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  1. Article ; Online: Residual risks and evolving atherosclerotic plaques.

    Noothi, Sunil K / Ahmed, Mohamed Radwan / Agrawal, Devendra K

    Molecular and cellular biochemistry

    2023  Volume 478, Issue 12, Page(s) 2629–2643

    Abstract: Atherosclerotic disease of the coronary and carotid arteries is the primary global cause of significant mortality and morbidity. The chronic occlusive diseases have changed the epidemiological landscape of health problems both in developed and the ... ...

    Abstract Atherosclerotic disease of the coronary and carotid arteries is the primary global cause of significant mortality and morbidity. The chronic occlusive diseases have changed the epidemiological landscape of health problems both in developed and the developing countries. Despite the enormous benefit of advanced revascularization techniques, use of statins, and successful attempts of targeting modifiable risk factors, like smoking and exercise in the last four decades, there is still a definite "residual risk" in the population, as evidenced by many prevalent and new cases every year. Here, we highlight the burden of the atherosclerotic diseases and provide substantial clinical evidence of the residual risks in these diseases despite advanced management settings, with emphasis on strokes and cardiovascular risks. We critically discussed the concepts and potential underlying mechanisms of the evolving atherosclerotic plaques in the coronary and carotid arteries. This has changed our understanding of the plaque biology, the progression of unstable vs stable plaques, and the evolution of plaque prior to the occurrence of a major adverse atherothrombotic event. This has been facilitated using intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the clinical settings to achieve surrogate end points. These techniques are now providing exquisite information on plaque size, composition, lipid volume, fibrous cap thickness and other features that were previously not possible with conventional angiography.
    MeSH term(s) Humans ; Plaque, Atherosclerotic ; Atherosclerosis ; Carotid Arteries ; Stroke ; Risk Factors ; Coronary Artery Disease/epidemiology
    Language English
    Publishing date 2023-03-10
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 184833-1
    ISSN 1573-4919 ; 0300-8177
    ISSN (online) 1573-4919
    ISSN 0300-8177
    DOI 10.1007/s11010-023-04689-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Role of the splenic microenvironment in chronic lymphocytic leukemia development in Eµ-TCL1 transgenic mice.

    Collard, James P / McKenna, Mary K / Noothi, Sunil K / Alhakeem, Sara S / Rivas, Jacqueline R / Rangnekar, Vivek M / Muthusamy, Natarajan / Bondada, Subbarao

    Leukemia & lymphoma

    2022  Volume 63, Issue 8, Page(s) 1810–1822

    Abstract: The chronic lymphocytic leukemia (CLL) microenvironment has been receiving an increasing amount of attention, but there is currently limited data surrounding how the microenvironment affects initial development of CLL. We determined that the spleen is ... ...

    Abstract The chronic lymphocytic leukemia (CLL) microenvironment has been receiving an increasing amount of attention, but there is currently limited data surrounding how the microenvironment affects initial development of CLL. We determined that the spleen is the initial site of CLL growth through monitoring of transgenic Eμ-TCL1 mice that develop CLL. Subsequently, we isolated stromal cells from the spleens of Eμ-TCL1 mice (EMST cells) that induce CLL cell division
    MeSH term(s) Animals ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Mice ; Mice, Transgenic ; Proto-Oncogene Proteins ; Spleen ; Stromal Cells ; Tumor Microenvironment
    Chemical Substances Proto-Oncogene Proteins ; Tcl1 protein, mouse
    Language English
    Publishing date 2022-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2022.2045596
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: It's reticulated: the liver at the heart of atherosclerosis.

    Nagareddy, Prabhakara R / Noothi, Sunil K / Flynn, Michelle C / Murphy, Andrew J

    The Journal of endocrinology

    2018  Volume 238, Issue 1, Page(s) R1–R11

    Abstract: Platelets play a critical role in both the initiation and progression of atherosclerosis, and even more so in the ensuing atherothrombotic complications. Low-dose aspirin remains the mainstay of antiplatelet therapy in high-risk patients by reducing the ... ...

    Abstract Platelets play a critical role in both the initiation and progression of atherosclerosis, and even more so in the ensuing atherothrombotic complications. Low-dose aspirin remains the mainstay of antiplatelet therapy in high-risk patients by reducing the risk of myocardial ischemia, stroke or death due to cardiovascular disease. However, antiplatelet therapies lose their efficacy in people with diabetes mellitus, increasing the risk of future atherothrombotic events. The molecular mechanisms that promote platelet hyperactivity remain unclear but could be due to glycation-induced conformational changes of platelet membranes resulting in impaired aspirin entry or less-efficient acetylation/compensatory increase in COX-2 expression in newborn platelets. Emerging evidence from our laboratory and elsewhere suggest that enhanced platelet turnover (thrombopoiesis), particularly the production of immature reticulated platelets from the bone marrow, could contribute to atherosclerotic complications. We have identified a major role for neutrophil-derived S100A8/A9, a damage-associated molecular pattern, in driving reticulated thrombopoiesis by directly interacting with its receptors on Kupffer cells in the liver. In this review, we discuss the role of hepatic inflammation in driving reticulated platelet production and suggest potential targets to control their production, improve efficacy of current antiplatelet therapies and reduce the risk of atherothrombotic complications.
    MeSH term(s) Animals ; Aspirin/therapeutic use ; Atherosclerosis/drug therapy ; Atherosclerosis/etiology ; Atherosclerosis/pathology ; Atherosclerosis/physiopathology ; Blood Platelets/drug effects ; Blood Platelets/physiology ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/physiology ; Hepatitis/complications ; Hepatitis/pathology ; Hepatitis/physiopathology ; Humans ; Infant, Newborn ; Liver/drug effects ; Liver/pathology ; Liver/physiology ; Myelopoiesis/drug effects ; Myelopoiesis/physiology ; Risk Factors ; Thrombopoiesis/drug effects ; Thrombopoiesis/physiology ; Treatment Outcome
    Chemical Substances Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2018-05-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-18-0082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterizing the Retinal Phenotype in the High-Fat Diet and Western Diet Mouse Models of Prediabetes.

    Asare-Bediako, Bright / Noothi, Sunil K / Li Calzi, Sergio / Athmanathan, Baskaran / Vieira, Cristiano P / Adu-Agyeiwaah, Yvonne / Dupont, Mariana / Jones, Bryce A / Wang, Xiaoxin X / Chakraborty, Dibyendu / Levi, Moshe / Nagareddy, Prabhakara R / Grant, Maria B

    Cells

    2020  Volume 9, Issue 2

    Abstract: We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on ... ...

    Abstract We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g,
    MeSH term(s) Animals ; Body Weight ; Diabetes Mellitus, Type 2/physiopathology ; Diabetic Retinopathy/physiopathology ; Diet, Fat-Restricted ; Diet, High-Fat ; Diet, Western ; Disease Models, Animal ; Electroretinography ; Insulin Resistance ; Mice ; Mice, Inbred C57BL ; Obesity/physiopathology ; Phenotype ; Prediabetic State/physiopathology ; Retina/physiopathology
    Language English
    Publishing date 2020-02-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9020464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity.

    Araujo, Nathalia / Sledziona, James / Noothi, Sunil K / Burikhanov, Ravshan / Hebbar, Nikhil / Ganguly, Saptadwipa / Shrestha-Bhattarai, Tripti / Zhu, Beibei / Katz, Wendy S / Zhang, Yi / Taylor, Barry S / Liu, Jinze / Chen, Li / Weiss, Heidi L / He, Daheng / Wang, Chi / Morris, Andrew J / Cassis, Lisa A / Nikolova-Karakashian, Mariana /
    Nagareddy, Prabhakar R / Melander, Olle / Evers, B Mark / Kern, Philip A / Rangnekar, Vivek M

    Frontiers in oncology

    2022  Volume 12, Page(s) 860446

    Abstract: Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par- ... ...

    Abstract Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4
    Language English
    Publishing date 2022-03-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.860446
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: MutS and UvrD proteins stimulate exonuclease action: insights into exonuclease-mediated strand repair.

    Noothi, Sunil K / Minda, Renu / Rao, Basuthkar J

    Biochemistry

    2009  Volume 48, Issue 33, Page(s) 7787–7793

    Abstract: MutS and UvrD proteins individually stimulate Escherichia coli exonuclease VII activity on blunt-ended short duplex DNA substrates. Stimulation by both proteins is ATP-dependent but not mismatch-specific and is not accompanied by apparent strand ... ...

    Abstract MutS and UvrD proteins individually stimulate Escherichia coli exonuclease VII activity on blunt-ended short duplex DNA substrates. Stimulation by both proteins is ATP-dependent but not mismatch-specific and is not accompanied by apparent strand separation. Under similar conditions, MutS and UvrD proteins in fact confer resistance to exonuclease VII action on ssDNA targets, thereby implying that a novel state of a double-stranded DNA intermediate, which we term a "destabilized duplex", is involved in exonuclease-mediated strand degradation. We find that DNA strands in such a destabilized duplex can be displaced by the challenge of a molar excess of homologous single- and double-stranded DNA targets, in trans. Such an action of the UvrD protein is ATP-dependent. We discuss these results in relation to the (i) directional excision repair of E. coli MMR, (ii) downregulation of repeat deletions by exonucleases during replication slippage, and (iii) the fork reversal function of UvrD at stalled replication forks.
    MeSH term(s) Base Pairing/genetics ; DNA Helicases/chemistry ; DNA Helicases/genetics ; DNA Mismatch Repair/genetics ; DNA, Bacterial/chemistry ; DNA, Bacterial/genetics ; Drug Resistance, Bacterial ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Exodeoxyribonucleases/chemistry ; Exodeoxyribonucleases/genetics ; MutS DNA Mismatch-Binding Protein/chemistry ; MutS DNA Mismatch-Binding Protein/genetics ; Nucleic Acid Heteroduplexes/chemistry ; Nucleic Acid Heteroduplexes/genetics ; Repetitive Sequences, Nucleic Acid ; Tandem Repeat Sequences/genetics
    Chemical Substances DNA, Bacterial ; Escherichia coli Proteins ; Nucleic Acid Heteroduplexes ; Exodeoxyribonucleases (EC 3.1.-) ; exodeoxyribonuclease VII (EC 3.1.11.6) ; UvrD protein, E coli (EC 3.6.1.-) ; MutS DNA Mismatch-Binding Protein (EC 3.6.1.3) ; MutS protein, E coli (EC 3.6.1.3) ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2009-08-25
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/bi8020313
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity.

    Alhakeem, Sara S / McKenna, Mary K / Oben, Karine Z / Noothi, Sunil K / Rivas, Jacqueline R / Hildebrandt, Gerhard C / Fleischman, Roger A / Rangnekar, Vivek M / Muthusamy, Natarajan / Bondada, Subbarao

    Journal of immunology (Baltimore, Md. : 1950)

    2018  Volume 200, Issue 12, Page(s) 4180–4189

    Abstract: Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross- ... ...

    Abstract Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross-linking. We used the transgenic Eμ-T cell leukemia oncogene-1 (
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes/immunology ; Cell Proliferation/physiology ; Disease Models, Animal ; Humans ; Interleukin-10/immunology ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Proto-Oncogene Proteins/immunology ; Signal Transduction/immunology
    Chemical Substances IL10 protein, mouse ; Proto-Oncogene Proteins ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2018-04-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1800241
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Fluorescence characterization of the structural heterogeneity of polytene chromosomes.

    Noothi, Sunil K / Kombrabail, Mamata / Rao, Basuthkar J / Krishnamoorthy, G

    Journal of fluorescence

    2009  Volume 20, Issue 1, Page(s) 37–41

    Abstract: Studies on the physical nature of the structural heterogeneity of chromatin in their native states are few. The eukaryotic chromatin as observed by dye staining studies is of heterogeneous intensity when observed by fluorescent stains, where less and ... ...

    Abstract Studies on the physical nature of the structural heterogeneity of chromatin in their native states are few. The eukaryotic chromatin as observed by dye staining studies is of heterogeneous intensity when observed by fluorescent stains, where less and more bright regions apparently correspond to euchromatin and heterochromatin respectively. These are also associated with differential gene expression where it is believed that euchromatin is transcriptionally more active due to increased flexibility. Unfixed squashed preparations of polytene chromosomes of Drosophila were stained with a dsDNA specific dye PicoGreen and fluorescence lifetimes as well as fluorescence anisotropy decay kinetics were measured. Here we report a positive correlation between fluorescence lifetimes and fluorescence intensities, and show that less bright regions corresponding to euchromatin have shorter lifetimes, whereas more bright regions corresponding to heterochromatin have longer lifetimes. We interpret this as less bright regions being more dynamic, a conclusion also supported by fluorescence anisotropy decay kinetics. We infer that the comparatively higher flexibility associated with euchromatin can be directly measured by fluorescence lifetimes and fluorescence anisotropy decay kinetics.
    MeSH term(s) Animals ; Chromatin/chemistry ; Chromatin/metabolism ; Chromosomes/chemistry ; Chromosomes/metabolism ; Drosophila melanogaster/cytology ; Fluorescence Polarization ; Fluorescent Dyes/metabolism ; Kinetics ; Microscopy, Fluorescence ; Organic Chemicals/metabolism
    Chemical Substances Chromatin ; Fluorescent Dyes ; Organic Chemicals ; PicoGreen
    Language English
    Publishing date 2009-07-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2016892-5
    ISSN 1573-4994 ; 1053-0509
    ISSN (online) 1573-4994
    ISSN 1053-0509
    DOI 10.1007/s10895-009-0519-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Neutrophil-Derived S100A8/A9 Amplify Granulopoiesis After Myocardial Infarction.

    Sreejit, Gopalkrishna / Abdel-Latif, Ahmed / Athmanathan, Baskaran / Annabathula, Rahul / Dhyani, Ashish / Noothi, Sunil K / Quaife-Ryan, Gregory A / Al-Sharea, Annas / Pernes, Gerard / Dragoljevic, Dragana / Lal, Hind / Schroder, Kate / Hanaoka, Beatriz Y / Raman, Chander / Grant, Maria B / Hudson, James E / Smyth, Susan S / Porrello, Enzo R / Murphy, Andrew J /
    Nagareddy, Prabhakara R

    Circulation

    2020  Volume 141, Issue 13, Page(s) 1080–1094

    Abstract: Background: Myocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.: Methods: Using a mouse model of ... ...

    Abstract Background: Myocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.
    Methods: Using a mouse model of the permanent ligation of the left anterior descending artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of the acute inflammatory response and the underlying signaling pathways. Using a combination of genetic and pharmacological strategies, we identified the sequelae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indexes of neutrophilia with major adverse cardiovascular events was studied in a cohort of patients with acute MI.
    Results: Induction of MI results in rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll-like receptor 4 and prime the nod-like receptor family pyrin domain-containing 3 inflammasome in naïve neutrophils and promote interleukin-1β secretion. The released interleukin-1β interacts with its receptor (interleukin 1 receptor type 1) on hematopoietic stem and progenitor cells in the bone marrow and stimulates granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and their downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome, higher neutrophil count on admission and after revascularization correlates positively with major adverse cardiovascular disease outcomes.
    Conclusions: Our study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response after myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or their downstream mediators (eg, nod-like receptor family pyrin domain-containing 3 inflammasome, interleukin-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in patients with acute coronary syndrome.
    MeSH term(s) Animals ; Calgranulin A/metabolism ; Disease Models, Animal ; Female ; Granulocytes/metabolism ; Humans ; Male ; Mice ; Myocardial Infarction/blood ; Neutrophils/metabolism
    Chemical Substances Calgranulin A ; S100A8 protein, human
    Language English
    Publishing date 2020-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.119.043833
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Enhanced DNA dynamics due to cationic reagents, topological states of dsDNA and high mobility group box 1 as probed by PicoGreen

    Noothi, Sunil K / Kombrabail, Mamata / Kundu, Tapas K / Krishnamoorthy, G / Rao, Basuthkar J

    FEBS journal. 2009 Jan., v. 276, no. 2

    2009  

    Abstract: We report a study of dynamics with a dsDNA-specific dye called PicoGreen bound to plasmid DNA (3.4 kb), and show that at low dye/DNA phosphate ratios (1 : 100 and below), PicoGreen dynamics reflect the motional dynamics of dsDNA. We further evaluated the ...

    Abstract We report a study of dynamics with a dsDNA-specific dye called PicoGreen bound to plasmid DNA (3.4 kb), and show that at low dye/DNA phosphate ratios (1 : 100 and below), PicoGreen dynamics reflect the motional dynamics of dsDNA. We further evaluated the usefulness of this probe by measuring the time-resolved fluorescence dynamics of PicoGreen bound to dsDNA in the presence of cationic reagents that affect DNA dynamics [MgCl₂ and polyethyleneimine (PEI)] and also with plasmid DNA in different topological states. Among these conditions, MgCl₂, PEI and the supercoiled form of plasmid resulted in increases in the very short component (0.2-0.4 ns) of the rotational correlation time. Separately, HMGB1 protein enhanced DNA dynamics, as observed from the rotational correlation times of very short (0.2-0.4 ns) and short (2-4 ns) rotational correlation timescale components. By studying the effect of specific deletion mutants HMGB1-ΔA (deletion of 98 N-terminal amino acids) and HMGB1-ΔC (deletion of 30 C-terminal amino acids), we show that the acidic C-terminal tail is required for enhancement of DNA dynamics. We then discuss the possible mechanisms and implications of HMGB1-mediated flexibility of DNA in the context of formation of large nucleoprotein complexes.
    Language English
    Dates of publication 2009-01
    Size p. 541-551.
    Publisher Blackwell Publishing Ltd
    Publishing place Oxford, UK
    Document type Article
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/j.1742-4658.2008.06802.x
    Database NAL-Catalogue (AGRICOLA)

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