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https://www.readbyqxmd.com/read/28333290/evolution-of-the-genome-3d-organization-comparison-of-fused-and-segregated-globin-gene-clusters
#1
Anastasia P Kovina, Natalia V Petrova, Ekaterina S Gushchanskaya, Konstantin V Dolgushin, Evgeny S Gerasimov, Aleksandra A Galitsyna, Alexey A Penin, Ilya M Flyamer, Elena S Ioudinkova, Alexey A Gavrilov, Yegor S Vassetzky, Sergey V Ulianov, Olga V Iarovaia, Sergey V Razin
The genomes are folded in a complex three-dimensional (3D) structure. Some features of this organization are common for all eukaryotes, but little is known about its evolution. Here we have studied the 3D organization and regulation of zebrafish globin domain and compared its organization and regulation with those of other vertebrate species. In birds and mammals, the alpha- and beta-globin genes are segregated into separate clusters located on different chromosomes and organized into chromatin domains of different types, whereas in cold-blooded vertebrates, including Danio rerio, alpha- and beta-globin genes are organized into common clusters...
March 7, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28325300/one-step-biallelic-and-scarless-correction-of-a-%C3%AE-thalassemia-mutation-in-patient-specific-ipscs-without-drug-selection
#2
Yali Liu, Yi Yang, Xiangjin Kang, Bin Lin, Qian Yu, Bing Song, Ge Gao, Yaoyong Chen, Xiaofang Sun, Xiaoping Li, Lei Bu, Yong Fan
Monogenic disorders (MGDs), which are caused by single gene mutations, have a serious effect on human health. Among these, β-thalassemia (β-thal) represents one of the most common hereditary hematological diseases caused by mutations in the human hemoglobin β (HBB) gene. The technologies of induced pluripotent stem cells (iPSCs) and genetic correction provide insights into the treatments for MGDs, including β-thal. However, traditional approaches for correcting mutations have a low efficiency and leave a residual footprint, which leads to some safety concerns in clinical applications...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28304094/effects-of-blood-plasma-proteins-addition-on-physico-chemical-properties-of-emulsion-type-pork-sausage-during-cold-storage
#3
Sung Ho Kim, Sang Keun Jin, Jung Seok Choi
BACKGROUND: Most of the slaughter blood is discarded, resulting in problems related to costs for wastewater disposal and environmental pollution. However, animal blood contains various proteins such as albumin, globulin and globin and can be used as a natural emulsifier, stabilizer and color additives. Thus, this study was carried out to investigate the effect of blood plasma proteins on the physico-chemical properties of emulsion-type pork sausages stored at 4 °C over 5 weeks. RESULTS: The emulsion-type pork sausages with plasma powders had higher pH than the other treatments during weeks 5, and higher shear force than the control (p < 0...
March 17, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28303830/multiplex-polymerase-chain-reaction-for-the-detection-of-high-risk-human-papillomavirus-types-in-formalin-fixed-paraffin-embedded-cervical-tissues
#4
Mini P Singh, Nalini Gupta, T Deepak, Archit Kumar, Radha Kanta Ratho
Detecting high-risk-human papillomavirus (HPV) types has become an integral part of the cervical cancer screening programmes. This study aimed to develop a multiplex polymerase chain reaction (PCR) for identification of HPV types 16 and 18 along with the beta globin gene in formalin-fixed and paraffin-embedded cervical biopsy specimens. A total of 59 samples from patients with cervical abnormalities were tested. HPV 16 positivity was 50% in cervical cancers and 52.9% in cervical intraepithelial neoplasia. Our multiplex PCR protocol can be used as a simple and cost-effective tool for high-risk-HPV detection in cervical cancer screening programmes...
January 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28303002/reciprocal-regulation-of-%C3%AE-globin-expression-by-exo-mirnas-relevance-to-%C3%AE-globin-silencing-in-%C3%AE-thalassemia-major
#5
Kuo-Ting Sun, Yu-Nan Huang, Kalaiselvi Palanisamy, Shih-Sheng Chang, I-Kuan Wang, Kang-Hsi Wu, Ping Chen, Ching-Tien Peng, Chi-Yuan Li
Induction of fetal hemoglobin (HbF) is a promising strategy in the treatment of β-thalassemia major (β-TM). The present study shows that plasma exosomal miRNAs (exo-miRs) are involved in γ-globin regulation. Exosomes shuttle miRNAs and mediate cell-cell communication. MiRNAs are regulators of biological processes through post-transcriptional targeting. Compared to HD (Healthy Donor), β-TM patients showed increased levels of plasma exosomes and the majority of exosomes had cellular origin from CD34+ cells...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293406/%C3%AE-thalassemia-distribution-in-the-old-world-an-ancient-disease-seen-from-a-historical-standpoint
#6
REVIEW
Vincenzo De Sanctis, Christos Kattamis, Duran Canatan, Ashraf T Soliman, Heba Elsedfy, Mehran Karimi, Shahina Daar, Yasser Wali, Mohamed Yassin, Nada Soliman, Praveen Sobti, Soad Al Jaouni, Mohamed El Kholy, Bernadette Fiscina, Michael Angastiniotis
BACKGROUND: Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. β-thalassaemia is characterised by the reduced synthesis (β(+)) or absence (β(o)) of the β-globin chains in the HbA molecule, resulting in accumulation of excess unbound α-globin chains that precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral haemolysis...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28286694/highly-stereoselective-biocatalytic-synthesis-of-key-cyclopropane-intermediate-to-ticagrelor
#7
Kari E Hernandez, Hans Renata, Russell D Lewis, S B Jennifer Kan, Chen Zhang, Jared Forte, David Rozzell, John A McIntosh, Frances H Arnold
Extending the scope of biocatalysis to important non-natural reactions such as olefin cyclopropanation will open new opportunities for replacing multi-step chemical syntheses of pharmaceutical intermediates with efficient, clean, and highly selective enzyme-catalyzed processes. In this work, we engineered the truncated globin of Bacillus subtilis for the synthesis of a cyclopropane precursor to the antithrombotic agent ticagrelor. The engineered enzyme catalyzes the cyclopropanation of 3,4-difluorostyrene with ethyl diazoacetate on a preparative scale to give ethyl-(1R, 2R)-2-(3,4-difluorophenyl)-cyclopropanecarboxylate in 79% yield, with very high diastereoselectivity (>99% dr) and enantioselectivity (98% ee), enabling a single-step biocatalytic route to this pharmaceutical intermediate...
November 4, 2016: ACS Catalysis
https://www.readbyqxmd.com/read/28283705/s-3-aminobenzanthron-2-yl-cysteine-in-the-globin-of-rats-as-a-novel-type-of-adduct-and-possible-biomarker-of-exposure-to-3-nitrobenzanthrone-a-potent-environmental-carcinogen
#8
Igor Linhart, Iveta Hanzlíková, Jaroslav Mráz, Šárka Dušková
3-Nitrobenzanthrone (3-NBA), a potent environmental mutagen and carcinogen, is known to be activated in vivo to 3-benzanthronylnitrenium ion which forms both NH and C2-bound adducts with DNA and also reacts with glutathione giving rise to urinary 3-aminobenzanthron-2-ylmercapturic acid. In this study, acid hydrolysate of globin from rats dosed intraperitoneally with 3-NBA was analysed by HPLC/MS to identify a novel type of cysteine adduct, 3-aminobenzanthron-2-ylcysteine (3-ABA-Cys), confirmed using a synthesised standard...
March 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28280727/existence-of-hbf-enhancer-haplotypes-at-hbs1l-myb-intergenic-region-in-transfusion-dependent-saudi-%C3%AE-thalassemia-patients
#9
Cyril Cyrus, Chittibabu Vatte, J Francis Borgio, Abdullah Al-Rubaish, Shahanas Chathoth, Zaki A Nasserullah, Sana Al Jarrash, Ahmed Sulaiman, Hatem Qutub, Hassan Alsaleem, Alhusain J Alzahrani, Martin H Steinberg, Amein K Al Ali
Background and Objectives. β-Thalassemia and sickle cell disease are genetic disorders characterized by reduced and abnormal β-globin chain production, respectively. The elevation of fetal hemoglobin (HbF) can ameliorate the severity of these disorders. In sickle cell disease patients, the HbF level elevation is associated with three quantitative trait loci (QTLs), BCL11A, HBG2 promoter, and HBS1L-MYB intergenic region. This study elucidates the existence of the variants in these three QTLs to determine their association with HbF levels of transfusion-dependent Saudi β-thalassemia patients...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28276871/%C3%AE-thalassemia-gene-mutations-in-antalya-turkey-results-from-a-single-centre-study
#10
Ayşegül Kurtoğlu, Volkan Karakuş, Özgür Erkal, Erdal Kurtoğlu
β-Thalassemia (β-thal) is a common autosomal recessive disorder resulting from over 300 different mutations of the β-globin genes. Our aim was to create a mutation map of β-thal in the province of Antalya, Turkey. In this study, mutation analysis of a total 146 of β-thal patients followed at the Thalassemia Center of the Antalya Education and Research Hospital, Antalya, Turkey, were included. Direct DNA sequence analysis was performed for mutation scanning of the β-globin gene. One hundred and forty-six patients with β-thal including all types were analyzed, and 14 different β-thal mutations were detected...
March 3, 2017: Hemoglobin
https://www.readbyqxmd.com/read/28276593/association-between-sickle-cell-anemia-and-alpha-thalassemia-reveals-a-high-prevalence-of-the-%C3%AE-3-7-triplication-in-congolese-patients-than-in-worldwide-series
#11
Tite Minga Mikobi, Prosper Tshilobo Lukusa, Michel Ntetani Aloni, Aimé Lumaka, Pierre Zalagile Akilimali, Koenraad Devriendt, Gert Matthijs, Jean-Marie Mbuyi Muamba, Valerie Race
BACKGROUND: Information about the association with alpha thalassemia in sickle cell patients is unknown in the Democratic Republic of Congo. There is very little data on the alpha thalassemia in patients suffering from sickle cell anemia in Central Africa, and their consequences on the clinical expression of the disease. METHODS: A cross-sectional study was conducted in 106 sickle cell patients living in the country's capital Kinshasa. The diagnosis of sickle cell anemia was confirmed with a molecular test using PCR-RFLP (restriction fragment length polymorphism) technique...
March 9, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28270213/preliminary-survey-on-anopheles-species-distribution-in-botswana-shows-the-presence-of-anopheles-gambiae-and-anopheles-funestus-complexes
#12
Leabaneng Tawe, Pleasure Ramatlho, Kelebogile Waniwa, Charles W Muthoga, Ntebaleng Makate, Davis S Ntebela, Isaac K Quaye, Marco Pombi, Giacomo Maria Paganotti
BACKGROUND: Botswana is one of the four front line malaria elimination countries in Southern Africa, with malaria control activities that include routine vector control. Past and recent studies have shown that Anopheles arabiensis is the only known vector of Plasmodium parasites in the country. This report presents a preliminary evaluation on Anopheles species composition in seven districts of Botswana with some inferences on their vectorial role. RESULTS: Overall, 404 Anopheles mosquito females were collected, of which 196 were larvae collected from several breeding sites, and 208 were adults obtained from indoor pyrethrum spray catches (PSC)...
March 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28267358/rna-trans-splicing-targeting-endogenous-%C3%AE-globin-pre-messenger-rna-in-human-erythroid-cells
#13
Naoya Uchida, Kareem N Washington, Brian Mozer, Charlotte Platner, Josiah Ballantine, Luke P Skala, Lydia Raines, Anna Shvygin, Matthew M Hsieh, Lloyd G Mitchell, John F Tisdale
Sickle cell disease results from a point mutation in exon 1 of the β-globin gene (total 3 exons). Replacing sickle β-globin exon 1 (and exon 2) with a normal sequence by trans-splicing is a potential therapeutic strategy. Therefore, this study sought to develop trans-splicing targeting β-globin pre-messenger RNA among human erythroid cells. Binding domains from random β-globin sequences were comprehensively screened. Six candidates had optimal binding, and all targeted intron 2. Next, lentiviral vectors encoding RNA trans-splicing molecules were constructed incorporating a unique binding domain from these candidates, artificial 5' splice site, and γ-globin cDNA, and trans-splicing was evaluated in CD34(+) cell-derived erythroid cells from healthy individuals...
February 14, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28260494/hemoglobin-and-myoglobin-as-reducing-agents-in-biological-systems-redox-reactions-of-globins-with-copper-and-iron-salts-and-complexes
#14
REVIEW
G B Postnikova, E A Shekhovtsova
In addition to reversible O2 binding, respiratory proteins of the globin family, hemoglobin (Hb) and myoglobin (Mb), participate in redox reactions with various metal complexes, including biologically significant ones, such as those of copper and iron. HbO2 and MbO2 are present in cells in large amounts and, as redox agents, can contribute to maintaining cell redox state and resisting oxidative stress. Divalent copper complexes with high redox potentials (E0, 200-600 mV) and high stability constants, such as [Cu(phen)2](2+), [Cu(dmphen)2](2+), and CuDTA oxidize ferrous heme proteins by the simple outer-sphere electron transfer mechanism through overlapping π-orbitals of the heme and the copper complex...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28259625/characterization-of-the-selective-alkylation-site-in-hemoglobin-a-by-dihydroartemisinin-with-tandem-mass-spectrometry
#15
Khomsan Tiensomjitr, Samran Prabpai, Palangpon Kongsaeree
The reaction between the antimalarial drug dihydroartemisinin (DHA) and hemoglobin A (HbA) was investigated in vitro. A fluorescein-tagged artemisinin analog reacted with HbA and fluorescent HbA-drug adducts could be visualized on SDS-PAGE to confirm stable covalent reaction adducts and necessity of the endoperoxide moiety and Fe(II). Mass spectrometric analyses revealed that DHA favourably alkylated protein part rather than heme and the modification site was identified to be at Tyr35 of the beta globin chain...
March 1, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28251479/changes-in-lncrnas-and-related-genes-in-%C3%AE-thalassemia-minor-and-%C3%AE-thalassemia-major
#16
Jing Ma, Fei Liu, Xin Du, Duan Ma, Likuan Xiong
β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups...
March 2, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28249925/hemoglobin-wayne-trait-with-incidental-polycythemia
#17
Manju Ambelil, Nghia Nguyen, Amitava Dasgupta, Semyon Risin, Amer Wahed
Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain hemoglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28249145/gene-therapy-in-a-patient-with-sickle-cell-disease
#18
Jean-Antoine Ribeil, Salima Hacein-Bey-Abina, Emmanuel Payen, Alessandra Magnani, Michaela Semeraro, Elisa Magrin, Laure Caccavelli, Benedicte Neven, Philippe Bourget, Wassim El Nemer, Pablo Bartolucci, Leslie Weber, Hervé Puy, Jean-François Meritet, David Grevent, Yves Beuzard, Stany Chrétien, Thibaud Lefebvre, Robert W Ross, Olivier Negre, Gabor Veres, Laura Sandler, Sandeep Soni, Mariane de Montalembert, Stéphane Blanche, Philippe Leboulch, Marina Cavazzana
Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning...
March 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28246171/a-distal-ligand-mutes-the-interaction-of-hydrogen-sulfide-with-human-neuroglobin
#19
Markus Ruetz, Jacques Kumutima, Brianne E Lewis, Milos R Filipovic, Nicolai Lehnert, Timothy L Stemmler, Ruma Banerjee
Hydrogen sulfide is a critical signaling molecule, but high concentrations cause cellular toxicity. A four-enzyme pathway in the mitochondrion detoxifies H2S by converting it to thiosulfate and sulfate. Recent studies have shown that globins like hemoglobin and myoglobin can also oxidize H2S to thiosulfate and hydropolysulfides. Neuroglobin, a globin enriched in brain, was reported to bind H2S tightly and postulated to play a role in modulating neuronal sensitivity to H2S in conditions such as stroke. However, the H2S reactivity of the coordinately saturated heme in neuroglobin is expected a priori to be substantially lower than that of the 5-coordinate hemes present in myoglobin and hemoglobin...
February 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28245416/-research-progress-on-thalassemia-in-southern-china-review
#20
Yang Yang, Jie Zhang
Thalassemia is a single-gene disorder resulting from globin chain synthesis impairment because of the mutation or deletion of globin gene, such as α- and β-thalassemia. Thalassemia occurs with high frequencies in tropical and subtropical regions, primarily in Southeast Asian, Middle Eastern, African and Mediterranean populations. It has been reported that thalassemia is prevalent and variable in southern China, including Guangdong, Guangxi, Guizhou, Yunnan and so on. The spectra of globin gene mutations are diverse and characterized by ethnicity and region in southern China...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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