A comparative analysis of the cell biology of senescence and aging

Various intracellular organelles, such as lysosomes, mitochondria, nuclei, and cytoskeletons, change during replicative senescence, but the utility of these changes as general markers of senescence and their significance with respect to functional alterations have not been comprehensively reviewed. Furthermore, the relevance of these alterations to cellular and functional changes in aging animals is poorly understood. In this paper, we review the studies that report these senescence-associated changes in various aging cells and their underlying mechanisms. Changes associated with lysosomes and mitochondria are found not only in cells undergoing replicative or induced senescence but also in postmitotic cells isolated from aged organisms. In contrast, other changes occur mainly in cells undergoing in vitro senescence. Comparison of age-related changes and their underlying mechanisms in in vitro senescent cells and aged postmitotic cells would reveal the relevance of replicative senescence to the physiological processes occurring in postmitotic cells as individuals age.     

The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis

Presenilin-1 (PS1) gene encodes the catalytic component of γ-secretase, which proteolytically processes several type I transmembrane proteins. We here present evidence that the cytosolic peptide efnB2/CTF2 produced by the PS1/γ-secretase cleavage of efnB2 ligand promotes EphB4 receptor-dependent angiogenesis in vitro. EfnB2/CTF2 increases endothelial cell sprouting and tube formation, stimulates the formation of angiogenic complexes that include VE-cadherin, Raf-1 and Rok-α, and increases MLC2 phosphorylation. These functions are mediated by the PDZ-binding domain of efnB2. Acute downregulation of PS1 or inhibition of γ-secretase inhibits the angiogenic functions of EphB4 while absence of PS1 decreases the VE-cadherin angiogenic complexes of mouse brain. Our data reveal a mechanism by which PS1/γ-secretase regulates efnB2/EphB4 mediated angiogenesis.     

Calmodulin interacts with MLO protein to regulate defence against mildew in barley

In plants, defence against specific isolates of a pathogen can be triggered by the presence of a corresponding race-specific resistance gene, whereas resistance of a more broad-spectrum nature can result from recessive, presumably loss-of-regulatory-function, mutations. An example of the latter are mlo mutations in barley, which have been successful in agriculture for the control of powdery mildew fungus (Blumeria graminis f. sp. hordei; Bgh). MLO protein resides in the plasma membrane, has seven transmembrane domains, and is the prototype of a sequence-diversified family unique to plants, reminiscent of the seven-transmembrane receptors in fungi and animals. In animals, these are known as G-protein-coupled receptors and exist in three main families, lacking sequence similarity, that are thought to be an example of molecular convergence. MLO seems to function independently of heterotrimeric G proteins. We have identified a domain in MLO that mediates a Ca2+-dependent interaction with calmodulin in vitro. Loss of calmodulin binding halves the ability of MLO to negatively regulate defence against powdery mildew in vivo. We propose a sensor role for MLO in the modulation of defence reactions.     

An area for vergence eye movement in primate frontal cortex

To view objects at different distances, humans rely on vergence eye movements to appropriately converge or diverge the eyes and on ocular accommodation to focus the object. Despite the importance of these coordinated eye movements (the 'near response') very little is known about the role of the cerebral cortex in their control. As near-response neurons exist within the nucleus reticularis tegmenti pontis, which receives input from the frontal eye field region of frontal cortex, and this cortical region is known to be involved in saccadic and smooth-pursuit eye movements, we propose that a nearby region might play a role in vergence and ocular accommodation. Here we provide evidence from rhesus monkeys that a region of frontal cortex located immediately anterior to the saccade-related frontal eye field region is involved in vergence and ocular accommodation, and in the sensorimotor transformations required for these eye movements. We conclude that the macaque frontal cortex is involved in the control of all voluntary eye movements, and suggest that the definition of the frontal eye fields should be expanded to include this region.     

A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.     

Development of a propulsion system for a biomimetic thruster

We studied theoretically and experimentally a biomimetic propulsion system inspired by the motility mechanisms of bacteria such as E. coli. Our goal was to investigate the effect of the ??complex?? filament of Rhizobium Meliloti bacteria on thrust force. The complex filament is a helically perturbed filament, similar to a plain filament threaded through a small helix. The propulsive performance of this system was estimated by modeling the dynamics of helical wave motion in viscous fluid. The model consists of a helical filament which is axially rotated at angular velocity ??. Resistive force theory (RFT) was applied to this model to calculate the thrust force and required torque. The Buckingham PI theorem (non-dimensional analysis) was also used to analyze the theoretical results. The procedure for making a complex filament with various pitch angles ?? _s from a small helix and plain filament is explained in detail. To validate the theoretical results for helical wave propulsion and compare the characteristics of complex and plain filaments together, an experiment was performed to measure the thrust forces in silicone oil. The experimental results agreed with the theoretical values predicted by RFT. The thrust forces of complex filaments depended on the shape of small helix winding. The maximum thrust force was achieved at a small helix pitch angle of ?? _s = 45°. In addition, we found that the thrust force generated by a complex filament had a value about 10% higher than that of a plain filament with the same equivalent diameter d _e .