Genetic Mechanisms Responsible for Dietary Restriction Dependent Lifespan Extension in Drosophila Melanogaster: A Role for Muscle Tissue

Dietary Restriction (DR) is a robust intervention that is known to extend lifespan and increase spontaneous activity in multiple species. Whether activity increase plays a causal role in mediating the health protective benefits of DR remains unknown. To investigate this relationship, nutritional manipulations and laboratory selection for lifespan were simultaneously applied. Three physiological outputs were used for the screening and characterization of genes that may mediate the effects of DR: starvation resistance, spontaneous activity levels, and lifespan. The physiologic changes that occur are partially mediated by the nutrient sensing TOR pathway and its downstream signaling components, specifically the translational repressor, eukaryotic initiation factor eIF4E binding protein (4E-BP). Overexpression of constitutively active d4E-BP in the muscle tissue of Drosophila melanogaster led to starvation resistance and increased activity in flies fed a nutrient rich diet. However, the associated lifespan extension effect observed in previous studies was not reproduced. This may be due to the use of a different laboratory strain of d4E-BP, of which there are several. Three downstream targets of 4E-BP were identified from screening: Fumble, Nemo, and Nedd2-like Caspase. Both Fumble and Nemo extend lifespan upon DR when inhibited in the muscle tissue. While these candidate genes hold promise for future studies in healthy aging, sources of variation in results must be controlled. In order to truly understand the influence that a specific mutant gene has on lifespan, results need to be clearly interpretable, robust and repeatable. Only then will it be possible to start making conjectures about their relevance to human aging

Fate of organic compounds associated with extractable and bound phases of estuarine sediments deposited under varying depositional regimes

Surficial sediments and sediment cores were collected from two distinct depositional regimes of the York River subestuary of Chesapeake Bay to document seasonal inputs, spatial variability, and longer-term (\u3e40 years) fate of total organic carbon (TOC), lipid biomarker compounds and polycyclic aromatic hydrocarbons (PAHs). These regimes included biological mixing in the lower York and episodic mixing at the mid river site. Compounds were selected to represent a range of chemical reactivities, biological and anthropogenic sources, and modes of entry to the environment. The depositional environments were characterized with a suite of analytical tools: x-radiographs, Eh, 210Pb and 137Cs, total organic carbon, total nitrogen, and their stable isotopes. Each compound class was quantified in extractable and bound phases. Episodic mixing at the mid-river site resulted in stronger oxidizing conditions that promoted enhanced degradation of labile organic matter (e.g. diatoms) vs. refractory material (e.g. higher plants) in extractable sedimentary phases from sediments \u3c5 yrs old. However, while apparent rate constants for bulk organic matter and total lipid were higher in older sediments (\u3c40 years) under physically mixed conditions, degradation rates of fatty acid and sterol biomarkers were similar at both study sites. PAHs and lipid biomarkers isolated from bound phases were better preserved over time than corresponding extractable compounds. However, stabilization in the bound phase was not the same among compound classes. Differences in compound class fate were a function of inherent compound class reactivity (fatty acids \u3e sterols and PAHs) rather than source or depositional regime. While compounds in bound phases may be formed over time during organic matter diagenesis, organic compounds did not increase in bound residues over time regardless of depositional regime, suggesting that bound phase compounds are formed within the source organism or very rapidly upon cell death and/or deposition to the sediments. The fate of organic carbon in coastal sediments is dependent upon the source and reactivity of organic carbon, the depositional regime, and its association with the underlying sediment/macromolecular matrix. Models of coastal carbon dynamics that consider these parameters and how they change will yield more accurate forecasts of coastal biogeochemical cycling

Activity of Pterostilbene Metabolites against Liver Steatosis in Cultured Hepatocytes

Pterostilbene is a dimethyl ether derivative of resveratrol, less metabolized than its analogue, due to the substitution of two hydroxyl groups with methoxyl groups. Nevertheless, the amounts of pterostilbene phase II metabolites found in plasma and tissues are higher than those of the parent compound. The first aim of this study was to assess whether pterostilbene-4′-O-glucuronide (PT-G) and pterostilbene-4′-O-sulfate (PT-S) were able to prevent triglyceride accumulation in AML12 (alpha mouse liver 12) hepatocytes. This being the case, we aimed to analyze the mechanisms involved in their effects. For this purpose, an in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10 or 25 µM of pterostilbene, pterostilbene-4′-O-glucuronide or pterostilbene-4′-O-sulfate for 18 h. Triglycerides and cell viability were assessed by a commercial kit and crystal violet assay, respectively. Protein expression of enzymes and transporters involved in triglyceride metabolism was analyzed by immunoblot. The results showed for the first time the anti-steatotic effect of pterostilbene metabolites and thus, that they contribute to the preventive effect induced by pterostilbene on steatosis in in vivo models. This anti-steatotic effect is mainly due to the inhibition of de novo lipogenesis.This research was funded by Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (grant number AGL-2015-65719-R MINECO/FEDER, UE), Instituto de Salud Carlos III CIBERobn (grant number CB12/03/30007) and University of the Basque Country (grant number GIU 18/173)

Supplemental Data: Effects of physical mixing on the attenuation of polycyclic aromatic hydrocarbons in estuarine sediments.

To examine the role of physical disturbance on the long-term preservation of polycyclic aromatic hydrocarbons (PAHs) in sediments, cores were collected from two sites removed from point sources of PAHs and representing contrasting seabed mixing regimes. Although SPAH concentrations in sediments over the past 50 years were not significantly different between the two sites, several PAH isomer ratios were significantly different (

Inhaled Nitric Oxide Therapy for Pulmonary Disorders of the Term and Preterm Infant

The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the two randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure

Examining Overrepresentation in Special Education amongst African Americans Diagnosed with Emotional Disturbance in the State of Pennsylvania

This study examines the disproportionality in special education, regarding African American students being overrepresented, specifically under the disability category of Emotional Disturbance (ED) within the state of Pennsylvania. Demographic information was collected with the use of secondary data provided by the Pennsylvania Department of Education, using 648 educational programs across 29 intermediate units. Data were analyzed with statistical representation of percentages as related to risk composition and the E-Formula. The results yielded an average risk of African American students being two times more likely to be diagnosed with ED than their White peers. Additional results from the calculation of the E-Formula showed an overrepresentation of African American students within the state of Pennsylvania under the disability category of ED between the schoolyears of 2011-2021. The results of the study can be used to aid in the programming for future teacher preparation program, training for current teachers working in the field, and to initiate change amongst legislation regarding determining appropriate thresholds for significant disproportionality

Offshore Wind Energy's Role in the United States' Energy Transition

As the human population grows, the need for alternative and clean forms of energy is greater. The installation of offshore wind energy has been on the rise over the past decade, however the fossil fuel energy generation sectors, such as coal and natural gas, are still major players in the energy supply markets. Wind turbines emit sound and electromagnetic energy, whereas fossil fuel burning activities discharge large quantities of carbon dioxide into the atmosphere, which is absorbed by the ocean. Many species are sensitive to auditory and electromagnetic disturbances caused by the different stages of offshore wind development, but many of the effects caused by the wind turbines appear to be less impactful and destructive compared to the formation of carbonic acid and rising ocean acidity levels. Marine species and ecosystems can display unique biological responses to different impacts. The goal of this research is three-fold: To inform the public of the environmental issues surrounding fossil fuel energy generation; to describe what is required to phase fossil fuels out, and to summarize the status of offshore wind energy as a resource to offset fossil fuels and its potential impacts