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Search Results: 1 - 10 of 8356 matches for " Scott Tsuchiyama "
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A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan
Elizabeth X. Kwan,Eric J. Foss,Scott Tsuchiyama,Gina M. Alvino,Leonid Kruglyak,Matt Kaeberlein,M. K. Raghuraman,Bonita J. Brewer,Brian K. Kennedy,Antonio Bedalov
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003329
Abstract: Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics.
Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import
Chong He,Scott K. Tsuchiyama,Quynh T. Nguyen,Ekaterina N. Plyusnina,Samuel R. Terrill,Sarah Sahibzada,Bhumil Patel,Alena R. Faulkner,Mikhail V. Shaposhnikov,Ruilin Tian,Mitsuhiro Tsuchiya,Matt Kaeberlein,Alexey A. Moskalev,Brian K. Kennedy ,Michael Polymenis
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004860
Abstract: The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.
Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae
Undine Kruegel equal contributor,Brett Robison equal contributor,Thomas Dange,Günther Kahlert,Joe R. Delaney,Soumya Kotireddy,Mitsuhiro Tsuchiya,Scott Tsuchiyama,Christopher J. Murakami,Jennifer Schleit,George Sutphin,Daniel Carr,Krisztina Tar,Gunnar Dittmar,Matt Kaeberlein ,Brian K. Kennedy ,Marion Schmidt
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002253
Abstract: Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans.
Cadaveric Assessment of Synthetic Mid-Urethral Sling Placement  [PDF]
Scott Serels
Open Journal of Urology (OJU) , 2011, DOI: 10.4236/oju.2011.12006
Abstract: Purpose: To determine if 3 types of mid-urethral synthetic slings are visually the same. Materials and Methods: A retropubic, obturator, and single incision sling was individually placed in three cadavers. Tension was set using a spacer (obturator and retropubic). Single incision sling (SIS) tension was set by visual inspection. Thirty physicians were asked to determine placement method, tension, and location of the 3 slings. Results: Physicians were composed of 5 urologists, 7 urogynecologist, and 18 general gynecologists, with an average of 53 slings performed per year. Conclusion: This study showed that after placement of a sling it is hard to tell how the sling was placed and that most physicians felt the SIS was tensioned the best and most likely at the mid-urethra.
Cybersecurity: Integrating Information into the Microeconomics of the Consumer and the Firm  [PDF]
Scott Farrow
Journal of Information Security (JIS) , 2016, DOI: 10.4236/jis.2016.75023
Abstract: The connectivity of information has changed many things but not the way economists model consumers, firms and government. Information is here newly modeled as a fundamental element of microeconomic choices and utility, cost and tax functions. The results are more clearly defined metrics for losses due to cyber breaches or productivity gains from cyber investments. The integration of information into standard microeconomics also allows use of econometric and other tools to analyze the empirics of the consumer and the firm. In particular, the results identify ways in which losses in the Gordon and Loeb [1] model can be specified in more detail.
An Exploratory Survey of Sound Levels in New York City Restaurants and Bars  [PDF]
Gregory Scott
Open Journal of Social Sciences (JSS) , 2018, DOI: 10.4236/jss.2018.68005
Abstract: For several decades, there has been a significant need to better educate the public about noise pollution. A small number of small-scale studies have focused on the sound levels of restaurants and their impact on health and hearing. There have also been an increasing number of media articles stating that eating and drinking venues are getting increasingly loud making it more difficult for people to connect with others in conversation. This study reports on an exploratory large-scale noise survey of sound levels of 2376 restaurants and bars in New York City using a novel smart-phone application and categorized them based on how quiet or loud they were. The results suggest that: 1) A significant number of venues have high sound levels that are not conducive to conversation and may be endangering the health of patrons and employees, 2) that the reported sound levels by the venue managers on their online public business pages generally underestimated actual sound levels, and 3) the average sound levels in restaurants and bars are correlated by neighborhood and type of cuisine.
DNA Methylation Profiles of the Brain-Derived Neurotrophic Factor (BDNF) Gene as a Potent Diagnostic Biomarker in Major Depression
Manabu Fuchikami, Shigeru Morinobu, Masahiro Segawa, Yasumasa Okamoto, Shigeto Yamawaki, Norio Ozaki, Takeshi Inoue, Ichiro Kusumi, Tsukasa Koyama, Kounosuke Tsuchiyama, Takeshi Terao
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023881
Abstract: Major depression, because of its recurring and life-threatening nature, is one of the top 10 diseases for global disease burden. Major depression is still diagnosed on the basis of clinical symptoms in patients. The search for specific biological markers is of great importance to advance the method of diagnosis for depression. We examined the methylation profile of 2 CpG islands (I and IV) at the promoters of the brain-derived neurotrophic factor (BDNF) gene, which is well known to be involved in the pathophysiology of depression. We analyzed genomic DNA from peripheral blood of 20 Japanese patients with major depression and 18 healthy controls to identify an appropriate epigenetic biomarker to aid in the establishment of an objective system for the diagnosis of depression. Methylation rates at each CpG unit was measured using a MassArray? system (SEQUENOM), and 2-dimensional hierarchical clustering analyses were undertaken to determine the validity of these methylation profiles as a diagnostic biomarker. Analyses of the dendrogram from methylation profiles of CpG I, but not IV, demonstrated that classification of healthy controls and patients at the first branch completely matched the clinical diagnosis. Despite the small number of subjects, our results indicate that classification based on the DNA methylation profiles of CpG I of the BDNF gene may be a valuable diagnostic biomarker for major depression.
Bounds for Goal Achieving Probabilities of Mean-Variance Strategies with a No Bankruptcy Constraint  [PDF]
Alexandre Scott, Francois Watier
Applied Mathematics (AM) , 2012, DOI: 10.4236/am.2012.312A278
Abstract:

We establish, through solving semi-infinite programming problems, bounds on the probability of safely reaching a desired level of wealth on a finite horizon, when an investor starts with an optimal mean-variance financial investment strategy under a non-negative wealth restriction.

Regular menses at 73? A peculiar presentation of postmenopausal bleeding  [PDF]
Matthew McKnoulty, S. Scott
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.39125
Abstract:

Post menopausal bleeding is one of the most common conditions referred to gynaecology departments. Up to 5% of these women are found to have malignant, or pre-malignant lesions, with early detection and investigation being crucial for curative treatment. We report on the case of a 73-year-old women referred for having regular menses since 14 years of age and discuss the current investigation and management of post menopausal bleeding.

A Note on the Validity of the Shannon Formulation for Fitts’ Index of Difficulty  [PDF]
Ian Scott MacKenzie
Open Journal of Applied Sciences (OJAppS) , 2013, DOI: 10.4236/ojapps.2013.36046
Abstract:

The three most common variations of Fitts’ index of difficulty are the Fitts formulation, the Welford formulation, and the Shannon formulation. A recent paper by Hoffmann [1] critiqued the three and concluded that the Fitts and Welford formulations are valid and that the Shannon formulation is invalid. In this paper, we challenge Hoffmann’s position regarding the Shannon formulation. It is argued that the issue of validity vs. invalidity is ill-conceived, given that Fitts’ law is a “model by analogy” with no basis in human motor control. The relevant questions are of utility: Does a model work? How well? Is it useful? Where alternative formulations exist, they may be critiqued and compared for strengths and weaknesses, but validity is an irrelevant construct. In a reanalysis of data from Fitts’ law experiments, models built using the Shannon formulation are (re)affirmed to be as good as, and generally better than, those built using the Fitts or Welford formulation.

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