoshita, Naokazu Takeda, Yusuke Maeda
The molecular mechanisms underlying chikungunya virus (CHIKV) infection are poorly characterized. In this study, we analyzed the host factors involved in CHIKV infection using genome-wide screening. Human haploid HAP1 cells, into which an exon-trapping vector was introduced, were challenged with a vesicular stomatitis virus pseudotype bearing the CHIKV E3 to E1 envelope proteins. Analysis of genes enriched in the cells resistant to the pseudotyped virus infection unveiled a critical role of N-sulfation of heparan sulfate (HS) for the infectivity of the clinically isolated CHIKV Thai#16856 strain to HAP1 cells...
July 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28389297/fbxo25-regulates-mapk-signaling-pathway-through-inhibition-of-erk1-2-phosphorylation
#8
Felipe R Teixeira, Adriana O Manfiolli, Nichelle A Vieira, Ana Carla Medeiros, Priscila de O Coelho, Dimitrius Santiago Guimarães, Deborah Schechtman, Marcelo D Gomes
The FBXO25 mediates degradation of ELK-1 and thus inhibits transcriptional activation of immediate early genes (iEG). Here we show that FBXO25 regulates yet another node of this signaling pathway, by decreasing MAPK/ERK activity. We show that induction of FBXO25 reduced ERK1/2 phosphorylation independently of MEK1/2. Accordingly, in HAP1 FBXO25 knockout cells (FBXO25(KO)), we observed that upon PMA treatment ERK1/2 was more active than in parental cells. An increase in cell proliferation under receptor mediated activation of the ERK signaling pathway in FBXO25(KO) cells was also observed...
May 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28289229/persistence-of-the-mitochondrial-permeability-transition-in-the-absence-of-subunit-c-of-human-atp-synthase
#9
Jiuya He, Holly C Ford, Joe Carroll, Shujing Ding, Ian M Fearnley, John E Walker
The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane, and ATP synthesis, followed by cell death. Recent proposals suggest that the pore is associated with the ATP synthase complex and specifically with the ring of c-subunits that constitute the membrane domain of the enzyme's rotor...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28267410/combined-haplotypes-of-casr-gene-sequence-variants-and-their-associations-with-growth-traits-in-cattle
#10
Binglin Yue, Fuhai Han, Jiyao Wu, Yanhuan Wang, Chunlei Zhang, Xingtang Fang, Xinglei Qi, Yueyu Bai, Hong Chen
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor that regulates food intake and assimilation. However, studies on the relationship between CaSR gene and growth traits in cattle are deficient. The aim of this study was to examine the association of the CaSR polymorphism with growth traits in cattle breeds. Four novel single nucleotide polymorphisms (SNPs) and one previously reported SNP (NC_007299.5: g.67630865T>C, 67638409G>C, 67660395G>C, 67661546C>G, and 67661892A>C) were identified in the bovine CaSR gene using DNA sequencing and PCR-SSCP methods in 520 individuals from three representative breeds...
March 7, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28259758/huntingtin-associated-protein-1-hap1-regulates-endocytosis-and-interacts-with-multiple-trafficking-related-proteins
#11
Kimberly D Mackenzie, Yoon Lim, Michael D Duffield, Timothy Chataway, Xin-Fu Zhou, Damien J Keating
Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1...
March 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28240315/translation-of-sindbis-subgenomic-mrna-is-independent-of-eif2-eif2a-and-eif2d
#12
Miguel Angel Sanz, Esther González Almela, Luis Carrasco
Translation of Sindbis virus subgenomic mRNA (sgmRNA) can occur after inactivation of eIF2 by phosphorylation in mammalian cells. Several studies have suggested that eIF2 can be replaced by eIF2A or eIF2D. HAP1 human cell lines knocked-out for eIF2A, eIF2D or both by CRISPR/Cas9 genome engineering were compared with wild-type (WT) cells to test the potential role of eIF2A and eIF2D in translation. Sindbis virus infection was comparable between the four cell lines. Moreover, synthesis of viral proteins during late stage infection was similar in all four cell lines despite the fact that eIF2α became phosphorylated...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228588/investigation-of-the-role-of-protein-kinase-d-in-human-rhinovirus-replication
#13
Anabel Guedán, Dawid Swieboda, Mark Charles, Marie Toussaint, Sebastian L Johnston, Amin Asfor, Anusha Panjwani, Tobias J Tuthill, Henry Danahay, Tony Raynham, Aurelie Mousnier, Roberto Solari
Picornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi membrane vesicular and lipid transport, we hypothesized that PKD played a role in viral replication...
May 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28137862/dyrk1a-regulates-hap1-dcaf7-wdr68-binding-with-implication-for-delayed-growth-in-down-syndrome
#14
Jianxing Xiang, Su Yang, Ning Xin, Marta A Gaertig, Roger H Reeves, Shihua Li, Xiao-Jiang Li
Huntingtin-associated protein 1 (Hap1) is known to be critical for postnatal hypothalamic function and growth. Hap1 forms stigmoid bodies (SBs), unique neuronal cytoplasmic inclusions of unknown function that are enriched in hypothalamic neurons. Here we developed a simple strategy to isolate the SB-enriched fraction from mouse brain. By analyzing Hap1 immunoprecipitants from this fraction, we identified a Hap1-interacting SB component, DDB1 and CUL4 associated factor 7 (Dcaf7)/WD40 repeat 68 (WDR68), whose protein level and nuclear translocation are regulated by Hap1...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28003220/recycling-of-apolipoprotein-a-after-plgrkt-mediated-endocytosis-of-lipoprotein-a
#15
Monika Sharma, Gregory M Redpath, Michael J A Williams, Sally P A McCormick
RATIONALE: Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like lipoprotein and important cardiovascular risk factor whose cognate receptor and intracellular fate remains unknown. OBJECTIVE: Our study aimed to determine the intracellular trafficking pathway for Lp(a) and the receptor responsible for its uptake in liver cells. METHODS AND RESULTS: Human hepatoma cells were treated with Lp(a) purified from human plasma and Lp(a) uptake studied using Western blot analysis and intracellular localization of Lp(a) by confocal microscopy...
March 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/27984179/immunohistochemical-analysis-of-huntingtin-associated-protein-1-in-adult-rat-spinal-cord-and-its-regional-relationship-with-androgen-receptor
#16
Md Nabiul Islam, Yukio Takeshita, Akie Yanai, Amami Imagawa, Mir Rubayet Jahan, Greggory Wroblewski, Joe Nemoto, Ryutaro Fujinaga, Koh Shinoda
Huntingtin-associated protein 1 (HAP1) is a neuronal interactor with causatively polyglutamine (polyQ)-expanded huntingtin in Huntington's disease and also associated with pathologically polyQ-expanded androgen receptor (AR) in spinobulbar muscular atrophy (SBMA), being considered as a protective factor against neurodegenerative apoptosis. In normal brains, it is abundantly expressed particularly in the limbic-hypothalamic regions that tend to be spared from neurodegeneration, whereas the areas with little HAP1 expression, including the striatum, thalamus, cerebral neocortex and cerebellum, are targets in several neurodegenerative diseases...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27979739/genetic-variants-in-sirt3-transcriptional-regulatory-region-affect-promoter-activity-and-fat-deposition-in-three-cattle-breeds
#17
Linsheng Gui, Jieyun Hong, Sayed Haidar Abbas Raza, Linsen Zan
Sirtuin 3 (SIRT3) is a mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase. It has crucial roles in regulating the respiratory chain, in adenosine triphosphate (ATP) production, and in both the citric acid and urea cycles. The aim of this study was to investigate whether SIRT3 could be used as a candidate gene in the breeding of cattle. Expression analysis by quantitative real-time polymerase chain reactions (qPCR) indicated that expression levels of SIRT3 were highest in the kidney, rumen, liver, omasum and muscle...
December 12, 2016: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/27737633/huntingtin-associated-protein-1-eutherian-adaptation-from-a%C3%A2-trak-like-protein-conserved-gene-promoter-elements-and-localization-in-the-human-intestine
#18
Amanda L Lumsden, Richard L Young, Nektaria Pezos, Damien J Keating
BACKGROUND: Huntingtin-associated Protein 1 (HAP1) is expressed in neurons and endocrine cells, and is critical for postnatal survival in mice. HAP1 shares a conserved "HAP1_N" domain with TRAfficking Kinesin proteins TRAK1 and TRAK2 (vertebrate), Milton (Drosophila) and T27A3.1 (C. elegans). HAP1, TRAK1 and TRAK2 have a degree of common function, particularly regarding intracellular receptor trafficking. However, TRAK1, TRAK2 and Milton (which have a "Milt/TRAK" domain that is absent in human and rodent HAP1) differ in function to HAP1 in that they are mitochondrial transport proteins, while HAP1 has emerging roles in starvation response...
October 13, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27624941/regulation-of-l-type-ca2-channel-activity-and-insulin-secretion-by-huntingtin-associated-protein-1
#19
Jing-Ying Pan, Shijin Yuan, Tao Yu, Cong-Lin Su, Xiao-Long Liu, Jun He, He Li
Huntingtin-associated protein 1 (Hap1) was originally identified as a protein that binds to the Huntington disease protein, huntingtin. Growing evidence has shown that Hap1 participates in intracellular trafficking via its association with various microtubule-dependent transporters and organelles. Recent studies also revealed that Hap1 is involved in exocytosis such as insulin release from pancreatic β-cells. However, the mechanism underlying the action of Hap1 on insulin release remains to be investigated...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27519690/systematic-identification-of-genes-involved-in-metabolic-acid-stress-resistance-in-yeast-and-their-potential-as-cancer-targets
#20
John J Shin, Qurratulain Aftab, Pamela Austin, Jennifer A McQueen, Tak Poon, Shu Chen Li, Barry P Young, Calvin D Roskelley, Christopher J R Loewen
A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress...
September 1, 2016: Disease Models & Mechanisms
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