Repressing a Repressor: Gibberellin-Induced Rapid Reduction of the RGA Protein in Arabidopsis

2001 ◽  
Vol 13 (7) ◽  
pp. 1555-1566 ◽  
Author(s):  
A. L. Silverstone
Keyword(s):  
Author(s):  
William P. Wergin ◽  
P. F. Bell ◽  
Rufus L. Chaney

In dicotyledons, Fe3+ must be reduced to Fe2+ before uptake and transport of this essential macronutrient can occur. Ambler et al demonstrated that reduction along the root could be observed by the formation of a stain, Prussian blue (PB), Fe4 [Fe(CN)6]3 n H2O (where n = 14-16). This stain, which is an insoluble precipitate, forms at the reduction site when the nutrient solution contains Fe3+ and ferricyanide. In 1972, Chaney et al proposed a model which suggested that the Fe3+ reduction site occurred outside the cell membrane; however, no physical evidence to support the model was presented at that time. A more recent study using the PB stain indicates that rapid reduction of Fe3+ occurs in a region of the root containing young root hairs. Furthermore the most pronounced activity occurs in plants that are deficient in Fe. To more precisely localize the site of Fe3+ reduction, scanning electron microscopy (SEM), x-ray analysis, and transmission electron microscopy (TEM) were utilized to examine the distribution of the PB precipitate that was induced to form in roots.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S213-S213
Author(s):  
Karen J Shaw ◽  
Charles D Giamberardino ◽  
Quinlyn A Soltow ◽  
Jennifer Tenor ◽  
Dena Toffaletti ◽  
...  

Abstract Background Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. New oral treatment options are needed that demonstrate rapid reductions in CFU in CSF and brain tissue. APX2039 is a novel inhibitor of the fungal Gwt1 enzyme, which catalyzes an early step in glycosylphosphatidyl inositol (GPI) anchor biosynthesis. It is highly active against both C. neoformans and C. gattii and has previously demonstrated significant efficacy in a mouse delayed-treatment model of CM. CSF Fungal Burden in Rabbits Methods Male New Zealand White rabbits were inoculated with C. neoformans H99 (1.4 ×106 CFU) directly into the cisterna magna. Rabbits were immunosuppressed with cortisone acetate at 7.5 mg/kg (i.m.), starting on Day -1 relative to inoculation and then administered drug daily throughout the 14-day experimental period. Treatment was initiated on Day 2 postinfection and continued through Day 14 consisting of: 50 mg/kg APX2039 PO (BID), 80 mg/kg fluconazole (FLU) PO (QD), c) 1 mg/kg amphotericin B deoxycholate (AMB) IV (QD); and vehicle control. CSF was removed via an intracisternal tap on Days 2, 7, 10 and 14 post-infection and CFU/ml was assessed. Animals were sacrificed on Day 14 and CFU/g brain tissue was assessed. Results APX2039 demonstrated rapid reduction in CFU in both CSF and brain tissue. The range in CFU values in rabbit CSF is shown (Figure). Reductions in CFU were statistically different from the control group for all treatment groups. APX2039 was also different from both FLU and AMB and resulted in sterilization in CSF by Day 10. Brain harvested on Day 14 demonstrated a reduction in CFU/g tissue vs control of 1.8 log10 and 3.4 log10 for FLU and AMB, respectively, while a > 6 log10 reduction (tissue sterilization) was observed for APX2039. Conclusion APX2039 demonstrated potent efficacy in a rabbit model of CM. The more rapid clearance in CSF than either AMB or FLU, as well as > 6 log10 reduction in brain CFU highlights the unique properties of this drug, warranting further investigation of this molecule for the treatment of CM. Disclosures Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Charles D. Giamberardino, Jr., MR, Box (Shareholder) John R. Perfect, MD, amplyx (Grant/Research Support)astellas (Grant/Research Support)astellas (Grant/Research Support)


2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Marek Malecki ◽  
Bianka Saetre

Background: For many deadly viruses, there are no preventive and / or therapeutic vaccines approved by health authorities World-wide (e.g., HIV, Ebola, Dengue, and many others). Although, for some viruses, prophylactic vaccines are very effective (e.g., HBV, Polio, Rota, and many others). In this realm, we design, manufacture, test, and streamline into the clinics novel viral universal vaccines (VUV). VUV have such unique features, that medical vaccination or natural infection induced immunity against some viruses (e.g., HBV) in patients, who became infected with other viruses (e.g., HIV), upon the VUV’s administration, is redirected against these other, newly infecting viruses (e.g., HIV). Specific Aim: The specific aim of this work was biomolecular engineering of the HIV universal vaccine (HIVUV) comprising the two main functional domains: CD4 or anti-gp120 - as the HIV tagging domain and HBsAg - as the immune response eliciting domain, so that upon its administration the HBV medical immunization or natural infection induced immunity would be redirected, accelerated, and amplified to fight the HIV infection. Healthy Donors and Patients: Per the Institutional Review Board approval and in compliance with the Declaration of Helsinki, all healthy donors and patients were presented with the Patients’ Bill of Rights and provided Patient Informed Consent. All the procedures were pursued by the licensed medical doctors. Methods & Results: We have biomolecularly engineered HIV universal vaccine (HIVUV) comprising human CD4 or anti-gp120 and HBsAg of HBV. By immunoblotting and magnetic activated molecular sorting, we have demonstrated high specificity of this vaccine in binding HIV. By flow cytometry and nuclear magnetic resonance, we have demonstrated high efficacy of these vaccines to engage HBV immunized patients’ immune system to work against HIV. Administration of HIVUV to blood or lymph of the HIV+ patients resulted in rapid reduction of the HIV viremia down to undetectable. It also resulted in protection of populations of CD4+ cells against HIV caused decline. Conclusions: We have demonstrated the proof of concept for high efficacy of VUV, specifically HIVUV, in annihilating HIV. Nevertheless, the same compositions, processes, and methods, for persons skilled in biotechnology, pharmacogenomics, and molecular medicine, are adaptable for other deadly viral infections, which we vigorously pursue.


2020 ◽  
Vol 44 (17) ◽  
pp. 7218-7225 ◽  
Author(s):  
Haimei Xie ◽  
Duomou Ma ◽  
Wanyan Liu ◽  
Qian Chen ◽  
Yong Zhang ◽  
...  

The hydroxyl modified Zr-based MOFs is used for photocatalytic reduction of hexavalent chromium existing in wastewater.


1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.


2017 ◽  
Vol 8 ◽  
pp. 1649-1657 ◽  
Author(s):  
Antonín Brož ◽  
Lucie Bačáková ◽  
Pavla Štenclová ◽  
Alexander Kromka ◽  
Štěpán Potocký

Diamond nanoparticles, known as nanodiamonds (NDs), possess several medically significant properties. Having a tailorable and easily accessible surface gives them great potential for use in sensing and imaging applications and as a component of cell growth scaffolds. In this work we investigate in vitro interactions of human osteoblast-like SAOS-2 cells with four different groups of NDs, namely high-pressure high-temperature (HPHT) NDs (diameter 18–210 nm, oxygen-terminated), photoluminescent HPHT NDs (diameter 40 nm, oxygen-terminated), detonation NDs (diameter 5 nm, H-terminated), and the same detonation NDs further oxidized by annealing at 450 °C. The influence of the NDs on cell viability and cell count was measured by the mitochondrial metabolic activity test and by counting cells with stained nuclei. The interaction of NDs with cells was monitored by phase contrast live-cell imaging in real time. For both types of oxygen-terminated HPHT NDs, the cell viability and the cell number remained almost the same for concentrations up to 100 µg/mL within the whole range of ND diameters tested. The uptake of hydrogen-terminated detonation NDs caused the viability and the cell number to decrease by 80–85%. The oxidation of the NDs hindered the decrease, but on day 7, a further decrease was observed. While the O-terminated NDs showed mechanical obstruction of cells by agglomerates preventing cell adhesion, migration and division, the H-terminated detonation NDs exhibited rapid penetration into the cells from the beginning of the cultivation period, and also rapid cell congestion and a rapid reduction in viability. These findings are discussed with reference to relevant properties of NDs such as surface chemical bonds, zeta potential and nanoparticle types.


2020 ◽  
Vol 9 (1) ◽  
pp. 35
Author(s):  
Firoz Shah ◽  
Markus Gressler ◽  
Susan Nehzati ◽  
Michiel Op De Beeck ◽  
Luigi Gentile ◽  
...  

The ectomycorrhizal fungus Paxillus involutus decomposes proteins using a two-step mechanism, including oxidation and proteolysis. Oxidation involves the action of extracellular hydroxyl radicals (•OH) generated by the Fenton reaction. This reaction requires the presence of iron(II). Here, we monitored the speciation of extracellular iron and the secretion of iron(III)-reducing metabolites during the decomposition of proteins by P. involutus. X-ray absorption spectroscopy showed that extracellular iron was mainly present as solid iron(III) phosphates and oxides. Within 1 to 2 days, these compounds were reductively dissolved, and iron(II) complexes were formed, which remained in the medium throughout the incubation. HPLC and mass spectrometry detected five extracellular iron(III)-reducing metabolites. Four of them were also secreted when the fungus grew on a medium containing ammonium as the sole nitrogen source. NMR identified the unique iron(III)-reductant as the diarylcyclopentenone involutin. Involutin was produced from day 2, just before the elevated •OH production, preceding the oxidation of BSA. The other, not yet fully characterized iron(III)-reductants likely participate in the rapid reduction and dissolution of solid iron(III) complexes observed on day one. The production of these metabolites is induced by other environmental cues than for involutin, suggesting that they play a role beyond the Fenton chemistry associated with protein oxidation.


2015 ◽  
Vol 6 (2) ◽  
pp. 109-114 ◽  
Author(s):  
MN Hossain ◽  
M Rokanuzzaman ◽  
MA Rahman ◽  
M Bodiuzzaman ◽  
MA Miah

Over the past few decades deforestation has become the issue of global concern for its rapid reduction of biodiversity. The tropical moist deciduous Sal forest ecosystem of central Bangladesh is currently in a critical situation. Destructive anthropogenic and natural impacts coupled with overexploitation of forest resources have caused severe damage to the forest ecosystem. Due to rubber monoculture, expanding commercial fuel wood plantations & expanding agriculture, illegal cutting, encroachment of forest areas, and illegal poaching of wildlife, the Sal forest is losing biodiversity alarmingly. The study is based on intensive literature survey and tries to explore the overall deforestation situation and conservation practices for Madhupur Sal forest that comprises about 5% of the total forests in Bangladesh. The level of destruction of the natural Sal forest has pushed the forest-dwelling indigenous Garo community into cash crop production, forcing them to move away from their traditional subsistence economy. Now we need to address a joint conservation and improved management plan of the forest resources use. Thus all kinds of military establishments, construction of roads and highways for military purposes should be avoided and a policy of planned industrialization should be adopted to mitigate the adverse effect of industrialization. Findings of the study will help to identify the causes of deforestation and conservation of Madhupur Sal forest and also in other national parks in Bangladesh which ultimately conserve the biodiversity and help to maintain natural balance.DOI: http://dx.doi.org/10.3329/jesnr.v6i2.22105 J. Environ. Sci. & Natural Resources, 6(2): 109-114 2013


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