Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci

Leaf senescence is the terminal stage in the development of perennial plants. Massive physiological changes occur that lead to the shut down of photosynthesis and a cessation of growth. Leaf senescence involves the selective destruction of the chloroplast as the site of photosynthesis. Here, we show that 13-lipoxygenase (13-LOX) accomplishes a key role in the destruction of chloroplasts in senescing plants and propose a critical role of its NH2-terminal chloroplast transit peptide. The 13-LOX enzyme identified here accumulated in the plastid envelope and catalyzed the dioxygenation of unsaturated membrane fatty acids, leading to a selective destruction of the chloroplast and the release of stromal constituents. Because 13-LOX pathway products comprise compounds involved in insect deterrence and pathogen defense (volatile aldehydes and oxylipins), a mechanism of unmolested nitrogen and carbon relocation is suggested that occurs from leaves to seeds and roots during fall.

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Effects of acute exercise on the gluconeogenic capacity of periportal and perivenous hepatocytes

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.3.1099 ◽

2001 ◽

Vol 91 (3) ◽

pp. 1099-1104 ◽

Cited By ~ 3

Author(s):

François Désy ◽

Yan Burelle ◽

Patrice Bélanger ◽

Marielle Gascon-Barré ◽

Jean-Marc Lavoie

Keyword(s):

Incubation Medium ◽

Acute Exercise ◽

Metabolic Response ◽

Liver Perfusion ◽

Glucose Production ◽

Selective Destruction ◽

Single Bout ◽

Lactate And Pyruvate ◽

The Difference ◽

Exercise Induced

The present study was conducted to examine the effect of a single bout of exercise (rodent treadmill, 60 min at 26 m/min, 0% grade) on the gluconeogenic activity of periportal hepatocytes (PP-H) and perivenous hepatocytes (PV-H) in fasted (18 h) rats. Isolated PP-H and PV-H, obtained by selective destruction following liver perfusion with digitonin and collagenase, were incubated with saturating concentrations of alanine (Ala; 20 mM) or a mixture of lactate and pyruvate (Lac+Pyr; 20:2 mM) to determine the glucose production flux ( J glucose) in the incubation medium. Results show that, in the resting conditions, J glucose from all exogenous substrates was significantly higher ( P < 0.01) in PP-H than in PV-H. Exercise, compared with rest, resulted in a higher J glucose ( P < 0.01) from Lac+Pyr substrate in the PV-H but not in the PP-H, resulting in the disappearance of the difference in J glucosebetween PP-H and PV-H. Exercise, compared with rest, led to a higher J glucose ( P < 0.01) from Ala substrate in both PP-H and PV-H. However, the exercise-induced increase in J glucose (gluconeogenic activity) from Ala substrate was higher in PV-H than in PP-H, resulting, as from Lac+Pyr substrate, in the disappearance ( P > 0.05) of the difference of J glucose between PP-H and PV-H. It is concluded that exercise differentially stimulates the gluconeogenic activity of PV-H to a larger extent than PP-H, indicative of a heterogenous metabolic response of hepatocytes to exercise.

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The effect of destruction of the bundle of His or the atrioventricular node on cyclopropane–adrenaline cardiac arrhythmias

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y70-038 ◽

1970 ◽

Vol 48 (4) ◽

pp. 207-215 ◽

Cited By ~ 1

Author(s):

Betty I. Sasyniuk ◽

Peter E. Dresel

Keyword(s):

Coronary Artery ◽

Cardiac Arrhythmias ◽

Atrioventricular Node ◽

Circumflex Coronary Artery ◽

Selective Destruction ◽

Anesthetized Dogs ◽

Bundle Of His

Destruction of the bundle of His abolished bigeminal rhythms produced by adrenaline in thiopentone–cyclopropane anesthetized dogs. Bigeminal rhythms were still elicited, however, after selective destruction of the A–V node. Destruction of the bundle of His did not prevent multifocal arrhythmias but did increase the dose of adrenaline required to induce them. Multifocal arrhythmias produced after destruction of the bundle of His were abolished by injections of acetylcholine into the left anterior descending, but not the circumflex coronary artery, results opposite to those obtained in normal hearts.

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Genetically-Engineered Protease-Activated Triggers in a Pore-Forming Protein

MRS Proceedings ◽

10.1557/proc-330-209 ◽

1993 ◽

Vol 330 ◽

Cited By ~ 1

Author(s):

Barbara Walker ◽

Nathan Walsh ◽

Hagan Bayley

Keyword(s):

Genetic Engineering ◽

Cancer Cells ◽

Pore Formation ◽

Polypeptide Chain ◽

Genetically Engineered ◽

Recognition Sequence ◽

Selective Activation ◽

Selective Destruction ◽

Pore Forming Proteins ◽

Central Loop

ABSTRACTProtease-activated triggers have been introduced Into a pore-forming protein, staphylococcal a-hemolysin (αHL). The hemolysin was remodeled by genetic engineering to form two-chain constructs with redundant polypeptide sequences at the central loop, the Integrity of which Is crucial for efficient pore formation. The new hemolysins are activated when the polypeptide extensions are removed by proteases. By alterating the protease recognition sequence in the loop, selective activation by specified proteases can be obtained. Protease-triggered pore-forming proteins might be used for the selective destruction of cancer cells that bear tumor-associated proteases. When certain two-chain constructs are treated with proteases, a full-length polypeptide chain forms as the result of a protease-mediated transpeptidation reaction. This reaction might be used to produce chimeric hemolysins that are Inaccessible by conventional routes.

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