scholarly journals Half-Life Systematics across theN=126Shell Closure: Role of First-Forbidden Transitions in theβDecay of Heavy Neutron-Rich Nuclei

2014 ◽  
Vol 113 (2) ◽  
Author(s):  
A. I. Morales ◽  
J. Benlliure ◽  
T. Kurtukián-Nieto ◽  
K.-H Schmidt ◽  
S. Verma ◽  
...  
Keyword(s):  
Half Life ◽  
Forbidden Transitions

Prophylaxis for Hemophilia in the Era of Extended Half-Life Factor VIII/Factor IX Products

2016 ◽  
Vol 42 (05) ◽  
pp. 518-525 ◽  
Author(s):  
Erik Berntorp ◽  
Nadine Andersson
Keyword(s):  
Half Life ◽  
Safety Margin ◽  
Clinical Development ◽  
Factor Ix ◽  
Life Extension ◽  
Bleeding Events ◽  
Treatment And Prevention ◽  
Trough Levels ◽  
Life Factor

There are two main bioengineering approaches to extending the half-life of factor (F)VIII or FIX products used for hemophilia replacement therapy. These are fusion to Fc-immunoglobulin G (FVIII and FIX) or to albumin (FIX) or pegylation/glycopegylation (FVIII and FIX). Four FVIII and three FIX products are in clinical development or have recently been licensed in regions of the world. The reported half-life extension is approximately 1.5-fold for FVIII and 2.5-fold, or even longer, for FIX. Clinical trials have shown promising results with respect to extension of dose intervals and efficacy in the treatment and prevention of bleeding events. The role of these products in clinical practice has been discussed in terms of either improving convenience and adherence through prolongation of the interval between infusions or maintaining current intervals thereby increasing trough levels and the safety margin against bleeds. This review of extended half-life products addresses the possibilities and problems of their introduction in hemophilia treatment.

scholarly journals Evaluation of antibiotics as a methodological procedure to inhibit free-living and biofilm bacteria in marine zooplankton culture

2016 ◽  
Vol 88 (suppl 1) ◽  
pp. 733-746 ◽  
Author(s):  
Vanessa O. Agostini ◽  
Alexandre J. Macedo ◽  
Erik Muxagata
Keyword(s):  
Half Life ◽  
Culture Medium ◽  
Metabolic Inhibitors ◽  
Penicillin G ◽  
Streptomycin Sulphate ◽  
Free Living ◽  
Marine Zooplankton ◽  
Scientific Experiments ◽  
Biofilm Bacteria

There is a problem with keeping culture medium completely or partially free from bacteria. The use of prokaryotic metabolic inhibitors, such as antibiotics, is suggested as an alternative solution, although such substances should not harm non-target organisms. Thus, the aim of this study was to assess the effectiveness of antibiotic treatments in inhibiting free-living and biofilm bacteria and their half-life in artificial marine environment using the copepod Acartia tonsa as bioindicador of non-harmful antibiotic combinations. Regarding to results, the application of 0.025 g L-1 penicillin G potassium + 0.08 g L-1 streptomycin sulphate + 0.04 g L-1 neomycin sulphate showed great potential for use in marine cultures and scientific experiments without lethal effects to non-target organisms. The effect of this combination starts within the first six hours of exposure and reduces up to 93 % the bacterial density, but the half-life is short, requiring replacement. No adverse changes in water quality were observed within 168 hours of exposure. As a conclusion, we can infer that this treatment was an effective procedure for zooplankton cultures and scientific experiments with the aim of measuring the role of free-living and biofilm in the marine community.

scholarly journals FOXO3a is stabilized by USP18-mediated de-ISGylation and inhibits TGF-β1-induced fibronectin expression

2019 ◽  
Vol 68 (3) ◽  
pp. 786-791 ◽  
Author(s):  
Ban Wang ◽  
Yanhui Li ◽  
Heather Wang ◽  
Jing Zhao ◽  
Yutong Zhao ◽  
...  
Keyword(s):  
Half Life ◽  
Transforming Growth Factor ◽  
Fibroblast Cells ◽  
Post Translational Modification ◽  
Human Lung Fibroblast ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Fibronectin Expression ◽  
Tgf Β1

FOXO3a belongs to a family of transcription factors characterized by a conserved forkhead box DNA-binding domain. It has been known to regulate various cellular processes including cell proliferation, apoptosis and differentiation. Post-translational modifications of FOXO3a and their roles in the regulation of FOXO3a activity have been well-documented. FOXO3a can be phosphorylated, acetylated and ubiquitinated, however, the ISGylation of FOXO3a has not been reported. Protein overexpression, ISGylation and half-life were measured to determine the post-translational modification of FOXO3a. Human fibroblast cells were treated with transforming growth factor (TGF)-β1 to determine the role of FOXO3a ISGylation in TGF-β1 signaling. FOXO3a’s half-life is around 3.7 hours. Inhibition of the proteasome, not lysosome, extends its half-life. ISGylation, but not ubiquitination of FOXO3a, is increased in the presence of the proteasome inhibitor. Overexpression of ISG15 increases FOXO3a degradation, while overexpression of USP18 stabilizes FOXO3a through de-ISGylation. These results suggest that FOXO3a is degraded in the ISGylation and proteasome system, which can be reversed by USP18, an ISG15-specific deubiquitinase. This study reveals a new molecular mechanism by which ISGylation regulates FOXO3a degradation. Furthermore, we show that the overexpression of FOXO3a attenuated TGF-β1-induced fibronectin expression in human lung fibroblast cells without altering Smad2/3 expression and activation. FOXO3a can be ISGylated, which can regulate FOXO3a stability. USP18/FOXO3a pathway is a potential target for treating TGF-β1-mediated fibrotic diseases such as idiopathic pulmonary fibrosis.

Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation

Science ◽  
2018 ◽  
Vol 361 (6403) ◽  
pp. 701-704 ◽  
Author(s):  
Jaechul Lim ◽  
Dongwan Kim ◽  
Young-suk Lee ◽  
Minju Ha ◽  
Mihye Lee ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Half Life ◽  
Messenger Rna ◽  
Mrna Translation ◽  
Posttranscriptional Gene Regulation ◽  
And Function ◽  
Mrna Half Life ◽  
In Cells

RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3′ end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.

scholarly journals Sorption and Degradation Potential of Pharmaceuticals in Sediments from a Stormwater Retention Pond

Water ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 526 ◽  
Author(s):  
Fan Liu ◽  
Asbjørn Nielsen ◽  
Jes Vollertsen
Keyword(s):  
Half Life ◽  
Pond Water ◽  
Organic Micropollutants ◽  
Partitioning Coefficient ◽  
Retention Pond ◽  
Retention Ponds ◽  
Water Partitioning ◽  
Stormwater Retention ◽  
Sorption Potential

Stormwater retention ponds commonly receive some wastewater through misconnections, sewer leaks, and sewer overloads, all of which leads to unintended loads of organic micropollutants, including pharmaceuticals. This study explores the role of pond sediment in removing pharmaceuticals (naproxen, carbamazepine, sulfamethoxazole, furosemide, and fenofibrate). It quantifies their sorption potential to the sediments and how it depends on pH. Then it addresses the degradability of the pharmaceuticals in microcosms holding sediment beds and pond water. The sediment-water partitioning coefficient of fenofibrate varied little with pH and was the highest (average log Kd: 4.42 L kg−1). Sulfamethoxazole had the lowest (average log Kd: 0.80 L kg−1), varying unsystematically with pH. The coefficients of naproxen, furosemide and carbamazepine were in between. The degradation by the sediments was most pronounced for sulfamethoxazole, followed by naproxen, fenofibrate, furosemide, and carbamazepine. The first three were all removed from the water phase with half-life of 2–8 days. Over the 38 days the experiment lasted, they were all degraded to near completion. The latter two were more resistant, with half-lives between 1 and 2 months. Overall, the study indicated that stormwater retention ponds have the potential to remove some but not all pharmaceuticals contained in wastewater contributions.

Role of enhanced half-life factor VIII and IX in the treatment of haemophilia

2015 ◽  
Vol 169 (6) ◽  
pp. 768-776 ◽  
Author(s):  
Ali J. Mahdi ◽  
Samya G. Obaji ◽  
Peter W. Collins
Keyword(s):  
Factor Viii ◽  
Half Life ◽  
Viii And Ix ◽  
Life Factor

ALTERED INTERACTION OF THROMBIN AND ANTITHROMBIN III WITH THE VASCULAR WALL

1987 ◽  
Author(s):  
G Bashkov ◽  
T Kalishevekaya ◽  
S Strukova
Keyword(s):  
Nephrotic Syndrome ◽  
Half Life ◽  
Antithrombin Iii ◽  
Fold Increase ◽  
Vascular Wall ◽  
Blood Stream ◽  
Soluble Fibrin ◽  
Heymann Nephritis ◽  
Plasma Half Life

The role of the endothelial injury in the development of the thrombophylic state was studied in rats with nephrotic syndrome (NS,Heymann nephritis).There were a 6-fold increase of the soluble fibrin concentration and a 30% decrease of plasma antithrombin III (AT) activity in the NSIt was found that the plasma half-life of 125 J-labelled α-thrombin (10-7 M) is 3,0 ± 0,6 min in control animals and 4,0 ± 0,1 min in NS rats. At 20 min following the administration of bovine 125J-thrombin it was observed that in normal animals 84% of the radiolabelled enzyme was bound with vessel wall.while in NS rats the figure was only 63% (p< 0,05). The alteration of thrombin binding to the vascular wall lead to an increase in the amount of soluble fibrin-monomer and AT-proteinase complexes.AT-thrombin complexes and a proteolytically modified form of AT (Mr<68 kDa) were isolated from NS rats plasma by affinity chromatography on heparin-sepharose and chromatofocusing.At 3 min following injection of a 100-fold molar excess of bovine AT (1,7 .10-5 M) it was observed that 35% of thrombin reversibly bound to the endothelium could be detected in the circulation of normal rats. The same excess of AT induced only a 10% (p<0,001) release of 125J-thrombin to the blood stream in the NS rats through the formation of 125 J-thrombin complexes with Mr≥100 kDa.It is being proposed that injury of the vascular wall in the NS animals facilitated the interaction of the enzyme with the substrate (fibrinogen) and inhibitor (AT), and leads to ineffective inactivation of thrombin bound to the endothelium by AT.

scholarly journals Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: Possible role of the prolonged half-life of the immunogen

Vaccine ◽  
2009 ◽  
Vol 27 (6) ◽  
pp. 857-863 ◽  
Author(s):  
Mei-Yun Zhang ◽  
Yanping Wang ◽  
Marie K. Mankowski ◽  
Roger G. Ptak ◽  
Dimiter S. Dimitrov
Keyword(s):  
Half Life ◽  
Neutralizing Activity ◽  
Serum Igg ◽  
Hiv 1

scholarly journals Role of the Fc Region in the Vitreous Half-Life of Anti-VEGF Drugs

2017 ◽  
Vol 58 (10) ◽  
pp. 4261 ◽  
Author(s):  
Kwangsic Joo ◽  
Sang Jun Park ◽  
Yewon Choi ◽  
Jung Eun Lee ◽  
Young Mi Na ◽  
...  
Keyword(s):  
Half Life ◽  
Anti Vegf

scholarly journals Role of LAMP-2 in Lysosome Biogenesis and Autophagy

2002 ◽  
Vol 13 (9) ◽  
pp. 3355-3368 ◽  
Author(s):  
Eeva-Liisa Eskelinen ◽  
Anna Lena Illert ◽  
Yoshitaka Tanaka ◽  
Günter Schwarzmann ◽  
Judith Blanz ◽  
...  
Keyword(s):  
Half Life ◽  
Lysosomal Enzymes ◽  
State Level ◽  
Autophagic Vacuoles ◽  
Lysosome Biogenesis ◽  
Golgi Region ◽  
Activity Measurements ◽  
Phenotype Analysis ◽  
Mannose 6 Phosphate

In LAMP-2–deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart. Here we extend the phenotype analysis using cultured hepatocytes. In LAMP-2–deficient hepatocytes the half-life of both early and late autophagic vacuoles was prolonged as evaluated by quantitative electron microscopy. However, an endocytic tracer reached the autophagic vacuoles, indicating delivery of endo/lysosomal constituents to autophagic vacuoles. Enzyme activity measurements showed that the trafficking of some lysosomal enzymes to lysosomes was impaired. Immunoprecipitation of metabolically labeled cathepsin D indicated reduced intracellular retention and processing in the knockout cells. The steady-state level of 300-kDa mannose 6-phosphate receptor was slightly lower in LAMP-2–deficient hepatocytes, whereas that of 46-kDa mannose 6-phosphate receptor was decreased to 30% of controls due to a shorter half-life. Less receptor was found in the Golgi region and in vesicles and tubules surrounding multivesicular endosomes, suggesting impaired recycling from endosomes to the Golgi. More receptor was found in autophagic vacuoles, which may explain its shorter half-life. Our data indicate that in hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a subset of lysosomal enzymes. Autophagic vacuoles may accumulate due to impaired capacity for lysosomal degradation.

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