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Circulating nucleosomes

Peter Ulz, Gerhard G Thallinger, Martina Auer, Ricarda Graf, Karl Kashofer, Stephan W Jahn, Luca Abete, Gunda Pristauz, Edgar Petru, Jochen B Geigl, Ellen Heitzer, Michael R Speicher
The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing of plasma DNA and identified two discrete regions at transcription start sites (TSSs) where nucleosome occupancy results in different read depth coverage patterns for expressed and silent genes. By employing machine learning for gene classification, we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells...
October 2016: Nature Genetics
Xavier Delabranche, Laure Stiel, François Severac, Anne-Cécile Galoisy, Laurent Mauvieux, Fatiha Zobairi, Thierry Lavigne, Florence Toti, Eduardo Anglès-Cano, Ferhat Meziani, Julie Boisramé-Helms
INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic-shock induced DIC. METHODS: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study...
August 2, 2016: Shock
Anna Sina P Meyer, Sisse R Ostrowski, Jesper Kjaergaard, Pär I Johansson, Christian Hassager
BACKGROUND: Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery and AMI...
2016: Trials
Ann R Kennedy, Amit Maity, Jenine K Sanzari
Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation...
August 2016: Radiation Research
Irena Orságová, Luděk RoŽnovský, Lenka Petroušová, Michaela Konečná, Libuše Kabieszová, Jan Martinek, Alena Kloudová, Ladislav Pavliska
OBJECTIVE: To determine the prevalence of autoimmune parameters in patients with chronic hepatitis B and C (HBV, HCV) treated with conventional or pegylated interferon alpha (IFN) and monitor the development of autoimmune diseases in connection with this treatment. PATIENTS AND METHODS: In the years 1992-2014, autoimmune parameters were evaluated in 324 patients (271 with HCV, 53 with HBV) treated with IFN at the Department of Infectious Diseases in Ostrava. Prior to, during and after completion of IFN treatment, antinuclear antibodies (ANA), antimitochondrial antibodies (AMA), smooth muscle antibodies (SMA), anti-liver/kidney microsomal antibodies (anti-LKM-1), anti-double-stranded DNA antibodies (anti-ds-DNA), antibodies against granulocytes (ANCA), anti-deoxyribonucleoprotein antibodies (anti-DNP), anti-nucleosomes antibodies, rheumatoid factor (RF) and circulating immune complexes (CIC) were determined and clinical manifestations of autoimmune diseases were evaluated...
June 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
Colin Logie, Hendrik G Stunnenberg
The molecular basis of cellular memory is a fascinating topic that progressed with great strides during the last few decades. In the case of cells of the immune system, cellular memory likely extends beyond cell fate determination mechanisms, since immunity can tailor its responses to a potentially hostile environment that is a priori variable if not unpredictable. One particularly versatile innate immune system cell type is the macrophage. These phagocytes occur in all organs and tissues as resident cells or as differentiation products of recruited circulating blood monocytes...
August 2016: Seminars in Immunology
A R Thierry, S El Messaoudi, P B Gahan, P Anker, M Stroun
While various clinical applications especially in oncology are now in progress such as diagnosis, prognosis, therapy monitoring, or patient follow-up, the determination of structural characteristics of cell-free circulating DNA (cirDNA) are still being researched. Nevertheless, some specific structures have been identified and cirDNA has been shown to be composed of many "kinds." This structural description goes hand-in-hand with the mechanisms of its origins such as apoptosis, necrosis, active release, phagocytosis, and exocytose...
September 2016: Cancer Metastasis Reviews
Ricardo H Pires, Stephan B Felix, Mihaela Delcea
Neutrophils are immune cells that engage in a suicidal pathway leading to the release of partially decondensed chromatin, or neutrophil extracellular traps (NETs). NETs behave as a double edged sword; they can bind to pathogens thereby ensnaring them and limiting their spread during infection; however, they may bind to host circulating materials and trigger thrombotic events, and are associated with autoimmune disorders. Despite the fundamental role of NETs as part of an immune system response, there is currently a very poor understanding of how their nanoscale properties are reflected in their macroscopic impact...
August 7, 2016: Nanoscale
Philip Burnham, Min Seong Kim, Sean Agbor-Enoh, Helen Luikart, Hannah A Valantine, Kiran K Khush, Iwijn De Vlaminck
Circulating cell-free DNA (cfDNA) is emerging as a powerful monitoring tool in cancer, pregnancy and organ transplantation. Nucleosomal DNA, the predominant form of plasma cfDNA, can be adapted for sequencing via ligation of double-stranded DNA (dsDNA) adapters. dsDNA library preparations, however, are insensitive to ultrashort, degraded cfDNA. Drawing inspiration from advances in paleogenomics, we have applied a single-stranded DNA (ssDNA) library preparation method to sequencing of cfDNA in the plasma of lung transplant recipients (40 samples, six patients)...
2016: Scientific Reports
Louise Rasmussen, Marielle Herzog, Eva Rømer, Jake Micallef, Orhan Bulut, Michael Wilhelmsen, Ib Jarle Christensen, Hans J Nielsen
AIM: To evaluate pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA (5mC) or histone modification H3K9Me3 (H3K9Me3). MATERIALS AND METHODS: Six studies were designed to assess the possible influence of pre-analytical variables. Study 1: influence of stasis and contamination with white-cells and platelets. Study 2: influence of within-day variations. Study 3: influence of day-to-day variation. Study 4: influence of temperature during handling and storage, and of neoplastic disease...
October 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Maria Victoria Ramos, Maria Pilar Mejias, Florencia Sabbione, Romina Jimena Fernandez-Brando, Adriana Patricia Santiago, Maria Marta Amaral, Ramon Exeni, Analia Silvina Trevani, Marina Sandra Palermo
Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN can release neutrophil extracellular traps (NET) composed of DNA, histones, and other proteins. Since NET are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NET to HUS...
2016: Journal of Innate Immunity
Nadir Yehya, Neal J Thomas, Susan S Margulies
Mechanisms underlying pediatric acute respiratory distress syndrome (PARDS) are poorly understood. The recent implication of circulating nucleosomes as pathogenic in sepsis and trauma-associated ARDS in adults led us to investigate the significance of nucleosomes in PARDS. We conducted a prospective, observational study on children with PARDS at the Children's Hospital of Philadelphia between July 2014 and September 2015. Plasma was collected within 48 h of PARDS onset and nucleosomes quantified by enzyme-linked immunosorbent assay...
June 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Anne K Penttilä, Ari Rouhiainen, Leena Kylänpää, Harri Mustonen, Pauli Puolakkainen, Heikki Rauvala, Heikki Repo
BACKGROUND: The components of nucleosomes, which contain DNA and histones, are released into the circulation from damaged cells and can promote inflammation. We studied whether the on-admission levels of circulating nucleosomes predict the development of severe acute pancreatitis (AP), in particular among the patients who present without clinical signs of organ dysfunction. METHODS: This is a prospective study of 74 AP patients admitted to Helsinki University Hospital from 2003 to 2007...
2016: Journal of Intensive Care
Ugur Gezer, Ebru E Yörüker, Metin Keskin, Cemil Burak Kulle, Yoganiranjana Dharuman, Stefan Holdenrieder
Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes...
2015: International Journal of Molecular Sciences
Jakub Závada, Michal Uher, Radka Svobodová, Marta Olejárová, Markéta Hušáková, Hana Ciferská, Hana Hulejová, Michal Tomčík, Ladislav Šenolt, Jiří Vencovský
INTRODUCTION: The aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE). METHODS: Serum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3-6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially...
2015: Arthritis Research & Therapy
S H Nymo, T Ueland, E Askevold, C P Dahl, L Gullestad, P Aukrust, A Yndestad
No abstract text is available yet for this article.
January 15, 2016: International Journal of Cardiology
Hanna D Bremer, Erik Lattwein, Stefanie Renneker, Inger Lilliehöök, Johan Rönnelid, Helene Hansson-Hamlin
Circulating antinuclear antibodies (ANA) are commonly present in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) and in other systemic rheumatic diseases, in humans as well as in dogs. The indirect immunofluorescence (IIF)-ANA test is the standard method for detecting ANA. Further testing for specific ANA with immunoblot techniques or ELISAs is routinely performed in humans to aid in the diagnosis and monitoring of disease. Several specific ANA identified in humans have been identified also in suspected canine SLE but, in contrast to humans, investigation of autoantibodies in canine SLE is mainly restricted to the IIF-ANA test...
December 15, 2015: Veterinary Immunology and Immunopathology
Robert A McKnight, Christian C Yost, Xing Yu, Julia E Wiedmeier, Christopher W Callaway, Ashley S Brown, Robert H Lane, Camille M Fung
Intrauterine growth restriction (IUGR) is a common human pregnancy complication. IUGR offspring carry significant postnatal risk for early-onset metabolic syndrome, which is associated with persistent reduction in IGF-1 protein expression. We have previously shown that preadolescent IUGR male mice have decreased hepatic IGF-1 mRNA and circulating IGF-1 protein at postnatal day 21, the age when growth hormone (GH) normally upregulates hepatic IGF-1 expression. Here we studied nucleosome occupancy and CpG methylation at a putative growth hormone-responsive element in intron 2 (in2GHRE) of the hepatic IGF-1 gene in normal, sham-operated, and IUGR mice...
December 2015: Physiological Genomics
Raymond Liang, Genís Campreciós, Yan Kou, Kathleen McGrath, Roberta Nowak, Seana Catherman, Carolina L Bigarella, Pauline Rimmelé, Xin Zhang, Merlin Nithya Gnanapragasam, James J Bieker, Dmitri Papatsenko, Avi Ma'ayan, Emery Bresnick, Velia Fowler, James Palis, Saghi Ghaffari
Circulating red blood cells (RBCs) are essential for tissue oxygenation and homeostasis. Defective terminal erythropoiesis contributes to decreased generation of RBCs in many disorders. Specifically, ineffective nuclear expulsion (enucleation) during terminal maturation is an obstacle to therapeutic RBC production in vitro. To obtain mechanistic insights into terminal erythropoiesis we focused on FOXO3, a transcription factor implicated in erythroid disorders. Using an integrated computational and experimental systems biology approach, we show that FOXO3 is essential for the correct temporal gene expression during terminal erythropoiesis...
October 2015: PLoS Genetics
Monika Bauden, Dorian Pamart, Daniel Ansari, Marielle Herzog, Mark Eccleston, Jake Micallef, Bodil Andersson, Roland Andersson
BACKGROUND: To improve the prognosis of patients with pancreatic cancer, new biomarkers are required for earlier, pre-symptomatic diagnosis. Epigenetic mutations take place at the earliest stages of tumorigenesis and therefore offer new approaches for detecting and diagnosing disease. Nucleosomes are the repeating subunits of DNA and histone proteins that constitute human chromatin. Because of their release into the circulation, intact nucleosome levels in serum or plasma can serve as diagnostic disease biomarkers, and elevated levels have been reported in various cancers...
2015: Clinical Epigenetics
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