Identification and assessment of potential wind energy project sites in the State of Maryland

Gemstone Team Renewables

Identification and Characterization of New Small Molecule Inhibitors of Picornavirus Replication

The Picornaviridae family consists of positive-strand RNA viruses that are the causative agents of a variety of diseases in humans and animals. Few drugs targeting picornaviruses are available, making the discovery of new antivirals a high priority. Here, we identified and characterized three compounds from a library of kinase inhibitors that block replication of poliovirus, coxsackievirus B3, and encephalomyocarditis virus. The antiviral effect of these compounds is not likely related to their known cellular targets because other inhibitors targeting the same pathways did not inhibit viral replication. Using an in vitro translation-replication system, we showed that these drugs inhibit different stages of the poliovirus life cycle. A4(1) inhibited the formation of a functional replication complex, while E5(1) and E7(2) affected replication after the replication complex had formed. A4(1) demonstrated partial protection from paralysis in a murine model of poliomyelitis. Poliovirus resistant to E7(2) had a single mutation in the 3A protein. This mutation was previously found to confer resistance to enviroxime-like compounds, which target either PI4KIIIβ (major enviroxime-like compounds) or OSBP (minor enviroxime-like compounds), cellular factors involved in lipid metabolism and shown to be important for replication of diverse positive-strand RNA viruses. We classified E7(2) as a minor enviroxime-like compound, because the localization of OSBP changed in the presence of this inhibitor. Interestingly, both E7(2) and major enviroxime-like compound GW5074 interfered with the viral polyprotein processing. Multiple attempts to isolate resistant mutants in the presence of A4(1) or E5(1) were unsuccessful, showing that effective broad-spectrum antivirals could be developed on the basis of these compounds. Studies with these compounds shed light on pathways shared by diverse picornaviruses that could be potential targets for the development of broad-spectrum antiviral drugs.

A NOVEL NON-LETHAL LAPAROSCOPIC APPROACH TO DETECT INTERSEX (TESTICULAR OOCYTES) IN LARGEMOUTH BASS (MICROPTERUS SALMOIDES) AND SMALLMOUTH BASS (MICROPTERUS DOLOMIEU)

The appearance of testicular oocytes (TO) in wild fish populations has received considerable attention in the scientific literature and public media. Current methods to quantify TO are lethal; instead, a non-lethal alternative was examined. Laparoscopic insertion into the genital pore allowed internal visualization of the gonad and detection of TO by collecting five testis biopsies in smallmouth bass Micropterus dolomieu and largemouth bass Micropterus salmoides. Overall, biopsies quantified similar levels of TO detection and severity to conventional transverse sectioning with less than 10% mortality. Suitability of surgical anesthetics, tricaine methanesulfonate and electronarcosis were examined in laboratory and field applications. Electronarcosis had the added benefit of rapid sex identification and immediate release of female fish with minimal trauma, representing significant benefits when sampling small or compromised populations. Laparoscopy may be useful for monitoring the prevalence and severity of TO in these fish species when lethal sampling is not a desired outcome.