Multiomics of -Dependent Replicative Lifespan Extension Models Reveals Gcn4 as a Regulator of Protein Turnover in Yeast.

We have shown that multiple tRNA synthetase inhibitors can increase lifespan in both the nematode and the budding yeast by acting through the conserved transcription factor Gcn4 (yeast)/ATF-4 (worms). To further understand the biology downstream from this conserved transcription factor in the yeast model system, we looked at two different yeast models known to have upregulated Gcn4 and -dependent increased replicative lifespan. These two models were yeast and yeast treated with the tRNA synthetase inhibitor borrelidin.

Mapping interactions of calmodulin and neuronal NO synthase by crosslinking and mass spectrometry.

Neuronal nitric oxide synthase (nNOS) is a homodimeric cytochrome P450-like enzyme that catalyzes the conversion of L-arginine to nitric oxide in the presence of NADPH and molecular oxygen. The binding of calmodulin (CaM) to a linker region between the FAD/FMN-containing reductase domain, and the heme-containing oxygenase domain is needed for electron transfer reactions, reduction of the heme, and NO synthesis. Due to the dynamic nature of the reductase domain and low resolution of available full-length structures, the exact conformation of the CaM-bound active complex during heme reduction is still unresolved.

Mapping protein-protein interactions in homodimeric CYP102A1 by crosslinking and mass spectrometry.

Covalent crosslinking and mass spectrometry techniques hold great potential in the study of multiprotein complexes, but a major challenge is the inability to differentiate intra- and inter- protein crosslinks in homomeric complexes. In the current study we use CYP102A1, a well-characterized homodimeric P450, to examine a subtractive method that utilizes limited crosslinking with disuccinimidyl dibutyric urea (DSBU) and isolation of the monomer, in addition to the crosslinked dimer, to identify inter-monomer crosslinks. The utility of this approach was examined with the use of MS-cleavable crosslinker DSBU and recently published cryo-EM based structures of the CYP102A1 homodimer.

SPOCK, an R based package for high-throughput analysis of growth rate, survival, and chronological lifespan in yeast.

Plate reader-based methods for high-throughput measurement of growth rate, cellular survival, and chronological lifespan are a compelling addition to the already powerful toolbox of budding yeast genetics. These methods have overcome many of the limits of traditional yeast biology techniques, but also present a new bottleneck at the point of data-analysis. Herein, we describe SPOCK (Survival Percentage and Outgrowth Collection Kit), an R-based package for the analysis of data created by high-throughput plate reader based methods.

lifespan measurement.

Aging is a fundamental biological process that is still not fully understood. As many of the most significant human diseases have aging as their greatest risk factor, a better understanding of aging potentially has enormous practical implications in treating these diseases. The nematode is an exceptionally useful genetic model organism that had been used with great success to shed light on many genes and pathways that are involved in aging.

Adsorption of Malathion onto Copper and Iron Surfaces Relevant to Water Infrastructure.

This study investigated the adsorption of malathion to copper and iron surfaces including microspheres and pipe specimens similar to those in drinking water infrastructure. The solid phase concentration of malathion on the virgin and used copper pipe specimens was generally between 0.2 - 1 mg/g.

Evaluation of relational and NoSQL database architectures to manage genomic annotations.

While the adoption of next generation sequencing has rapidly expanded, the informatics infrastructure used to manage the data generated by this technology has not kept pace. Historically, relational databases have provided much of the framework for data storage and retrieval. Newer technologies based on NoSQL architectures may provide significant advantages in storage and query efficiency, thereby reducing the cost of data management.

Laboratory evaluation of airborne particulate control treatments for simulated aircraft crash recovery operations involving carbon fiber composite materials.

Objective: This study compared four treatment protocols to reduce airborne composite fiber particulates during simulated aircraft crash recovery operations.

Design: Four different treatments were applied to determine effectiveness in reducing airborne composite fiber particulates as compared to a "no treatment" protocol. Both "gold standard" gravimetric methods and real-time instruments were used to describe mass per volume concentration, particle size distribution, and surface area.

Laboratory evaluation of airborne particulate control treatments for simulated aircraft crash recovery operations involving carbon fiber composite materials.

Objective: This study compared four treatment protocols to reduce airborne composite fiber particulates during simulated aircraft crash recovery operations.

Design: Four different treatments were applied to determine effectiveness in reducing airborne composite fiber particulates as compared to a "no treatment" protocol. Both "gold standard" gravimetric methods and real-time instruments were used to describe mass per volume concentration, particle size distribution, and surface area.

Comparison of high-volume air sampling equipment for viral aerosol sampling during emergency response.

Objective: This study compared the performance of two high-volume bioaerosol air samplers for viable virus to an accepted standard low-volume sampler. In typical bioaerosol emergency response scenarios, highvolume sampling is essential for the low infective concentrations and large air volumes involved.

Design: Two high-volume air samplers (XMX/2LMIL and DFU-1000) were evaluated alongside a lowvolume sample (BioSampler).

Fate of malathion and a phosphonic acid in activated sludge with varying solids retention times.

This study examined the ability of activated sludge (AS) to sorb and biodegrade ethylmethylphosphonic acid (EMPA) and malathion, a degradation product and surrogate, respectively, for an organophosphate chemical warfare agent. Sorption equilibrium isotherm experiments indicate that sorption of EMPA and malathion to AS is negligible. EMPA at a concentration of 1 mg L(-1) degraded by approximately 30% with apparent first-order kinetics, possibly via co-metabolism from nitrification.

Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity.

Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world. Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients. This adverse effect does not display normal dose-response curves and can be lethal in children.

Nanoscale structural and mechanical analysis of Bacillus anthracis spores inactivated with rapid dry heating.

Effective killing of Bacillus anthracis spores is of paramount importance to antibioterrorism, food safety, environmental protection, and the medical device industry. Thus, a deeper understanding of the mechanisms of spore resistance and inactivation is highly desired for developing new strategies or improving the known methods for spore destruction. Previous studies have shown that spore inactivation mechanisms differ considerably depending upon the killing agents, such as heat (wet heat, dry heat), UV, ionizing radiation, and chemicals.

Evaluating the abnormal ossification in tibiotarsi of developing chick embryos exposed to 1.0ppm doses of platinum group metals by spectroscopic techniques.

Platinum group metals (PGMs), i.e., palladium (Pd), platinum (Pt) and rhodium (Rh), are found at pollutant levels in the environment and are known to accumulate in plant and animal tissues.

Enhancement of ferroelectric polarization stability by interface engineering.

By using theoretical predictions based on first-principle calculations, we explore an interface engineering approach to stabilize polarization states in ferroelectric heterostructures with a thickness of just several nanometers.

Giant piezoelectricity on Si for hyperactive MEMS.

Microelectromechanical systems (MEMS) incorporating active piezoelectric layers offer integrated actuation, sensing, and transduction. The broad implementation of such active MEMS has long been constrained by the inability to integrate materials with giant piezoelectric response, such as Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) (PMN-PT). We synthesized high-quality PMN-PT epitaxial thin films on vicinal (001) Si wafers with the use of an epitaxial (001) SrTiO(3) template layer with superior piezoelectric coefficients (e(31,f) = -27 ± 3 coulombs per square meter) and figures of merit for piezoelectric energy-harvesting systems.

Metallic and insulating oxide interfaces controlled by electronic correlations.

The formation of two-dimensional electron gases (2DEGs) at complex oxide interfaces is directly influenced by the oxide electronic properties. We investigated how local electron correlations control the 2DEG by inserting a single atomic layer of a rare-earth oxide (RO) [(R is lanthanum (La), praseodymium (Pr), neodymium (Nd), samarium (Sm), or yttrium (Y)] into an epitaxial strontium titanate oxide (SrTiO(3)) matrix using pulsed-laser deposition with atomic layer control. We find that structures with La, Pr, and Nd ions result in conducting 2DEGs at the inserted layer, whereas the structures with Sm or Y ions are insulating.

Creation of a two-dimensional electron gas at an oxide interface on silicon.

In recent years, reversible control over metal-insulator transition has been shown, at the nanoscale, in a two-dimensional electron gas (2DEG) formed at the interface between two complex oxides. These materials have thus been suggested as possible platforms for developing ultrahigh-density oxide nanoelectronics. A prerequisite for the development of these new technologies is the integration with existing semiconductor electronics platforms.

Tunneling electroresistance effect in ferroelectric tunnel junctions at the nanoscale.

Using a set of scanning probe microscopy techniques, we demonstrate the reproducible tunneling electroresistance effect on nanometer-thick epitaxial BaTiO(3) single-crystalline thin films on SrRuO(3) bottom electrodes. Correlation between ferroelectric and electronic transport properties is established by direct nanoscale visualization and control of polarization and tunneling current. The obtained results show a change in resistance by about 2 orders of magnitude upon polarization reversal on a lateral scale of 20 nm at room temperature.

Strain-induced polarization rotation in epitaxial (001) BiFeO3 thin films.

Direct measurement of the remanent polarization of high quality (001)-oriented epitaxial BiFeO3 thin films shows a strong strain dependence, even larger than conventional (001)-oriented PbTiO3 films. Thermodynamic analysis reveals that a strain-induced polarization rotation mechanism is responsible for the large change in the out-of-plane polarization of (001) BiFeO3 with biaxial strain while the spontaneous polarization itself remains almost constant.

High-dose methylprednisolone therapy for acute graft-versus-host disease associated with matched unrelated donor bone marrow transplantation.

Acute graft-versus-host disease (aGVHD) is a major barrier to successful bone marrow transplantation (BMT) with matched unrelated donors. Eight of eight recipients of matched unrelated donor BMT developed aGVHD. We used a regimen of high-dose methylprednisolone (5 mg/kg/day for 4 days with responders continuing on treatment, and dose escalation to 10 mg/kg/day for non-responders) as initial therapy of aGVHD.