scholarly journals Molecular Factors of Hypochlorite Tolerance in the Hypersaline Archaeon Haloferax volcanii

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 562 ◽  
Author(s):  
Miguel Gomez ◽  
Whinkie Leung ◽  
Swathi Dantuluri ◽  
Alexander Pillai ◽  
Zyan Gani ◽  
...  
Keyword(s):  
Hypochlorous Acid ◽  
Insertion Site ◽  
Model Organism ◽  
Halophilic Archaea ◽  
Haloferax Volcanii ◽  
Polyamine Biosynthesis ◽  
Active Compounds ◽  
Redox Active ◽  
High Concentrations ◽  
High Doses

Halophilic archaea thrive in hypersaline conditions associated with desiccation, ultraviolet (UV) irradiation and redox active compounds, and thus are naturally tolerant to a variety of stresses. Here, we identified mutations that promote enhanced tolerance of halophilic archaea to redox-active compounds using Haloferax volcanii as a model organism. The strains were isolated from a library of random transposon mutants for growth on high doses of sodium hypochlorite (NaOCl), an agent that forms hypochlorous acid (HOCl) and other redox acid compounds common to aqueous environments of high concentrations of chloride. The transposon insertion site in each of twenty isolated clones was mapped using the following: (i) inverse nested two-step PCR (INT-PCR) and (ii) semi-random two-step PCR (ST-PCR). Genes that were found to be disrupted in hypertolerant strains were associated with lysine deacetylation, proteasomes, transporters, polyamine biosynthesis, electron transfer, and other cellular processes. Further analysis revealed a ΔpsmA1 (α1) markerless deletion strain that produces only the α2 and β proteins of 20S proteasomes was hypertolerant to hypochlorite stress compared with wild type, which produces α1, α2, and β proteins. The results of this study provide new insights into archaeal tolerance of redox active compounds such as hypochlorite.

scholarly journals To Divide or Not to Divide? How Deuterium Affects Growth and Division of Chlamydomonas reinhardtii

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 861
Author(s):  
Veronika Kselíková ◽  
Vilém Zachleder ◽  
Kateřina Bišová
Keyword(s):  
Cell Cycle ◽  
Chlamydomonas Reinhardtii ◽  
Cell Cycle Progression ◽  
Model Organism ◽  
Cycle Progression ◽  
Synchronous Cultures ◽  
Multiple Fission ◽  
First Choice ◽  
High Doses

Extensive in vivo replacement of hydrogen by deuterium, a stable isotope of hydrogen, induces a distinct stress response, reduces cell growth and impairs cell division in various organisms. Microalgae, including Chlamydomonas reinhardtii, a well-established model organism in cell cycle studies, are no exception. Chlamydomonas reinhardtii, a green unicellular alga of the Chlorophyceae class, divides by multiple fission, grows autotrophically and can be synchronized by alternating light/dark regimes; this makes it a model of first choice to discriminate the effect of deuterium on growth and/or division. Here, we investigate the effects of high doses of deuterium on cell cycle progression in C. reinhardtii. Synchronous cultures of C. reinhardtii were cultivated in growth medium containing 70 or 90% D2O. We characterize specific deuterium-induced shifts in attainment of commitment points during growth and/or division of C. reinhardtii, contradicting the role of the “sizer” in regulating the cell cycle. Consequently, impaired cell cycle progression in deuterated cultures causes (over)accumulation of starch and lipids, suggesting a promising potential for microalgae to produce deuterated organic compounds.

scholarly journals Lineage-specific SoxR-mediated Regulation of an Endoribonuclease Protects Non-enteric Bacteria from Redox-active Compounds

2016 ◽  
Vol 292 (1) ◽  
pp. 121-133 ◽  
Author(s):  
Jisun Kim ◽  
Chulwoo Park ◽  
James A. Imlay ◽  
Woojun Park
Keyword(s):  
Enteric Bacteria ◽  
Active Compounds ◽  
Redox Active

Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders

1998 ◽  
Vol 4 (2) ◽  
pp. 63-69 ◽  
Author(s):  
O A Khan ◽  
H Jiang ◽  
P S Subramaniam ◽  
H M Johnson ◽  
S S Dhib-Jalbut
Keyword(s):  
Therapeutic Option ◽  
High Dose ◽  
Interferon Tau ◽  
Unique Type ◽  
Immune Mediated ◽  
High Concentrations ◽  
Ifn Treatment ◽  
High Doses ◽  
Mulitple Sclerosis

The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type 1 recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type 1 IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFNt is a unique type 1 interferon discovered for its role in the animal reproductive cycle. It differs from other type 1 IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFNt has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFNt on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFNt on human cells at high concentrations as well as immunomodulating properties consistent with other type 1 IFNs including an antilymphoproliferative effect and inhibition of IFNg-induced HLA class II expression. These results suggest that OvIFNt could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.

scholarly journals Vitamin B12 transport in blood. I. Congenital deficiency of transcobalamin II

Blood ◽  
1975 ◽  
Vol 45 (1) ◽  
pp. 71-82 ◽  
Author(s):  
E Gimpert ◽  
M Jakob ◽  
WH Hitzig
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Congenital Deficiency ◽  
Complete Clinical Remission ◽  
High Concentrations ◽  
High Doses ◽  
Vitamin B12 Binder ◽  
Very High ◽  
Transcobalamin Ii

Abstract Some characteristics of vitamin B12 binding and transport in the serum of an infant with congenital hereditary transcobalamin II (TC II) deficiency were studied using the following parameters and methods: vitamin B12 level and binding capacity; electrophoretic mobility in polyacrylamide gel electrophoresis; various immunodiffusion and absorption experiments, using a specific anti-TC II antiserum and the patient's serum as antigen. The results of these studies point to a deficient synthesis of TC II. Parenteral administration of high doses of vitamin B12 was followed by rapid and complete clinical remission and the appearance of vitamin B12 binder in the alpha 2 region which is similar to “fetal binder.” Thus, very high concentrations of vitamin B12, either carrier free or bound to this alpha 2 binder, were able to correct the disturbed physiology of TC II deficiency, presumably by normalization of DNA-thymine synthesis.

scholarly journals High Doses of Halotolerant Gut-IndigenousLactobacillus plantarumReduce Cultivable Lactobacilli in Newborn Calves without Increasing Its Species Abundance

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Alexander Rodriguez-Palacios ◽  
Henry R. Staempfli ◽  
J. Scott Weese
Keyword(s):  
Inhibitory Activity ◽  
Body Weight Gain ◽  
Species Abundance ◽  
Ecological Effect ◽  
Double Blind ◽  
Reduced Body ◽  
Newborn Calves ◽  
High Concentrations ◽  
High Doses

To elucidate the ecological effect of high oral doses of halotolerant (resistant to table salt) indigenous-gut bacteria on other commensals early in life, we conducted a culture-based study to quantify the effect of intestinalLactobacillus plantarumstrain of bovine origin (with remarkable aerobic growth capabilities and inhibitory activity againstEscherichia coliO157:H7 and F5) on clinical health and gut lactobacilli/coliforms in newborn calves. In a double-blind placebo-randomized trial twelve colostrum-fed calves, consecutively born at a farm, were fedL. plantarumwithin 12 hours from birth at low (107-8 CFU/day) or high concentrations (1010-11) or placebo (q24 h, 5 d; 10 d follow-up). We developed a 2.5% NaCl-selective culture strategy to facilitate the enumeration ofL. plantarum-strain-B80, and tested 384 samples (>1,152 cultures).L. plantarum-B80-like colonies were detected in a large proportion of calves (58%) even before their first 24 hours of life indicating endemic presence of the strain in the farm. In contrast to studies where human-derivedLactobacillusLGG orrhamnosushad notoriously high, but short-lived, colonization, we found thatL. plantarumcolonized stably with fecal shedding of6±1 log10·g−1(irrespective of dose,P>0.2). High doses significantly reduced other fecal lactic acid bacteria (e.g., lactobacilli,P<0.01) and slightly reduced body weight gain in calves after treatment. For the first time, a halotolerant strain ofL. plantarumwith inhibitory activity against a human pathogen has the ability to inhibit other lactobacilliin vivowithout changing its species abundance, causing transintestinal translocation, or inducing clinical disease. The future selection of probiotics based on halotolerance may expand therapeutic product applicability.

scholarly journals High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn- IgG complexes

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 184-193 ◽  
Author(s):  
HU Lutz ◽  
P Stammler ◽  
E Jelezarova ◽  
M Nater ◽  
PJ Spath
Keyword(s):  
Inflammatory Diseases ◽  
Factor H ◽  
Human Igg ◽  
Partial Protection ◽  
Beneficial Effects ◽  
High Concentrations ◽  
High Doses ◽  
Immune Aggregates

Abstract Intravenously applied human IgG has beneficial effects in treating inflammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activation and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates. IgG added at 2 to 10 mg/mL stimulated the physiologic inactivation of C3b-containing complexes twofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-containing complexes. Exogenous IgG (5 mg/mL) also stimulated inactivation of purified C3b2-IgG complexes, whereby their half-life dropped from 3–4 to 1.5 minutes in 20% serum. IgG appeared to act like a modulator of factor H and I because it did not stimulate inactivation of C3b-containing complexes in factor I-deficient serum. Thus, the known partial protection of C3bn-IgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG. The ability of high doses of IgG to stimulate complement inactivation is a novel regulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations.

scholarly journals The Real-Time-Based Assessment of the Microbial Killing by the Antimicrobial Compounds of Neutrophils

2011 ◽  
Vol 11 ◽  
pp. 2382-2390 ◽  
Author(s):  
J. T. Atosuo ◽  
E.-M. Lilius
Keyword(s):  
Real Time ◽  
Antimicrobial Agents ◽  
Hypochlorous Acid ◽  
Bacterial Cells ◽  
Photorhabdus Luminescens ◽  
Bacterial Luciferase ◽  
E Coli ◽  
High Concentrations ◽  
Time Basis ◽  
K 12

A recombinantEscherichia coliK-12 strain, transformed with a modified bacterial luciferase gene (luxABCDE) fromPhotorhabdus luminescens, was constructed in order to monitor the activity of various antimicrobial agents on a real-time basis. ThisE. coli-lux emitted, without any addition of substrate, constitutive bioluminescence (BL), which correlated to the number of viable bacterial cells. The decrease in BL signal correlated to the number of killed bacterial cells. Antimicrobial activity of hydrogen peroxide (H2O2) and myeloperoxidase (MPO) was assessed. In high concentrations, H2O2alone had a bacteriocidic function and MPO enhanced this killing by forming hypochlorous acid (HOCl). Taurine, the known HOCl scavenger, blocked the killing by MPO. WhenE. coli-lux was incubated with neutrophils, similar killing kinetics was recorded as in H2O2/MPO experiments. The opsonization of bacteria enhanced the killing, and the maximum rate of the MPO release from lysosomes coincided with the onset of the killing.

scholarly journals Biphasic Dose–Response Induced by PCB150 and PCB180 in HeLa Cells and Potential Molecular Mechanisms

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582091004
Author(s):  
Ainy Zehra ◽  
Muhammad Zaffar Hashmi ◽  
Abdul Majid Khan ◽  
Tariq Malik ◽  
Zaigham Abbas
Keyword(s):  
Hela Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Genotoxic Effects ◽  
Species Formation ◽  
Low Concentrations ◽  
Extracellular Signal ◽  
High Concentrations ◽  
High Doses ◽  
Dose Dependent

The polychlorinated biphenyls (PCBs) are persistent and their dose-dependent toxicities studies are not well-established. In this study, cytotoxic and genotoxic effects of PCB150 and PCB180 in HeLa cells were studied. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the cell proliferation was stimulated at low doses (10−3 and 10−2 µg/mL for 12, 24, 48, and 72 hours) and inhibited at high doses (10 and 15 µg/mL for 24, 48, and 72 hours) for both PCBs. Increase in reactive oxygen species formation was observed in the HeLa cells in a time- and dose-dependent manner. Malondialdehyde and superoxide dismutase showed increased levels at high concentrations of PCBs over the time. Glutathione peroxidase expression was downregulated after PCBs exposure, suggested that both PCB congeners may attributable to cytotoxicity. Comet assay elicited a significant increase in genotoxicity at high concentrations of PCBs as compared to low concentrations indicating genotoxic effects. PCB150 and PCB180 showed decrease in the activity of extracellular signal–regulated kinase 1/2 and c-Jun N-terminal kinase at high concentrations after 12 and 48 hours. These findings may contribute to understanding the mechanism of PCBs-induced toxicity, thereby improving the risk assessment of toxic compounds in humans.

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