Fusheng Tang - Academia.edu (original) (raw)

Papers by Fusheng Tang

Research paper thumbnail of Localization of vacuole-related DR–essential proteins and lipids in yeast cells

<p>In response to environmental triggers such as DR, membrane transporters (Opt2 and others... more <p>In response to environmental triggers such as DR, membrane transporters (Opt2 and others) on the plasma membrane are endocytosed through lipid rafts (ergosterol-sphingolipids) after ubiquitinylation. On early endosomes, proteins and lipids are sorted to late endosomes, Golgi, or other organelles. In late endosomes, different endosomal sorting complexes required for transport (ESCRT) push the target proteins with their membranes into the lumen of late-endosome, or multivesicular bodies (MVB). Matured MVB can fuse with vacuoles, within which proteases and lipases (Atg15) degrade target proteins and lipids. In mammalian cells, maturation of late endosomes is essential for activation of the master regulator for growth, the mammalian target of rapamycin 1 (mTORC1). In yeast cells, TORC1 suppresses meiotic transcription factors which are normally only active during gametogenesis <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002834#pgen.1002834-Colomina1&quot; target="_blank">[110]</a>. The inhibitory effects of DR on TORC1 thus activate these rejuvenation genes. EE: early endosome. LE: late endosome. MVB: multivesicular body. Black arrows indicate movement of vesicles. DR-essential proteins are labelled in their localized organelles. Localization data were extracted from the SGD database. Ypt7 localization on late endosomes was reported by <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002834#pgen.1002834-Balderhaar1&quot; target="_blank">[111]</a>. Green arrows indicate activation and a red line indicates an inhibitory effect.</p

Research paper thumbnail of How can supervised machine learning algorithms be enhanced in their effectiveness to improve their predictive power by requiring proper feature selection; thus, advancing our understanding of still obscurely regulated complex phenomena, such as the gradual physiological decline due to aging?

Research paper thumbnail of Remote access programs to better integrate individuals with disabilities

2016 Research on Equity and Sustained Participation in Engineering, Computing, and Technology (RESPECT), 2016

Research paper thumbnail of Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles

Microbial Cell

Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between... more 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). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between OSH6 and DRS2, whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated OSH6 complemented vacuolar morphology of drs2∆ and enriched PI4P on the Golgi, indicating that Osh6 also works on the Golgi. This...

Research paper thumbnail of Identification of longevity genes with systems biology approaches

Advances and Applications in Bioinformatics and Chemistry, 2009

Identification of genes involved in the aging process is critical for understanding the mechanism... more 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. In this review, we will introduce pilot explorations applying two approaches of systems biology in aging studies. One approach is to predict the role of a specific gene in the aging process by comparing its expression profile and protein-protein interaction pattern with those of known longevity genes (top-down systems biology). The other approach is to construct mathematical models from previous kinetics data and predict how a specific protein contributes to aging and antiaging processes (bottom-up systems biology). These approaches allow researchers to simulate the effect of each gene's product in aging by in silico genetic manipulations such as deletion or over-expression. Since simulation-based approaches are not as widely used as the other approaches, we will focus our review on this effort in more detail. A combination of hypothesis from data-mining, in silico experimentation from simulations, and wet laboratory validation will make the systematic identification of all longevity genes possible.

Research paper thumbnail of JCB: ARTICLE <doi>10.1083/jcb.200512105</doi><aid>200512105</aid>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 l... more 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. This causes the vacuole to undergo multiple acute changes. Control of PI3,5P2 levels occurs through regulation of both its synthesis and turnover. Synthesis is catalyzed by the PI3P 5-kinase Fab1p, and turnover is catalyzed by the PI3,5P2 5-phosphatase

Research paper thumbnail of JCB Article Identification of an organelle-specific myosin V receptor

Class V myosins are widely distributed among diverse organisms and move cargo along actin filamen... more 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. Vac17p, a novel protein, is a component of the vacuole-specific receptor for Myo2p, a Saccharomyces cerevisiae myosin V. Vac17p interacts with the Myo2p cargo-binding domain, but not with vacuole inheritance-defective myo2 mutants that have single amino acid changes within this region. Moreover, a region of the

Research paper thumbnail of Vac8p, an Armadillo Repeat Protein, Coordinates Vacuole Inheritance With Multiple Vacuolar Processes

Vac8p, an armadillo (ARM) repeat protein, is required for multiple vacuolar processes. It functio... more Vac8p, an armadillo (ARM) repeat protein, is required for multiple vacuolar processes. It functions in vacuole inher-itance, cytoplasm-to-vacuole protein targeting pathway, formation of the nucleus–vacuole junction and vacuole– vacuole fusion. These functions each utilize a distinct Vac8p-binding partner. Here, we report an additional Vac8p function: caffeine resistance. We show that Vac8p function in caffeine resistance is mediated via a newly identified Vac8p-binding partner, Tco89p. The interaction between Vac8p and each binding partner requires an overlapping subset of Vac8p ARM repeats. Moreover, these partners can compete with each other for access to Vac8p. Furthermore, Vac8p is enriched in three sepa-rate subdomains on the vacuole, each with a unique binding partner dedicated to a different vacuolar func-tion. These findings suggest that a major role of Vac8p is to spatially separate multiple functions thereby enabling vacuole inheritance to occur concurrently with other vac...

Research paper thumbnail of Stainless steel corrosion scale formed in reclaimed water: Characteristics, model for scale growth and metal element release

Journal of Environmental Sciences, 2016

Stainless steels generally have extremely good corrosion resistance, but are still susceptible to... more 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. These research results showed that interior regions of stainless steel corrosion scales have a high percentage of chromium phases. We reveal the morphology, micro-structure and physicochemical characteristics of stainless steel corrosion scales. Stainless steel corrosion scale is identified as a podiform chromite deposit according to these characteristics, which is unlike deposit formed during iron corrosion. A conceptual model to explain the formation and growth of stainless steel corrosion scale is proposed based on its composition and structure. The scale growth process involves pitting corrosion on the stainless steel surface and the consecutive generation and homogeneous deposition of corrosion products, which is governed by a series of chemical and electrochemical reactions. This model shows the role of corrosion scales in the mechanism of iron and chromium release from pitting corroded stainless steel materials. The formation of corrosion scale is strongly related to water quality parameters. The presence of HClO results in higher ferric content inside the scales. Cl(-) and SO4(2-) ions in reclaimed water play an important role in corrosion pitting of stainless steel and promote the formation of scales.

Research paper thumbnail of An output feedback controller for store-operated calcium entry and extracellular calcium sensing in yeast cells

2010 Chinese Control and Decision Conference, 2010

Store-operated calcium entry (SOCE) and extracellular calcium sensing are two important feedback ... more Store-operated calcium entry (SOCE) and extracellular calcium sensing are two important feedback control mechanisms of calcium ion uptake into yeast cells observed in experiments. In this work, we design output feedback controllers for these two mechanisms. Using the control model, we simulate the experimental observations on these two mechanisms and on high-affinity calcium ion influx system in pmr1 mutants.

Research paper thumbnail of A molecular mathematical model of glucose mobilization and uptake

Mathematical Biosciences, 2009

A new molecular mathematical model is developed by considering the kinetics of GLUT2, GLUT3, and ... more 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 b cells. Furthermore it enables us to conduct a parametric sensitivity analysis. The analysis shows that both glucose and insulin are most sensitive to the rate constant for conversion of PI(3, 4, 5)P 3 to PI(4, 5)P 2 , the multiplicative factor modulating the rate constant for conversion of PI(3, 4, 5)P 3 to PI(4, 5)P 2 , the multiplicative factor that modulates insulin receptor dephosphorylation rate, and the maximum velocity of GLUT4. Moreover, the sensitivity analysis predicts that an increase of the apparent velocity of GLUT4, a combination of elevated mobilization rate of GLUT4 to the plasma membrane and an extended duration of GLUT4 on the plasma membrane, will result in a decrease in the needs of plasma insulin. On the other hand, an increase of the GLUT4 internalization rate results in an elevated demand of insulin to stimulate the mobilization of GLUT4 from the intracellular store to the plasma membrane.

Research paper thumbnail of Modeling a simplified regulatory system of blood glucose at molecular levels

Journal of Theoretical Biology, 2008

In this paper, we propose a new mathematical control system for a simplified regulatory system of... more 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. Using the model, we develop a new formula to compute the insulin sensitivity. The formula shows that the insulin sensitivity depends on various parameters that determine the insulin influence on insulin-dependent glucose utilization and reflect the efficiency of binding of insulin to its receptors. Using Lyapunov indirect method, we prove that the new control system is input-output stable. The stability result provides theoretical evidence for the phenomenon that the blood glucose fluctuates within a narrow range in response to the exogenous glucose input from food. We also show that the regulatory system is controllable and observable. These structural system properties could explain why the glucose level can be regulated. Published by Elsevier Ltd.

Research paper thumbnail of An age-dependent feedback control model of calcium dynamics in yeast cells

Journal of Mathematical Biology, 2010

The functional decline of selected proteins or organelles leads to aging at the intracellular lev... more 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. However, there are only a few mathematical models describing the age-dependent accumulation of DNA mutations, which are directly or indirectly induced by deterioration of the intracellular environment including alteration of calcium homeostasis, a contributor of aging. Thus, based on Cui and Kaandorp's model, we develop an age-dependent mathematical model for the calcium homeostasis in budding yeast Saccharomyces cerevisiae. Our model contains cell cycle-dependent aging factors and can qualitatively reproduce calcium shocks and calcium accumulations in cells observed in experiments. Using this model, we predict calcium oscillations in wild type, pmc1 , and pmr1 cells. This prediction suggests that Pmr1p plays a major role in regulating cytosolic calcium. Combining the model with our experimental lifespan data, we predict an upper-limit of cytosolic calcium tolerance for cell survival. This prediction indicates that, for aged cells (>35 generations), no pmr1 can tolerate the cytosolic calcium concentration of 0.1 µM while a very small fraction (1%) of aged wild type cells (>50 generations) can tolerate a high cytosolic calcium concentration of 0.5 µM.

Research paper thumbnail of Osh6 overexpression extends the lifespan of yeast by increasing vacuole fusion

Cell Cycle, 2012

In yeast cells, the vacuole divides and fuses in each round of cell cycle. While mutants defectiv... more In yeast cells, the vacuole divides and fuses in each round of cell cycle. While mutants defective in vacuole fusion are &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;wild type&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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). This screen revealed that Osh6, a member of the oxysterol-binding protein family, can complement the vacuole fusion defect of nyv1Δ, but not erg6Δ or vac8Δ, suggesting that Osh6&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s function in vacuole fusion is partly dependent on membrane ergosterol and Vac8. To measure the effect of OSH6 on lifespan, we replaced the endogenous promoter of OSH6 with a shorter version of the ERG6 promoter to obtain PERG6-OSH6. This mutant construct significantly extended the replicative lifespan in a wild type background and in a nyv1Δ mutant. Interestingly, PERG6-OSH6 cells were more sensitive to drugs that inhibit the activity of the TOR complex 1 (TORC1) than wild type cells. Moreover, a PERG6-OSH6 tor1Δ double mutant demonstrated a greatly shortened lifespan, suggesting a genetic interaction between Osh6 and Tor1. Since active TORC1 stimulates vacuole scission and CR downregulates TORC1, Osh6 may link these two pathways by adjusting vacuolar membrane organization to extend lifespan.

Research paper thumbnail of Identification of longevity genes with systems biology approaches

Advances and Applications in Bioinformatics and Chemistry Aabc, 2009

Identification of genes involved in the aging process is critical for understanding the mechanism... more 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. In this review, we will introduce pilot explorations applying two approaches of systems biology in aging studies. One approach is to predict the role of a specific gene in the aging process by comparing its expression profile and protein–protein interaction pattern with those of known longevity genes (top-down systems biology). The other approach is to construct mathematical models from previous kinetics data and predict how a specific protein contributes to aging and antiaging processes (bottom-up systems biology). These approaches allow researchers to simulate the effect of each gene’s product in aging by in silico genetic manipulations such as deletion or over-expression. Since simulation-based approaches are not as widely used as the other approaches, we will focus our review on this effort in more detail. A combination of hypothesis from data-mining, in silico experimentation from simulations, and wet laboratory validation will make the systematic identification of all longevity genes possible.

Research paper thumbnail of Preparation and piezoelectric properties of (K0.5Na0.5)NbO3 lead-free piezoelectric ceramics with pressure-less sintering

Materials Science Engineering B Solid State Materials For Advanced Technology, 2006

Lead-free piezoelectric ceramics (K 0.5 Na 0.5 )NbO 3 (abbreviated as KNN) with the relative dens... more Lead-free piezoelectric ceramics (K 0.5 Na 0.5 )NbO 3 (abbreviated as KNN) with the relative density of 97.6% have been synthesized by press-less sintering owing to the careful control of processing conditions. The phase structure of KNN ceramics with different sintering temperature and heating rate was analyzed. Results show that the pure perovskite phase with orthorhombic symmetry is in all ceramics specimens. The effect of heating rate and sintering temperature on microstructure and piezoelectric properties of KNN ceramics was investigated. The densification behavior and piezoelectric properties of KNN ceramics were enhanced by improving heating rate and sintering temperature. Pure KNN ceramics sintered at 1120 • C with heating rate of 5 • C/min showed optimized densification and piezoelectric properties (ρ = 4.4 g/cm 3 , d 33 = 120 pC/N −1 , k p = 0.40 and T c = 400 • C). The results show that KNN is a promising candidate for lead-free piezoelectric ceramics.

Research paper thumbnail of The Vac14p-Fig4p complex acts independently of Vac7p and couples P13,5P2 synthesis and turnover

The Journal of Cell Biology, 2006

P hosphoinositide-signaling lipids function in diverse cellular pathways. Dynamic changes in the ... more P hosphoinositide-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, PI3,5P 2 (phosphatidylinositol [PI] 3,5-bisphosphate) levels transiently increase 20-fold. This causes the vacuole to undergo multiple acute changes. Control of PI3,5P 2 levels occurs through regulation of both its synthesis and turnover. Synthesis is catalyzed by the PI3P 5-kinase Fab1p, and turnover is catalyzed by the PI3,5P 2 5-phosphatase Fig4p. In this study, we show that two putative Fab1p activators, Vac7p and Vac14p, independently regulate Fab1p activity. Although Vac7p only regulates Fab1p, surprisingly, we fi nd that Vac14 regulates both Fab1p and Fig4p. Moreover, Fig4p itself functions in both PI3,5P 2 synthesis and turnover. In both the absence and presence of Vac7p, the Vac14p-Fig4p complex controls the hyperosmotic shock-induced increase in PI3,5P 2 levels.

Research paper thumbnail of Influence of sintering temperature on piezoelectric properties of (K0.5Na0.5)NbO3–LiNbO3 lead-free piezoelectric ceramics

Materials Research Bulletin, Sep 1, 2007

Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditiona... more Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditional ceramics process without cold-isostatic pressing. The effect of the content of LiNbO3 and the sintering temperature on the phase structure, the microstructure and piezoelectric properties of (1−x)(K0.5Na0.5)NbO3–xLiNbO3 ceramics were investigated. The result shows that the phase structure transforms from the orthorhombic phase to tetragonal phase with the increase of the content

Research paper thumbnail of The Microstructure and Ferroelectric Properties of (K0.5Na0.5)NbO3–LiNbO3 Lead-Free Piezoelectric Ceramics

Materials Science and Engineering B

Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditiona... more Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditional ceramics process without cold-isostatic pressing. Effect of the amount of LiNbO3 on the phase structure, microstructure, ferroelectric and piezoelectric properties of (1−x)(K0.5Na0.5)NbO3–xLiNbO3 ceramics were investigated. Results show that the pure perovskite phase is in all ceramics specimens (x&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.08). With the content of LiNbO3 increases, remnant polarization Pr, coercive field Ec and

Research paper thumbnail of A structural approach for finding functional modules from large biological networks

Background: Biological systems can be modeled as complex network systems with many interactions b... more 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. One goal of emerging systems biology is to analyze very large complex biological networks such as protein-protein interaction networks, metabolic networks, and regulatory networks to identify functional modules and assign functions to certain components of the system. Network modules do not occur by chance, so identification of modules is likely to capture the biologically meaningful interactions in large-scale PPI data. Unfortunately, existing computer-based clustering methods developed to find those modules are either not so accurate or too slow.

Research paper thumbnail of Localization of vacuole-related DR–essential proteins and lipids in yeast cells

<p>In response to environmental triggers such as DR, membrane transporters (Opt2 and others... more <p>In response to environmental triggers such as DR, membrane transporters (Opt2 and others) on the plasma membrane are endocytosed through lipid rafts (ergosterol-sphingolipids) after ubiquitinylation. On early endosomes, proteins and lipids are sorted to late endosomes, Golgi, or other organelles. In late endosomes, different endosomal sorting complexes required for transport (ESCRT) push the target proteins with their membranes into the lumen of late-endosome, or multivesicular bodies (MVB). Matured MVB can fuse with vacuoles, within which proteases and lipases (Atg15) degrade target proteins and lipids. In mammalian cells, maturation of late endosomes is essential for activation of the master regulator for growth, the mammalian target of rapamycin 1 (mTORC1). In yeast cells, TORC1 suppresses meiotic transcription factors which are normally only active during gametogenesis <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002834#pgen.1002834-Colomina1&quot; target="_blank">[110]</a>. The inhibitory effects of DR on TORC1 thus activate these rejuvenation genes. EE: early endosome. LE: late endosome. MVB: multivesicular body. Black arrows indicate movement of vesicles. DR-essential proteins are labelled in their localized organelles. Localization data were extracted from the SGD database. Ypt7 localization on late endosomes was reported by <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002834#pgen.1002834-Balderhaar1&quot; target="_blank">[111]</a>. Green arrows indicate activation and a red line indicates an inhibitory effect.</p

Research paper thumbnail of How can supervised machine learning algorithms be enhanced in their effectiveness to improve their predictive power by requiring proper feature selection; thus, advancing our understanding of still obscurely regulated complex phenomena, such as the gradual physiological decline due to aging?

Research paper thumbnail of Remote access programs to better integrate individuals with disabilities

2016 Research on Equity and Sustained Participation in Engineering, Computing, and Technology (RESPECT), 2016

Research paper thumbnail of Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles

Microbial Cell

Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between... more 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). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between OSH6 and DRS2, whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated OSH6 complemented vacuolar morphology of drs2∆ and enriched PI4P on the Golgi, indicating that Osh6 also works on the Golgi. This...

Research paper thumbnail of Identification of longevity genes with systems biology approaches

Advances and Applications in Bioinformatics and Chemistry, 2009

Identification of genes involved in the aging process is critical for understanding the mechanism... more 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. In this review, we will introduce pilot explorations applying two approaches of systems biology in aging studies. One approach is to predict the role of a specific gene in the aging process by comparing its expression profile and protein-protein interaction pattern with those of known longevity genes (top-down systems biology). The other approach is to construct mathematical models from previous kinetics data and predict how a specific protein contributes to aging and antiaging processes (bottom-up systems biology). These approaches allow researchers to simulate the effect of each gene's product in aging by in silico genetic manipulations such as deletion or over-expression. Since simulation-based approaches are not as widely used as the other approaches, we will focus our review on this effort in more detail. A combination of hypothesis from data-mining, in silico experimentation from simulations, and wet laboratory validation will make the systematic identification of all longevity genes possible.

Research paper thumbnail of JCB: ARTICLE <doi>10.1083/jcb.200512105</doi><aid>200512105</aid>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 l... more 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. This causes the vacuole to undergo multiple acute changes. Control of PI3,5P2 levels occurs through regulation of both its synthesis and turnover. Synthesis is catalyzed by the PI3P 5-kinase Fab1p, and turnover is catalyzed by the PI3,5P2 5-phosphatase

Research paper thumbnail of JCB Article Identification of an organelle-specific myosin V receptor

Class V myosins are widely distributed among diverse organisms and move cargo along actin filamen... more 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. Vac17p, a novel protein, is a component of the vacuole-specific receptor for Myo2p, a Saccharomyces cerevisiae myosin V. Vac17p interacts with the Myo2p cargo-binding domain, but not with vacuole inheritance-defective myo2 mutants that have single amino acid changes within this region. Moreover, a region of the

Research paper thumbnail of Vac8p, an Armadillo Repeat Protein, Coordinates Vacuole Inheritance With Multiple Vacuolar Processes

Vac8p, an armadillo (ARM) repeat protein, is required for multiple vacuolar processes. It functio... more Vac8p, an armadillo (ARM) repeat protein, is required for multiple vacuolar processes. It functions in vacuole inher-itance, cytoplasm-to-vacuole protein targeting pathway, formation of the nucleus–vacuole junction and vacuole– vacuole fusion. These functions each utilize a distinct Vac8p-binding partner. Here, we report an additional Vac8p function: caffeine resistance. We show that Vac8p function in caffeine resistance is mediated via a newly identified Vac8p-binding partner, Tco89p. The interaction between Vac8p and each binding partner requires an overlapping subset of Vac8p ARM repeats. Moreover, these partners can compete with each other for access to Vac8p. Furthermore, Vac8p is enriched in three sepa-rate subdomains on the vacuole, each with a unique binding partner dedicated to a different vacuolar func-tion. These findings suggest that a major role of Vac8p is to spatially separate multiple functions thereby enabling vacuole inheritance to occur concurrently with other vac...

Research paper thumbnail of Stainless steel corrosion scale formed in reclaimed water: Characteristics, model for scale growth and metal element release

Journal of Environmental Sciences, 2016

Stainless steels generally have extremely good corrosion resistance, but are still susceptible to... more 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. These research results showed that interior regions of stainless steel corrosion scales have a high percentage of chromium phases. We reveal the morphology, micro-structure and physicochemical characteristics of stainless steel corrosion scales. Stainless steel corrosion scale is identified as a podiform chromite deposit according to these characteristics, which is unlike deposit formed during iron corrosion. A conceptual model to explain the formation and growth of stainless steel corrosion scale is proposed based on its composition and structure. The scale growth process involves pitting corrosion on the stainless steel surface and the consecutive generation and homogeneous deposition of corrosion products, which is governed by a series of chemical and electrochemical reactions. This model shows the role of corrosion scales in the mechanism of iron and chromium release from pitting corroded stainless steel materials. The formation of corrosion scale is strongly related to water quality parameters. The presence of HClO results in higher ferric content inside the scales. Cl(-) and SO4(2-) ions in reclaimed water play an important role in corrosion pitting of stainless steel and promote the formation of scales.

Research paper thumbnail of An output feedback controller for store-operated calcium entry and extracellular calcium sensing in yeast cells

2010 Chinese Control and Decision Conference, 2010

Store-operated calcium entry (SOCE) and extracellular calcium sensing are two important feedback ... more Store-operated calcium entry (SOCE) and extracellular calcium sensing are two important feedback control mechanisms of calcium ion uptake into yeast cells observed in experiments. In this work, we design output feedback controllers for these two mechanisms. Using the control model, we simulate the experimental observations on these two mechanisms and on high-affinity calcium ion influx system in pmr1 mutants.

Research paper thumbnail of A molecular mathematical model of glucose mobilization and uptake

Mathematical Biosciences, 2009

A new molecular mathematical model is developed by considering the kinetics of GLUT2, GLUT3, and ... more 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 b cells. Furthermore it enables us to conduct a parametric sensitivity analysis. The analysis shows that both glucose and insulin are most sensitive to the rate constant for conversion of PI(3, 4, 5)P 3 to PI(4, 5)P 2 , the multiplicative factor modulating the rate constant for conversion of PI(3, 4, 5)P 3 to PI(4, 5)P 2 , the multiplicative factor that modulates insulin receptor dephosphorylation rate, and the maximum velocity of GLUT4. Moreover, the sensitivity analysis predicts that an increase of the apparent velocity of GLUT4, a combination of elevated mobilization rate of GLUT4 to the plasma membrane and an extended duration of GLUT4 on the plasma membrane, will result in a decrease in the needs of plasma insulin. On the other hand, an increase of the GLUT4 internalization rate results in an elevated demand of insulin to stimulate the mobilization of GLUT4 from the intracellular store to the plasma membrane.

Research paper thumbnail of Modeling a simplified regulatory system of blood glucose at molecular levels

Journal of Theoretical Biology, 2008

In this paper, we propose a new mathematical control system for a simplified regulatory system of... more 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. Using the model, we develop a new formula to compute the insulin sensitivity. The formula shows that the insulin sensitivity depends on various parameters that determine the insulin influence on insulin-dependent glucose utilization and reflect the efficiency of binding of insulin to its receptors. Using Lyapunov indirect method, we prove that the new control system is input-output stable. The stability result provides theoretical evidence for the phenomenon that the blood glucose fluctuates within a narrow range in response to the exogenous glucose input from food. We also show that the regulatory system is controllable and observable. These structural system properties could explain why the glucose level can be regulated. Published by Elsevier Ltd.

Research paper thumbnail of An age-dependent feedback control model of calcium dynamics in yeast cells

Journal of Mathematical Biology, 2010

The functional decline of selected proteins or organelles leads to aging at the intracellular lev... more 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. However, there are only a few mathematical models describing the age-dependent accumulation of DNA mutations, which are directly or indirectly induced by deterioration of the intracellular environment including alteration of calcium homeostasis, a contributor of aging. Thus, based on Cui and Kaandorp's model, we develop an age-dependent mathematical model for the calcium homeostasis in budding yeast Saccharomyces cerevisiae. Our model contains cell cycle-dependent aging factors and can qualitatively reproduce calcium shocks and calcium accumulations in cells observed in experiments. Using this model, we predict calcium oscillations in wild type, pmc1 , and pmr1 cells. This prediction suggests that Pmr1p plays a major role in regulating cytosolic calcium. Combining the model with our experimental lifespan data, we predict an upper-limit of cytosolic calcium tolerance for cell survival. This prediction indicates that, for aged cells (>35 generations), no pmr1 can tolerate the cytosolic calcium concentration of 0.1 µM while a very small fraction (1%) of aged wild type cells (>50 generations) can tolerate a high cytosolic calcium concentration of 0.5 µM.

Research paper thumbnail of Osh6 overexpression extends the lifespan of yeast by increasing vacuole fusion

Cell Cycle, 2012

In yeast cells, the vacuole divides and fuses in each round of cell cycle. While mutants defectiv... more In yeast cells, the vacuole divides and fuses in each round of cell cycle. While mutants defective in vacuole fusion are &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;wild type&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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). This screen revealed that Osh6, a member of the oxysterol-binding protein family, can complement the vacuole fusion defect of nyv1Δ, but not erg6Δ or vac8Δ, suggesting that Osh6&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s function in vacuole fusion is partly dependent on membrane ergosterol and Vac8. To measure the effect of OSH6 on lifespan, we replaced the endogenous promoter of OSH6 with a shorter version of the ERG6 promoter to obtain PERG6-OSH6. This mutant construct significantly extended the replicative lifespan in a wild type background and in a nyv1Δ mutant. Interestingly, PERG6-OSH6 cells were more sensitive to drugs that inhibit the activity of the TOR complex 1 (TORC1) than wild type cells. Moreover, a PERG6-OSH6 tor1Δ double mutant demonstrated a greatly shortened lifespan, suggesting a genetic interaction between Osh6 and Tor1. Since active TORC1 stimulates vacuole scission and CR downregulates TORC1, Osh6 may link these two pathways by adjusting vacuolar membrane organization to extend lifespan.

Research paper thumbnail of Identification of longevity genes with systems biology approaches

Advances and Applications in Bioinformatics and Chemistry Aabc, 2009

Identification of genes involved in the aging process is critical for understanding the mechanism... more 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. In this review, we will introduce pilot explorations applying two approaches of systems biology in aging studies. One approach is to predict the role of a specific gene in the aging process by comparing its expression profile and protein–protein interaction pattern with those of known longevity genes (top-down systems biology). The other approach is to construct mathematical models from previous kinetics data and predict how a specific protein contributes to aging and antiaging processes (bottom-up systems biology). These approaches allow researchers to simulate the effect of each gene’s product in aging by in silico genetic manipulations such as deletion or over-expression. Since simulation-based approaches are not as widely used as the other approaches, we will focus our review on this effort in more detail. A combination of hypothesis from data-mining, in silico experimentation from simulations, and wet laboratory validation will make the systematic identification of all longevity genes possible.

Research paper thumbnail of Preparation and piezoelectric properties of (K0.5Na0.5)NbO3 lead-free piezoelectric ceramics with pressure-less sintering

Materials Science Engineering B Solid State Materials For Advanced Technology, 2006

Lead-free piezoelectric ceramics (K 0.5 Na 0.5 )NbO 3 (abbreviated as KNN) with the relative dens... more Lead-free piezoelectric ceramics (K 0.5 Na 0.5 )NbO 3 (abbreviated as KNN) with the relative density of 97.6% have been synthesized by press-less sintering owing to the careful control of processing conditions. The phase structure of KNN ceramics with different sintering temperature and heating rate was analyzed. Results show that the pure perovskite phase with orthorhombic symmetry is in all ceramics specimens. The effect of heating rate and sintering temperature on microstructure and piezoelectric properties of KNN ceramics was investigated. The densification behavior and piezoelectric properties of KNN ceramics were enhanced by improving heating rate and sintering temperature. Pure KNN ceramics sintered at 1120 • C with heating rate of 5 • C/min showed optimized densification and piezoelectric properties (ρ = 4.4 g/cm 3 , d 33 = 120 pC/N −1 , k p = 0.40 and T c = 400 • C). The results show that KNN is a promising candidate for lead-free piezoelectric ceramics.

Research paper thumbnail of The Vac14p-Fig4p complex acts independently of Vac7p and couples P13,5P2 synthesis and turnover

The Journal of Cell Biology, 2006

P hosphoinositide-signaling lipids function in diverse cellular pathways. Dynamic changes in the ... more P hosphoinositide-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, PI3,5P 2 (phosphatidylinositol [PI] 3,5-bisphosphate) levels transiently increase 20-fold. This causes the vacuole to undergo multiple acute changes. Control of PI3,5P 2 levels occurs through regulation of both its synthesis and turnover. Synthesis is catalyzed by the PI3P 5-kinase Fab1p, and turnover is catalyzed by the PI3,5P 2 5-phosphatase Fig4p. In this study, we show that two putative Fab1p activators, Vac7p and Vac14p, independently regulate Fab1p activity. Although Vac7p only regulates Fab1p, surprisingly, we fi nd that Vac14 regulates both Fab1p and Fig4p. Moreover, Fig4p itself functions in both PI3,5P 2 synthesis and turnover. In both the absence and presence of Vac7p, the Vac14p-Fig4p complex controls the hyperosmotic shock-induced increase in PI3,5P 2 levels.

Research paper thumbnail of Influence of sintering temperature on piezoelectric properties of (K0.5Na0.5)NbO3–LiNbO3 lead-free piezoelectric ceramics

Materials Research Bulletin, Sep 1, 2007

Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditiona... more Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditional ceramics process without cold-isostatic pressing. The effect of the content of LiNbO3 and the sintering temperature on the phase structure, the microstructure and piezoelectric properties of (1−x)(K0.5Na0.5)NbO3–xLiNbO3 ceramics were investigated. The result shows that the phase structure transforms from the orthorhombic phase to tetragonal phase with the increase of the content

Research paper thumbnail of The Microstructure and Ferroelectric Properties of (K0.5Na0.5)NbO3–LiNbO3 Lead-Free Piezoelectric Ceramics

Materials Science and Engineering B

Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditiona... more Lead-free piezoelectric ceramics (1−x)(K0.5Na0.5)NbO3–xLiNbO3 have been synthesized by traditional ceramics process without cold-isostatic pressing. Effect of the amount of LiNbO3 on the phase structure, microstructure, ferroelectric and piezoelectric properties of (1−x)(K0.5Na0.5)NbO3–xLiNbO3 ceramics were investigated. Results show that the pure perovskite phase is in all ceramics specimens (x&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.08). With the content of LiNbO3 increases, remnant polarization Pr, coercive field Ec and

Research paper thumbnail of A structural approach for finding functional modules from large biological networks

Background: Biological systems can be modeled as complex network systems with many interactions b... more 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. One goal of emerging systems biology is to analyze very large complex biological networks such as protein-protein interaction networks, metabolic networks, and regulatory networks to identify functional modules and assign functions to certain components of the system. Network modules do not occur by chance, so identification of modules is likely to capture the biologically meaningful interactions in large-scale PPI data. Unfortunately, existing computer-based clustering methods developed to find those modules are either not so accurate or too slow.