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https://www.readbyqxmd.com/read/29789657/the-cooh-terminal-domain-of-huntingtin-interacts-with-rhogef-kalirin-and-modulates-cell-survival
#1
Hollis McClory, Xiaolong Wang, Ellen Sapp, Leah W Gatune, Maria Iuliano, Chiu-Yi Wu, Gina Nathwani, Kimberly B Kegel-Gleason, Marian DiFiglia, Xueyi Li
Human huntingtin (Htt) contains 3144 amino acids and has an expanded polyglutamine region near the NH2 -terminus in patients with Huntington's disease. While numerous binding partners have been identified to NH2 -terminal Htt, fewer proteins are known to interact with C-terminal domains of Htt. Here we report that kalirin, a Rac1 activator, is a binding partner to C-terminal Htt. Kalirin and Htt co-precipitated from mouse brain endosomes and co-localized at puncta in NRK and immortalized striatal cells and primary cortical neurons...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29733381/the-longevity-snp-rs2802292-uncovered-hsf1-activates-stress-dependent-expression-of-foxo3-through-an-intronic-enhancer
#2
Valentina Grossi, Giovanna Forte, Paola Sanese, Alessia Peserico, Tugsan Tezil, Martina Lepore Signorile, Candida Fasano, Rosaura Lovaglio, Rosanna Bagnulo, Daria C Loconte, Francesco C Susca, Nicoletta Resta, Cristiano Simone
The HSF and FOXO families of transcription factors play evolutionarily conserved roles in stress resistance and lifespan. In humans, the rs2802292 G-allele at FOXO3 locus has been associated with longevity in all human populations tested; moreover, its copy number correlated with reduced frequency of age-related diseases in centenarians. At the molecular level, the intronic rs2802292 G-allele correlated with increased expression of FOXO3, suggesting that FOXO3 intron 2 may represent a regulatory region. Here we show that the 90-bp sequence around the intronic single nucleotide polymorphism rs2802292 has enhancer functions, and that the rs2802292 G-allele creates a novel HSE binding site for HSF1, which induces FOXO3 expression in response to diverse stress stimuli...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29689640/haploid-genetic-screens-identify-genetic-vulnerabilities-to-microtubule-targeting-agents
#3
Nora M Gerhards, Vincent A Blomen, Merve Mutlu, Joppe Nieuwenhuis, Denise Howald, Charlotte Guyader, Jos Jonkers, Thijn R Brummelkamp, Sven Rottenberg
The absence of biomarkers to accurately predict anticancer therapy response remains a major obstacle in clinical oncology. We applied a genome-wide loss-of-function screening approach in human haploid cells to characterize genetic vulnerabilities to classical microtubule-targeting agents. Using docetaxel and vinorelbine, two well-established chemotherapeutic agents, we sought to identify genetic alterations sensitizing human HAP1 cells to these drugs. Despite the fact that both drugs act on microtubules, a set of distinct genes were identified whose disruption affects drug sensitivity...
June 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29663646/isobaric-tag-based-protein-profiling-of-a-nicotine-treated-alpha7-nicotinic-receptor-null-human-haploid-cell-line
#4
Joao A Paulo, Steven P Gygi
Nicotinic acetylcholine receptors (nAChR), the primary cell surface targets of nicotine, have implications in various neurological disorders. Here we investigate the proteome-wide effects of nicotine on human haploid cell lines (wildtype HAP1 and α7KO-HAP1) to address differences in nicotine-induced protein abundance profiles between these cell lines. We performed an SPS-MS3-based TMT10-plex experiment arranged in a 2-3-2-3 design with two replicates of the untreated samples and three of the treated samples for each cell line...
June 2018: Proteomics
https://www.readbyqxmd.com/read/29642684/monitoring-conservation-effects-on-a-chinese-indigenous-chicken-breed-using-mhc-b-g-gene-and-dna-barcodes
#5
Jianmin Zou, Yun-Jie Tu, JIngting Shu, Gaige Ji, Ming Zhang
Objective: We report monitoring conservation effect for a Chinese indigenous chicken (Langshan) breed using MHC and DNA barcords. Methods: The full length of MHC B-G gene and mitochondrial COⅠ gene in generations 0, 5 , 10, 15 , 16 and 17 was measured using re-sequencing and sequencing procedures,respectively. Results: There were 292 SNPs of MHC B-G gene identified in six generations. He and PIC of MHC B-G gene in generations 10, 15, 16, and 17 remained stable...
April 11, 2018: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29566760/vascular-biosafety-of-commercial-hydroxyapatite-particles-discrepancy-between-blood-compatibility-assays-and-endothelial-cell-behavior
#6
Catarina Santos, Suzy Turiel, Pedro Sousa Gomes, Elísio Costa, Alice Santos-Silva, Paulo Quadros, José Duarte, Sílvia Battistuzzo, Maria Helena Fernandes
BACKGROUND: Vascular homeostasis is ensured by a dynamic interplay involving the endothelium, the platelets and the coagulation system. Thus, the vascular safety of particulate materials must address this integrated system, an approach that has been largely neglected. This work analysed the effects of commercial hydroxyapatite (HA) particles in blood compatibility and in endothelial cell behavior, due to their clinical relevance and scarcity of data on their vascular biosafety. RESULTS: Particles with similar chemical composition and distinct size and morphology were tested, i...
March 22, 2018: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29542091/the-regulation-of-monoamine-oxidase-a-gene-expression-by-distinct-variable-number-tandem-repeats
#7
Maurizio Manca, Veridiana Pessoa, Ana Illera Lopez, Patrick T Harrison, Fabio Miyajima, Helen Sharp, Andrew Pickles, Jonathan Hill, Chris Murgatroyd, Vivien J Bubb, John P Quinn
The monoamine oxidase A (MAOA) uVNTR (upstream variable number tandem repeat) is one of the most often cited examples of a gene by environment interaction (GxE) in relation to behavioral traits. However, MAOA possesses a second VNTR, 500 bp upstream of the uVNTR, which is termed d- or distal VNTR. Furthermore, genomic analysis indicates that there are a minimum of two transcriptional start sites (TSSs) for MAOA, one of which encompasses the uVNTR within the 5' untranslated region of one of the isoforms. Through expression analysis in semi-haploid HAP1 cell lines genetically engineered in order to knockout (KO) either the uVNTR, dVNTR, or both VNTRs, we assessed the effect of the two MAOA VNTRs, either alone or in combination, on gene expression directed from the different TSSs...
March 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29511621/robust-dna-repair-in-paxx-deficient-mammalian-cells
#8
Alisa Dewan, Mengtan Xing, Marie Benner Lundbæk, Raquel Gago-Fuentes, Carole Beck, Per Arne Aas, Nina-Beate Liabakk, Siri Sæterstad, Khac Thanh Phong Chau, Bodil Merete Kavli, Valentyn Oksenych
To ensure genome stability, mammalian cells employ several DNA repair pathways. Nonhomologous DNA end joining (NHEJ) is the DNA repair process that fixes double-strand breaks throughout the cell cycle. NHEJ is involved in the development of B and T lymphocytes through its function in V(D)J recombination and class switch recombination (CSR). NHEJ consists of several core and accessory factors, including Ku70, Ku80, XRCC4, DNA ligase 4, DNA-PKcs, Artemis, and XLF. Paralog of XRCC4 and XLF (PAXX) is the recently described accessory NHEJ factor that structurally resembles XRCC4 and XLF and interacts with Ku70/Ku80...
March 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29487587/the-initiation-factors-eif2-eif2a-eif2d-eif4a-and-eif4g-are-not-involved-in-translation-driven-by-hepatitis-c-virus-ires-in-human-cells
#9
Esther González-Almela, Hugh Williams, Miguel A Sanz, Luis Carrasco
Animal viruses have evolved a variety of strategies to ensure the efficient translation of their mRNAs. One such strategy is the use of internal ribosome entry site (IRES) elements, which circumvent the requirement for some eukaryotic initiation factors (eIFs). Much effort has been directed to unravel the precise mechanism of translation initiation by hepatitis C virus (HCV) mRNA. In the present study, we examined the involvement of several eIFs in HCV IRES-driven translation in human cells in a comparative analysis with mRNAs bearing the encephalomyocarditis virus or the Cricket paralysis virus IRES element...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29474001/proteogenomic-analysis-to-identify-missing-proteins-from-haploid-cell-lines
#10
Seung-Eun Lee, JongKeon Song, Korbinian Bösl, André C Müller, Dijana Vitko, Keiryn L Bennett, Giulio Superti-Furga, Akhilesh Pandey, Richard K Kandasamy, Min-Sik Kim
Chromosome-centric Human Proteome Project aims at identifying and characterizing protein products encoded from all human protein-coding genes. As of early 2017, 19 837 protein-coding genes have been annotated in the neXtProt database including 2691 missing proteins that have never been identified by mass spectrometry. Missing proteins may be low abundant in many cell types or expressed only in a few cell types in human body such as sperms in testis. In this study, we performed expression proteomics of two near-haploid cell types such as HAP1 and KBM-7 to hunt for missing proteins...
April 2018: Proteomics
https://www.readbyqxmd.com/read/29463790/contribution-of-tmem16f-to-pyroptotic-cell-death
#11
Jiraporn Ousingsawat, Podchanart Wanitchakool, Rainer Schreiber, Karl Kunzelmann
Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+ activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X7 receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca2+ , we asked whether TMEM16F is activated during pyroptosis...
February 20, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447841/crispr-cas9-generated-human-cd46-cd55-and-cd59-knockout-cell-lines-as-a-tool-for-complement-research
#12
Astrid J F Thielen, Iris M van Baarsen, Marlieke L Jongsma, Sacha Zeerleder, Robbert M Spaapen, Diana Wouters
BACKGROUND: To prevent unwanted complement activation and subsequent damage, complement activation must be tightly regulated on healthy host cells. Dysregulation of the complement system contributes to the pathology of diseases like Paroxysmal Nocturnal Hemoglobinuria and atypical Hemolytic Uremic Syndrome. To investigate complement regulator deficiencies, primary patient cells may be used, but access to patient cells may be limited and cells are heterogeneous between different patients...
May 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29425499/bub1-is-essential-for-the-viability-of-human-cells-in-which-the-spindle-assembly-checkpoint-is-compromised
#13
Jonne A Raaijmakers, Roy G H P van Heesbeen, Vincent A Blomen, Louise M E Janssen, Ferdy van Diemen, Thijn R Brummelkamp, René H Medema
The spindle assembly checkpoint (SAC) ensures faithful segregation of chromosomes. Although most mammalian cell types depend on the SAC for viability, we found that human HAP1 cells can grow SAC independently. We generated MAD1- and MAD2-deficient cells and mutagenized them to identify synthetic lethal interactions, revealing that chromosome congression factors become essential upon SAC deficiency. Besides expected hits, we also found that BUB1 becomes essential in SAC-deficient cells. We found that the BUB1 C terminus regulates alignment as well as recruitment of CENPF...
February 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29324738/population-structure-analysis-of-the-neglected-parasite-thelazia-callipaeda-revealed-high-genetic-diversity-in-eastern-asia-isolates
#14
Xi Zhang, Ya Li Shi, Lu Lu Han, Chen Xiong, Shi Qi Yi, Peng Jiang, Zeng Xian Wang, Ji Long Shen, Jing Cui, Zhong Quan Wang
BACKGROUND: Thelazia callipaeda is the causative agent of thelaziasis in canids, felids and humans. However, the population genetic structure regarding this parasite remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we first explored the genetic variation of 32 T. callipaeda clinical isolates using the following multi-molecular markers: cox1, cytb, 12S rDNA, ITS1 and 18S rDNA. The isolates were collected from 13 patients from 11 geographical locations in China...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29258561/a-pilot-investigation-on-dna-methylation-modifications-associated-with-complex-posttraumatic-symptoms-in-elderly-traumatized-in-childhood
#15
Zoya Marinova, Andreas Maercker, Edna Grünblatt, Tomasz K Wojdacz, Susanne Walitza
OBJECTIVE: Complex posttraumatic stress disorder (CPTSD) is a newly proposed diagnosis in the International Classification of Diseases-version 11, which is currently intensively investigated. Childhood trauma is regarded as main source of CPTSD symptoms, even in later life. Induction of DNA methylation changes by childhood trauma may contribute to its long-lasting adverse health consequences. The current study analyzed the correlation of genome-wide DNA methylation profiles with complex posttraumatic sequelae in buccal epithelial cells from 31 elderly former indentured child laborers (Verdingkinder) using the Infinium Illumina 450k Human DNA methylation chip...
December 19, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28922634/functionalisation-of-ti6al4v-and-hydroxyapatite-surfaces-with-combined-peptides-based-on-kklpda-and-eeeeeeee-peptides
#16
Gabriela Melo Rodriguez, James Bowen, David Grossin, Besim Ben-Nissan, Artemis Stamboulis
Surface modifications are usually performed on titanium alloys to improve osteo-integration and surface bioactivity. Modifications such as alkaline and acid etching, or coating with bioactive materials such as hydroxyapatite, have previously been demonstrated. The aim of this work is to develop a peptide with combined titanium oxide and hydroxyapatite binders in order to achieve a biomimetic hydroxyapatite coating on titanium surfaces. The technology would also be applicable for the functionalisation of titanium and hydroxyapatite surfaces for selective protein adsorption, conjugation of antimicrobial peptides, and adsorption of specialised drugs for drug delivery...
December 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28885064/araniella-cucurbitina-the-first-molecular-evidence-of-a-palearctic-species-of-genus-araniella-inhabiting-india
#17
Ankita Rajpoot, Ved Prakash Kumar, Archana Bahuguna, Pallab Maity, Dhyanendra Kumar
The present study represents first genetic record of single spider species Araniella cucurbitina, genus Araniella from Uttarakhand, India. There are 12 identified species under Araniella genus and they are distributed in Palearctic region. Here, we used known N = 47 (2 from present study and 45 from GenBank) cytochrome oxidase 1 (CO1) sequences of A. cucurbitina representing seven different geographical groups, additionally 23 sequences of eight Araniella species were used for phylogenetic relationship...
September 8, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28842783/population-genetics-of-ifitm3-in-portugal-and-central-africa-reveals-a-potential-modifier-of-influenza-severity
#18
Susana David, Vanessa Correia, Liliana Antunes, Ricardo Faria, José Ferrão, Paula Faustino, Baltazar Nunes, Fernando Maltez, João Lavinha, Helena Rebelo de Andrade
Influenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified...
March 2018: Immunogenetics
https://www.readbyqxmd.com/read/28808015/a-p53-dependent-response-limits-the-viability-of-mammalian-haploid-cells
#19
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 29, 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
#20
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...
September 2017: Fish & Shellfish Immunology
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