Supra-physiological doses of testosterone affect membrane oxidation of human neutrophils monitored by the fluorescent probe C11-BODIPY581/591

The purpose of this study was to determine the effects of supra-physiological doses of testosterone (TES) on membrane oxidation of activated human neutrophils in vitro using an innovative and sensitive technique: the real-time detection with the fluorescence probe C11-BODIPY581/591. Methodological controls were performed with the lipid-soluble and powerful antioxidant astaxanthin at different neutrophil density cultures. Neutrophils from nine healthy young men (23.4 ± 2.5 years, 174.4 ± 7.0 cm height, and 78.3 ± 7.0 kg weight) were isolated and treated with 0.1 or 10 μM TES for 24 h and subsequently labeled with the free radical-sensitive probe C11-BODIPY581/591 for monitoring membrane oxidation after neutrophil activation with phorbol-12-myristate-13-acetate (PMA). First-order exponential decay kinetic indicated that both 0.1 and 10 μM TES severely increased baseline membrane oxidation in non-activated human neutrophils (compared to control). However, similar kinetics of membrane oxidation were observed in control and 0.1 μM TES-treated neutrophils after PMA activation, whereas chemical activation did not alter the baseline higher rates of membrane oxidation in 10 μM TES-treated neutrophils. The data presented here support the hypothesis that TES exerts distinct effects on the membrane oxidation of human neutrophils, depending on its dose (here, 102 to 104-fold higher than physiological levels in men) and on PMA activation of the oxidative burst. Furthermore, this paper also presents an innovative application of the free radical-sensitive probe C11-BODIPY581/591 for monitoring (auto-induced) membrane oxidation as an important parameter of viability and, thus, responsiveness of immune cells in inflammatory processes

Supra-physiological doses of testosterone affect membrane oxidation of human neutrophils monitored by the fluorescent probe C11-BODIPY581/591

The purpose of this study was to determine the effects of supra-physiological doses of testosterone (TES) on membrane oxidation of activated human neutrophils in vitro using an innovative and sensitive technique: the real-time detection with the fluorescence probe C11-BODIPY581/591. Methodological controls were performed with the lipid-soluble and powerful antioxidant astaxanthin at different neutrophil density cultures. Neutrophils from nine healthy young men (23.4 ± 2.5 years, 174.4 ± 7.0 cm height, and 78.3 ± 7.0 kg weight) were isolated and treated with 0.1 or 10 μM TES for 24 h and subsequently labeled with the free radical-sensitive probe C11-BODIPY581/591 for monitoring membrane oxidation after neutrophil activation with phorbol-12-myristate-13-acetate (PMA). First-order exponential decay kinetic indicated that both 0.1 and 10 μM TES severely increased baseline membrane oxidation in non-activated human neutrophils (compared to control). However, similar kinetics of membrane oxidation were observed in control and 0.1 μM TES-treated neutrophils after PMA activation, whereas chemical activation did not alter the baseline higher rates of membrane oxidation in 10 μM TES-treated neutrophils. The data presented here support the hypothesis that TES exerts distinct effects on the membrane oxidation of human neutrophils, depending on its dose (here, 102 to 104-fold higher than physiological levels in men) and on PMA activation of the oxidative burst. Furthermore, this paper also presents an innovative application of the free radical-sensitive probe C11-BODIPY581/591 for monitoring (auto-induced) membrane oxidation as an important parameter of viability and, thus, responsiveness of immune cells in inflammatory processes

Group II Introns Break New Boundaries: Presence in a Bilaterian's Genome

Group II introns are ribozymes, removing themselves from their primary transcripts, as well as mobile genetic elements, transposing via an RNA intermediate, and are thought to be the ancestors of spliceosomal introns. Although common in bacteria and most eukaryotic organelles, they have never been reported in any bilaterian animal genome, organellar or nuclear. Here we report the first group II intron found in the mitochondrial genome of a bilaterian worm. This location is especially surprising, since animal mitochondrial genomes are generally distinct from those of plants, fungi, and protists by being small and compact, and so are viewed as being highly streamlined, perhaps as a result of strong selective pressures for fast replication while establishing germ plasm during early development. This intron is found in the mtDNA of an annelid worm, (an undescribed species of Nephtys), where the complete sequence revealed a 1819 bp group II intron inside the cox1 gene. We infer that this intron is the result of a recent horizontal gene transfer event from a viral or bacterial vector into the mitochondrial genome of Nephtys sp. Our findings hold implications for understanding mechanisms, constraints, and selective pressures that account for patterns of animal mitochondrial genome evolutio

DH and JH usage in murine fetal liver mirrors that of human fetal liver

In mouse and human, the regulated development of antibody repertoire diversity during ontogeny proceeds in parallel with the development of the ability to generate antibodies to an array of specific antigens. Compared to adult, the human fetal antibody repertoire limits N addition and uses specifically positioned VDJ gene segments more frequently, including V6-1 the most DH-proximal VH, DQ52, the most JH-proximal DH, and JH2, which is DH-proximal. The murine fetal antibody repertoire also limits the incorporation of N nucleotides and uses its most DH proximal VH, VH81X, more frequently. To test whether DH and JH also follow the pattern observed in human, we used the scheme of Hardy to sort B lineage cells from BALB/c fetal and neonatal liver, RT-PCR cloned and sequenced VH7183-containing VDJCμ transcripts, and then assessed VH7183-DH-JH and complementary determining region 3 of the immunoglobulin heavy chain (CDR-H3) content in comparison to the previously studied adult BALB/c mouse repertoire. Due to the deficiency in N nucleotide addition, perinatal CDR-H3s manifested a distinct pattern of amino acid usage and predicted loop structures. As in the case of adult bone marrow, we observed a focusing of CDR-H3 length and CDR-H3 loop hydrophobicity, especially in the transition from the early to late pre-B cell stage, a developmental checkpoint associated with expression of the pre-B cell receptor. However, fetal liver usage of JH-proximal DHQ52 and DH-proximal JH2 was markedly greater than that of adult bone marrow. Thus, the early pattern of DH and JH usage in mouse feta liver mirrors that of human

T2K neutrino flux prediction

cited By 15 art_number: 012001 affiliation: Centre for Particle Physics, Department of Physics, University of Alberta, Edmonton, AB, Canada; Albert Einstein Center for Fundamental Physics, Laboratory for High Energy Physics (LHEP), University of Bern, Bern, Switzerland; Department of Physics, Boston University, Boston, MA, United States; Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Physics and Astronomy, University of California Irvine, Irvine, CA, United States; IRFU, CEA Saclay, Gif-sur-Yvette, France; Institute for Universe and Elementary Particles, Chonnam National University, Gwangju, South Korea; Department of Physics, University of Colorado at Boulder, Boulder, CO, United States; Department of Physics, Colorado State University, Fort Collins, CO, United States; Department of Physics, Dongshin University, Naju, South Korea; Department of Physics, Duke University, Durham, NC, United States; IN2P3-CNRS, Laboratoire Leprince-Ringuet, Ecole Polytechnique, Palaiseau, France; Institute for Particle Physics, ETH Zurich, Zurich, Switzerland; Section de Physique, DPNC, University of Geneva, Geneva, Switzerland; H. Niewodniczanski Institute of Nuclear Physics PAN, Cracow, Poland; High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki, Japan; Institut de Fisica d’Altes Energies (IFAE), Bellaterra (Barcelona), Spain; IFIC (CSIC and University of Valencia), Valencia, Spain; Department of Physics, Imperial College London, London, United Kingdom; INFN Sezione di Bari, Dipartimento Interuniversitario di Fisica, Università e Politecnico di Bari, Bari, Italy; INFN Sezione di Napoli and Dipartimento di Fisica, Università di Napoli, Napoli, Italy; INFN Sezione di Padova, Dipartimento di Fisica, Università di Padova, Padova, Italy; INFN Sezione di Roma, Università di Roma la Sapienza, Roma, Italy; Institute for Nuclear Research, Russian Academy of Sciences, Moscow, Russian Federation; Kobe University, Kobe, Japan; Department of Physics, Kyoto University, Kyoto, Japan; Physics Department, Lancaster University, Lancaster, United Kingdom; Department of Physics, University of Liverpool, Liverpool, United Kingdom; Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, United States; Université de Lyon, Université Claude Bernard Lyon 1, IPN Lyon (IN2P3), Villeurbanne, France; Department of Physics, Miyagi University of Education, Sendai, Japan; National Centre for Nuclear Research, Warsaw, Poland; State University of New York at Stony Brook, Stony Brook, NY, United States; Department of Physics and Astronomy, Osaka City University, Department of Physics, Osaka, Japan; Department of Physics, Oxford University, Oxford, United Kingdom; UPMC, Université Paris Diderot, Laboratoire de Physique Nucléaire et de Hautes Energies (LPNHE), Paris, France; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA, United States; School of Physics, Queen Mary University of London, London, United Kingdom; Department of Physics, University of Regina, Regina, SK, Canada; Department of Physics and Astronomy, University of Rochester, Rochester, NY, United States; III. Physikalisches Institut, RWTH Aachen University, Aachen, Germany; Department of Physics and Astronomy, Seoul National University, Seoul, South Korea; Department of Physics and Astronomy, University of Sheffield, Sheffield, United Kingdom; University of Silesia, Institute of Physics, Katowice, Poland; STFC, Rutherford Appleton Laboratory, Harwell Oxford, Warrington, United Kingdom; Department of Physics, University of Tokyo, Tokyo, Japan; Institute for Cosmic Ray Research, Kamioka Observatory, University of Tokyo, Kamioka, Japan; Institute for Cosmic Ray Research, Research Center for Cosmic Neutrinos, University of Tokyo, Kashiwa, Japan; Department of Physics, University of Toronto, Toronto, ON, Canada; TRIUMF, Vancouver, BC, Canada; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada; Faculty of Physics, University of Warsaw, Warsaw, Poland; Institute of Radioelectronics, Warsaw University of Technology, Warsaw, Poland; Department of Physics, University of Warwick, Coventry, United Kingdom; Department of Physics, University of Washington, Seattle, WA, United States; Department of Physics, University of Winnipeg, Winnipeg, MB, Canada; Faculty of Physics and Astronomy, Wroclaw University, Wroclaw, Poland; Department of Physics and Astronomy, York University, Toronto, ON, Canada references: Astier, P., (2003) Nucl. 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The Role of Humoral Innate Immunity in Hepatitis C Virus Infection

Infection with Hepatitis C Virus (HCV) causes chronic disease in approximately 80% of cases, resulting in chronic inflammation and cirrhosis. Current treatments are not completely effective, and a vaccine has yet to be developed. Spontaneous resolution of infection is associated with effective host adaptive immunity to HCV, including production of both HCV-specific T cells and neutralizing antibodies. However, the supporting role of soluble innate factors in protection against HCV is less well understood. The innate immune system provides an immediate line of defense against infections, triggering inflammation and playing a critical role in activating adaptive immunity. Innate immunity comprises both cellular and humoral components, the humoral arm consisting of pattern recognition molecules such as complement C1q, collectins and ficolins. These molecules activate the complement cascade, neutralize pathogens, and recruit antigen presenting cells. Here we review the current understanding of anti-viral components of the humoral innate immune system that play a similar role to antibodies, describing their role in immunity to HCV and their potential contribution to HCV pathogenesis