Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles.

Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between membranes and contribute to longevity in different manners. We previously found that a 2-fold up-regulation of Osh6, one of seven yeast oxysterol-binding proteins, remedies vacuolar morphology defects in mid-aged cells, partly down-regulates the target of rapamycin complex 1 (TORC1), and increases the replicative lifespan. At the molecular level, Osh6 transports phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) between the endoplasmic reticulum (ER) and the plasma membrane (PM).

Glutamate Transporters EAAT2 and EAAT5 Differentially Shape Synaptic Transmission from Rod Bipolar Cell Terminals.

Excitatory amino acid transporters (EAATs) control visual signal transmission in the retina by rapidly removing glutamate released from photoreceptors and bipolar cells (BCs). Although it has been reported that EAAT2 and EAAT5 are expressed at presynaptic terminals of photoreceptors and some BCs in mammals, the distinct functions of these two glutamate transporters in retinal synaptic transmission, especially at a single synapse, remain elusive. In this study, we found that EAAT2 was expressed in all BC types while coexisting with EAAT5 in rod bipolar (RB) cells and several types of cone BCs from mice of either sex.

OPTICAL COHERENCE TOMOGRAPHY PREDICTORS OF SHORT-TERM VISUAL ACUITY IN EYES WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION TREATED WITH INTRAVITREAL CONBERCEPT.

Purpose: To identify the spectral domain optical coherence tomography predictors of visual prognosis in retinal vein occlusion macular edema after intravitreal conbercept injection.

Methods: Retrospective cohort study of 63 treatment-naive retinal vein occlusion macular edema eyes received pro re nata intravitreal conbercept with at least 3 months of follow-up. The best-corrected visual acuity (BCVA) and optical coherence tomography scans were recorded at baseline, 1 month, and 3 months after starting therapy.

Madagascine Induces Vasodilatation via Activation of AMPK.

Madagascine (3-isopentenyloxyemodin) can be chemically synthesized or purified from several species, and it is found to have more potent biological activities than the parent compound emodin. The aim of this study is to characterize the vasodilatory effect of madagascine on vasoconstriction and sphingosylphosphorylcholine induced vasospasm in and reveal the potential mechanisms . The effects of madagascine on vasoconstriction of rat mesenteric resistance arteries (MRAs) induced by K, methoxamine, and endothelin-1 were, respectively, studied.

Stainless steel corrosion scale formed in reclaimed water: Characteristics, model for scale growth and metal element release.

Stainless steels generally have extremely good corrosion resistance, but are still susceptible to pitting corrosion. As a result, corrosion scales can form on the surface of stainless steel after extended exposure to aggressive aqueous environments. Corrosion scales play an important role in affecting water quality.

Dissecting the gene network of dietary restriction to identify evolutionarily conserved pathways and new functional genes.

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR.

Osh6 overexpression extends the lifespan of yeast by increasing vacuole fusion.

In yeast cells, the vacuole divides and fuses in each round of cell cycle. While mutants defective in vacuole fusion are "wild type" for vegetative growth, most have shortened replicative lifespans under caloric restriction (CR) condition, a manipulation that extends lifespan in wild type cells. To explore whether vacuole fusion extends lifespan, we screened for genes that can complement the fusion defect of selected mutants (erg6Δ, a sterol mutant; nyv1Δ,  a mutant involved in the vacuolar SNARE complex and vac8Δ, a vacuolar membrane protein mutant).

Designing dynamical output feedback controllers for store-operated Ca²+ entry.

Store-operated calcium entry (SOCE) has been proposed as the main process controlling Ca²+ entry in non-excitable cells. Although recent breakthroughs in experimental studies of SOCE have been made, its mathematical modeling has not been developed. In the present work, SOCE is viewed as a feedback control system subject to an extracellular agonist disturbance and an extracellular calcium input.

An age-dependent feedback control model of calcium dynamics in yeast cells.

The functional decline of selected proteins or organelles leads to aging at the intracellular level. Identification of these proteins or organelles is usually challenging to traditional single-factor approaches since these factors are inter-connected via feedback or feedforward controls. Establishing a feedback control model to simulate the interactions of multiple factors is an insightful approach to guide the search for proteins involved in aging.

A molecular mathematical model of glucose mobilization and uptake.

A new molecular mathematical model is developed by considering the kinetics of GLUT2, GLUT3, and GLUT4, the process of glucose mobilization by glycogen phosphorylase and glycogen synthase in liver, and the dynamics of the insulin signaling pathway. The new model can qualitatively reproduce the experimental glucose and insulin data. It also enables us to use the Bendixson criterion about the existence of periodic orbits of a two-dimensional dynamical system to mathematically predict that the oscillations of glucose and insulin are not caused by liver, instead they would be caused by the mechanism of insulin secretion from pancreatic beta cells.

Identification of longevity genes with systems biology approaches.

Identification of genes involved in the aging process is critical for understanding the mechanisms of age-dependent diseases such as cancer and diabetes. Measuring the mutant gene lifespan, each missing one gene, is traditionally employed to identify longevity genes. While such screening is impractical for the whole genome due to the time-consuming nature of lifespan assays, it can be achieved by in silico genetic manipulations with systems biology approaches.

PTC1 is required for vacuole inheritance and promotes the association of the myosin-V vacuole-specific receptor complex.

Organelle inheritance occurs during cell division. In Saccharomyces cerevisiae, inheritance of the vacuole, and the distribution of mitochondria and cortical endoplasmic reticulum are regulated by Ptc1p, a type 2C protein phosphatase. Here we show that PTC1/VAC10 controls the distribution of additional cargoes moved by a myosin-V motor.

A structural approach for finding functional modules from large biological networks.

Background: Biological systems can be modeled as complex network systems with many interactions between the components. These interactions give rise to the function and behavior of that system. For example, the protein-protein interaction network is the physical basis of multiple cellular functions.

A life-span extending form of autophagy employs the vacuole-vacuole fusion machinery.

While autophagy is believed to be beneficial for life-span extension, it is controversial which forms or aspects of autophagy are responsible for this effect. We addressed this topic by analyzing the life span of yeast autophagy mutants under caloric restriction, a longevity manipulation. Surprisingly, we discovered that the majority of proteins involved in macroautophagy and several forms of microautophagy were dispensable for life-span extension.

Modeling a simplified regulatory system of blood glucose at molecular levels.

In this paper, we propose a new mathematical control system for a simplified regulatory system of blood glucose by taking into account the dynamics of glucose and glycogen in liver and the dynamics of insulin and glucagon receptors at the molecular level. Numerical simulations show that the proposed feedback control system agrees approximately with published experimental data. Sensitivity analysis predicts that feedback control gains of insulin receptors and glucagon receptors are robust.

The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover.

Phosphoinositide-signaling lipids function in diverse cellular pathways. Dynamic changes in the levels of these signaling lipids regulate multiple processes. In particular, when Saccharomyces cerevisiae cells are exposed to hyperosmotic shock, PI3,5P2 (phosphatidylinositol [PI] 3,5-bisphosphate) levels transiently increase 20-fold.

Identification of an organelle-specific myosin V receptor.

Class V myosins are widely distributed among diverse organisms and move cargo along actin filaments. Some myosin Vs move multiple types of cargo, where the timing of movement and the destinations of selected cargoes are unique. Here, we report the discovery of an organelle-specific myosin V receptor.

Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole.

Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles.