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https://www.readbyqxmd.com/read/28813671/oct4-and-sox2-work-as-transcriptional-activators-in-reprogramming-human-fibroblasts
#1
Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28810153/evaluation-of-affibody-molecule-based-pna-mediated-radionuclide-pretargeting-development-of-an-optimized-conjugation-protocol-and-177-lu-labeling
#2
Mohamed Altai, Kristina Westerlund, Justin Velletta, Bogdan Mitran, Hadis Honarvar, Amelie Eriksson Karlström
INTRODUCTION: We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA-PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide (177)Lu. We also studied the biodistribution profile of (177)Lu-HP2 in mice, and evaluated pretargeting with (177)Lu-HP2 in vitro and in vivo. METHODS: The biodistribution profile of (177)Lu-HP2 was evaluated in NMRI mice and compared to the previously studied (111)In-HP2...
July 12, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28782354/a-novel-ternary-electrochemiluminescence-system-based-on-rubrene-microrods-as-luminophore-and-pt-nanomaterials-as-coreaction-accelerator-for-ultrasensitive-detection-of-microrna-from-cancer-cells
#3
Jia-Li Liu, Zhi-Ling Tang, Ying Zhuo, Yaqin Chai, Ruo Yuan
As the only endogenous co-reactant in ECL system, the dissolved O2 was the ideal candidate due to the mild reaction and easy operation, but compared to S2O82-, the dissolved O2 with weaker redox activity suffers from the poor enhancement effect of luminophore, which restricted the further application in bioanalysis. Here, a high-intense ECL signal was gained by the employing of Pt nanomaterials as co-reaction accelerator to generate more intermediate of dissolved O2 to promote the co-reaction efficiency. Based on a new ternary ECL system of Pt nanomaterials as the co-reaction accelerator, dissolved O2 as co-reactant, and a neotype rubrene microrods as luminophore, an efficient "on-off-on" solid-state ECL switch platfrom was designed for ultrasensitive microRNA (miRNA) detection with a background reduction strategy of ferrocene-labeled single-stranded DNA (Fc-DNA) as a quencher...
August 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28698785/haptoglobin-phenotypes-and-susceptibility-to-schistosoma-parasites-infection-in-central-sudan
#4
Ashraf Siddig Yousif, Atif Abdelrahman Elagib
Haptoglobin (Hp) is an acute phase protein that binds the free hemoglobin (Hb), thus preventing iron loss and renal damage. Hp also has antioxidative and immunomodulatory properties. Three Hp phenotypes have been identified in human: Hp1-1, Hp2-1, and Hp2-2. Hp polymorphisms have been related to susceptibility of various diseases. In this study, we aimed to assess the possible association of Hp phenotypes polymorphism to Schistosoma parasites infection in central Sudan. We have investigated the Hp phenotypes polymorphism distribution in the serum of 125 (93 S...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28692189/diversification-of-hp1-like-chromo-domain-proteins-in-tetrahymena-thermophila
#5
Emily A Wiley, Scott Horrell, Alyssa Yoshino, Cara C Schornak, Claire Bagnani, Douglas L Chalker
Proteins that possess a chromo domain are well-known for their roles in heterochromatin assembly and maintenance. The Heterochromatin Protein 1 (HP1) family, with a chromo domain and carboxy-terminal chromo shadow domain, targets heterochromatin through interaction with histone H3 methylated on lysine 9 (H3K9me2/3). The structural and functional diversity of these proteins observed in both fission yeast and metazoans correlate with chromatin specialization. To expand these studies, we examined chromo domain proteins in the ciliate Tetrahymena thermophila, which has functionally diverse and developmentally regulated heterochromatin domains...
July 10, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28684548/lem-domain-proteins-are-lost-during-human-spermiogenesis-but-baf-and-baf-l-persist
#6
Razan A Elkhatib, Marine Paci, Romain Boissier, Guy Longepied, Yasmina Auguste, Vincent Achard, Patrice Bourgeois, Nicolas Levy, Nicolas Branger, Michael J Mitchell, Catherine Metzler-Guillemain
During spermiogenesis the spermatid nucleus is elongated, and dramatically reduced in size with protamines replacing histones to produce a highly compacted chromatin. After fertilisation, this process is reversed in the oocyte to form the male pronucleus. Emerging evidence, including the coordinated loss of the nuclear lamina (NL) and the histones, supports the involvement of the NL in spermatid nuclear remodelling, but how the NL links to the chromatin is not known. In somatic cells, interactions between the NL and the chromatin have been demonstrated: LEM-domain proteins and LBR interact with the NL and, respectively, the chromatin proteins BAF and HP1...
July 6, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28659611/a-common-deletion-in-the-haptoglobin-gene-associated-with-blood-cholesterol-levels-among-chinese-women
#7
Neil S Zheng, Lisa A Bastarache, Julie A Bastarache, Yingchang Lu, Lorraine B Ware, Xiao-Ou Shu, Joshua C Denny, Jirong Long
Haptoglobin (HP) protein plays a critical role in binding and removing free hemoglobin from blood. A deletion in the HP gene affects the protein structure and function. A recent study developed a novel method to impute this variant and discovered significant association of this variant with low-density lipoprotein (LDL) and total cholesterol levels among European descendants. In the present study, we investigated this variant among 3608 Chinese women. Consistent with findings from Europeans, we found significant associations between the deletion with lower cholesterol levels; women homozygous for the deletion allele (HP1-HP1), had a lower level of total cholesterol (-4...
June 29, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28636604/liquid-droplet-formation-by-hp1%C3%AE-suggests-a-role-for-phase-separation-in-heterochromatin
#8
Adam G Larson, Daniel Elnatan, Madeline M Keenen, Michael J Trnka, Jonathan B Johnston, Alma L Burlingame, David A Agard, Sy Redding, Geeta J Narlikar
Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands...
July 13, 2017: Nature
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#9
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
July 13, 2017: Nature
https://www.readbyqxmd.com/read/28622804/g-quadruplex-based-exo-iii-assisted-signal-amplification-aptasensor-for-the-colorimetric-detection-of-adenosine
#10
Lei Xu, Xin Shen, Bingzhi Li, Chunhong Zhu, Xuemin Zhou
Adenosine is an endogenous nucleotide pivotally involved in nucleic acid and energy metabolism. Its excessive existence may indicate tumorigenesis, typically lung cancer. Encouraged by its significance as the clinical biomarker, sensitive assay methods towards adenosine have been popularized, with high cost and tedious procedures as the inevitable defects. Herein, we report a label-free aptamer-based exonuclease III (Exo III) amplification colorimetric aptasensor for the highly sensitive and cost-effective detection of adenosine...
August 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#11
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#12
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525753/the-u6-snrna-m-6-a-methyltransferase-mettl16-regulates-sam-synthetase-intron-retention
#13
Kathryn E Pendleton, Beibei Chen, Kuanqing Liu, Olga V Hunter, Yang Xie, Benjamin P Tu, Nicholas K Conrad
Maintenance of proper levels of the methyl donor S-adenosylmethionine (SAM) is critical for a wide variety of biological processes. We demonstrate that the N(6)-adenosine methyltransferase METTL16 regulates expression of human MAT2A, which encodes the SAM synthetase expressed in most cells. Upon SAM depletion by methionine starvation, cells induce MAT2A expression by enhanced splicing of a retained intron. Induction requires METTL16 and its methylation substrate, a vertebrate conserved hairpin (hp1) in the MAT2A 3' UTR...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28514126/-haptoglobin-polymorphism-as-an-independent-predictor-of-diabetic-nephropathy-and-retinopathy
#14
Inbal Dahan, Nadia Thauho, Farid Nakhoul, Nakhoul Nakhoul, Hanin Jabaly, Evgeny Farber
The antioxidant protein haptoglobin (Hp) plays a major role in the development of diabetic complications such as diabetic nephropathy and retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their biochemical and biophysical properties, such as their antioxidant capacity. The Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and neutralizing its oxidative potential and the accompanying renal and retinal injury...
July 2016: Harefuah
https://www.readbyqxmd.com/read/28487337/haptoglobin-hp2-variant-promotes-premature-cardiovascular-death-in-stroke-survivors
#15
Petra Ijäs, Susanna Melkas, Jani Saksi, Antti Jula, Matti Jauhiainen, Niku Oksala, Tarja Pohjasvaara, Markku Kaste, Pekka J Karhunen, Perttu Lindsberg, Timo Erkinjuntti
BACKGROUND AND PURPOSE: Haptoglobin (Hp) is an acute phase plasma protein protecting tissues from oxidative damage. It exists in 2 variant alleles (hp1/hp2) giving rise to 3 protein isoforms with different biochemical properties and efficiency to limit oxidative stress. We previously found that hp2 variant is associated with stroke risk in the patients with carotid stenosis and the risk of ischemic cardiovascular events in a general population cohort. This study examined the hypothesis that Hp genotype is associated with general cardiovascular risk in patients with stroke...
June 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28483815/drosophila-dalmatian-combines-sororin-and-shugoshin-roles-in-establishment-and-protection-of-cohesion
#16
Takashi Yamada, Eri Tahara, Mai Kanke, Keiko Kuwata, Tomoko Nishiyama
Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Drosophila Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin...
June 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28459455/dna-sequence-homology-induces-cytosine-to-thymine-mutation-by-a-heterochromatin-related-pathway-in-neurospora
#17
Eugene Gladyshev, Nancy Kleckner
Most eukaryotic genomes contain substantial amounts of repetitive DNA organized in the form of constitutive heterochromatin and associated with repressive epigenetic modifications, such as H3K9me3 and C5 cytosine methylation (5mC). In the fungus Neurospora crassa, H3K9me3 and 5mC are catalyzed, respectively, by a conserved SUV39 histone methyltransferase, DIM-5, and a DNMT1-like cytosine methyltransferase, DIM-2. Here we show that DIM-2 can also mediate repeat-induced point mutation (RIP) of repetitive DNA in N...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28416369/plasma-levels-of-apolipoprotein-a1-and-lecithin-cholesterol-acyltransferase-in-type-2-diabetes-mellitus-correlations-with-haptoglobin-phenotypes
#18
Samir Awadallah, Mohammed Madkour, Reem Al Hamidi, Esraa Abo Alwafa, Maram Hattab, Buhour Zakkour, Amna Al-Matroushi, Eslah Ahmed, Mariam Al-Kitbi
BACKGROUND: Previous studies have demonstrated that hemoglobin-haptoglobin (Hb-Hp) complex plays a role in developing vascular complications in type 2 diabetes mellitus (T2DM). The complexes bind with Apolipoprotein A1 (ApoA1) of high-density lipoprotein (HDL), affecting the function of Lecithin:Cholesterol Acyltransferase (LCAT), and impairing the reverse cholesterol transport mechanism (RCT). This study investigated the influence of Hp phenotypes on serum levels of ApoA1 and LCAT in patients with T2DM...
April 7, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28398513/a-rare-splice-donor-mutation-in-the-haptoglobin-gene-associates-with-blood-lipid-levels-and-coronary-artery-disease
#19
Eythor Bjornsson, Hannes Helgason, Gisli Halldorsson, Anna Helgadottir, Arnaldur Gylfason, Birte Kehr, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Asmundur Oddsson, Gudmar Thorleifsson, Olafur Th Magnusson, Solveig Gretarsdottir, Florian Zink, Ragnar P Kristjansson, Margret Asgeirsdottir, Dorine W Swinkels, Lambertus A Kiemeney, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Gisli Masson, Isleifur Olafsson, Gudmundur Thorgeirsson, Hilma Holm, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Patrick Sulem, Kari Stefansson
Common sequence variants at the haptoglobin gene (HP) have been associated with blood lipid levels. Through whole-genome sequencing of 8,453 Icelanders, we discovered a splice donor founder mutation in HP (NM_001126102.1:c.190 + 1G > C, minor allele frequency = 0.56%). This mutation occurs on the HP1 allele of the common copy number variant in HP and leads to a loss of function of HP1. It associates with lower levels of haptoglobin (P = 2.1 × 10-54), higher levels of non-high density lipoprotein cholesterol (β = 0...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#20
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 24, 2017: Current Biology: CB
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