Oxidative DNA Damage Modulates Trinucleotide Repeat Instability Via DNA Base Excision Repair

Trinucleotide repeat (TNR) expansion is the cause of more than 40 types of human neurodegenerative diseases such as Huntington’s disease. Recent studies have linked TNR expansion with oxidative DNA damage and base excision repair (BER). In this research, we provided the first evidence that oxidative DNA damage can induce CAG repeat deletion/contraction via BER. We found that BER of an oxidized DNA base lesion, 8-oxoguanine in a CAG repeat tract, resulted in the formation of a CTG hairpin at the template strand. DNA polymerase β (pol b) then skipped over the hairpin creating a 5’-flap that was cleaved by flap endonuclease 1 (FEN1) leading to CAG repeat deletion. To further investigate whether BER may help to shorten an expanded TNR tract, we examined BER in a CAG repeat hairpin loop. We found that 8-oxoguanine DNA glycosylase removed the oxidized base located in the loop region of the hairpin leaving an abasic site. Apurinic/apyrimidinic (AP) endonuclease 1 then incised the 5’-end of the abasic site leaving a nick in the loop. This further converted the hairpin into an intermediate with a 3’-flap and a 5’-flap. As a 5’-3’ endonuclease, FEN1 cleaved the 5’-flap, whereas a 3’-5’ endonuclease, Mus81/Eme1, removed the 3’-flap. The coordination between FEN1 and Mus81/Eme1 ultimately resulted in removal of a CAG repeat hairpin attenuating or preventing TNR expansion. To further explore if pol β bypass of an oxidized base lesion, 5’,8-cyclodeoxyadenosine, may affect TNR instability, we examined pol β DNA synthesis in bypassing this base lesion and found that the lesion preferentially induced TNR deletion during BER and Okazaki fragment maturation. The repeat deletion was mediated by the formation of a loop in the template strand induced specifically by the damage. Pol β then skipped over the loop structure creating a 5’-flap that was efficiently removed by FEN1 leading to repeat deletion. Our study demonstrates that pol β-mediated BER plays an important role in mediating TNR deletion and removing a TNR hairpin to prevent TNR expansion. Our research provides a molecular basis for further developing BER as a target for prevention and treatment of neurodegenerative diseases caused by TNR expansion.

Young-Leaf Anthocyanin and Solar Ultraviolet

For six tropical rainforests pecies, young leaves produced on rapidly flushings hoots had markedlyl ower reflectancei n the UV-B region than did mature leaves and contained higher levels of anthocyaninsa nd total phenols. Progressive changes in these characteristicps rovide empirical support for an earlier suggestiont hat anthocyaninsi n flushings hoots of tropicalt rees have adaptive value throught heir ultravioleta bsorption.

In vivo characterization of myocardial tissue post myocardial infarction using combined fluorescence and diffuse reflectance spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region—one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees/severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

Herbivore and nutrient impact on primary producer assemblages in a tropical marine environment

Globally, human populations are increasing and coastal ecosystems are becoming increasingly impacted by anthropogenic stressors. As eutrophication and exploitation of coastal resources increases, primary producer response to these drivers becomes a key indicator of ecosystem stability. Despite the importance of monitoring primary producers such as seagrasses and macroalgae, detailed studies on the response of these benthic habitat components to drivers remain relatively sparse. Utilizing a multi-faceted examination of turtle-seagrass and sea urchin-macroalgae consumer and nutrient dynamics, I elucidate the impact of these drivers in Akumal, Quintana Roo, Mexico. In Yal Ku Lagoon, macroalgae bioindicators signified high nutrient availability, which is important for further studies, but did not consistently follow published trends reflecting decreased δ 15N content with distance from suspected source. In Akumal Bay, eutrophication and grazing by turtles and fishes combine to structure patches within the seagrass beds. Grazed seagrass patches had higher structural complexity and productivity than patches continually grazed by turtles and fishes. Results from this study indicate that patch abandonment may follow giving-up density theory, the first to be recorded in the marine environment. As Diadema antillarum populations recover after their massive mortality thirty years ago, the role these echinoids will have in reducing macroalgae cover and altering ecosystem state remains to be clear. Although Diadema antillarum densities within the coral reef ecosystem were comparable to other regions within the Caribbean, the echinoid population in Akumal Bay was an insufficient driver to prevent dominance of a turf-algal-sediment (TAS) state. After a four year study, declining coral cover coupled with increased algal cover suggests that the TAS-dominated state is likely to persist over time despite echinoid recovery. Studies on macroalgal diversity and nutrients within this same region of echinoids indicated diversity and nutrient content of macroalgae increased, which may further increase the persistence of the algal-dominated state. This study provides valuable insight into the variable effects of herbivores and nutrients on primary producers within a tropical coastal ecosystem. Results from this work challenge many of the currently accepted theories on primary producer response to nutrients and herbivory while providing a framework for further studies into these dynamics.

Web Based Bicycle Trip Planning for Broward County, Florida

To promote the use of bicycle transportation mode in times of increasing urban traffic congestion, Broward County Metropolitan Planning Organization funded the development of a Web-based trip planner for cyclists. This presentation demonstrates the integration of the ArcGIS Server 9.3 environment with the ArcGIS JavaScript Extension for Google Maps API and the Google Local Search Control for Maps API. This allows the use of Google mashup GIS functionality, i.e., Google local search for selection of trip start, trip destination, and intermediate waypoints, and the integration of Google Maps base layers. The ArcGIS Network Analyst extension is used for the route search, where algorithms for fastest, safest, simplest, most scenic, and shortest routes are imbedded. This presentation also describes how attributes of the underlying network sources have been combined to facilitate the search for optimized routes.

Advertising effects on brand search and preference: Assessing the mediational role of *Aad and *Ab

Most advertising research has focussed at examining effects of advertising on attitudinal responses or brand preference and choice. However, in a natural environment, the time period between advertising exposure and purchase decision is filled with prepurchase search. Prepurchase external search refers to information search from sources other than memory, prior to making a purchase decision. Usually consumers access only a small subset of available information and base their choice decisions on it. Prepurchase search therefore acts as a filter and, the final choice depends critically on the small subset of potential inputs the consumer notes in the environment and integrates into the decision. Previous research has identified a variety of factors that affect consumers' prepurchase search behavior. However, there is little understanding of how specific advertisements designed by marketers impact consumers' prepurchase search. A marketer would like consumers to search information that reflects favorably on his/her brand. Hence, s/he would attempt to influence the brands and attributes on which consumers seek information prior to making a choice. The dissertation investigates the process by which a particular marketer's advertising influences consumers' search on available brands, i.e., the marketer's brand and other competing brands. The dissertation considers a situation where exposure to advertising occurs prior to seeking information from any other source. Hence, the impact of advertising on subsequent search behavior is the topic of interest. The dissertation develops a conceptual model of advertising effects on brand search and conducts two experiments to test the tenets of this model. Specifically, the dissertation demonstrates that attitudinal responses generated by advertising mediate advertising effects on search attitudes and behaviors. The dissertation goes on to examine how attitudinal responses generated by advertising and subsequent effects on search alter brand preference and choice. ^

Web Based Bicycle Trip Planning for Broward County, Florida

To promote the use of bicycle transportation mode in times of increasing urban traffic congestion, Broward County Metropolitan Planning Organization funded the development of a Web-based trip planner for cyclists. This presentation demonstrates the integration of the ArcGIS Server 9.3 environment with the ArcGIS JavaScript Extension for Google Maps API and the Google Local Search Control for Maps API. This allows the use of Google mashup GIS functionality, i.e., Google local search for selection of trip start, trip destination, and intermediate waypoints, and the integration of Google Maps base layers. The ArcGIS Network Analyst extension is used for the route search, where algorithms for fastest, safest, simplest, most scenic, and shortest routes are imbedded. This presentation also describes how attributes of the underlying network sources have been combined to facilitate the search for optimized routes.

In Vivo Characterization of Myocardial Tissue Post Myocardial Infarction Using Combined Fluorescence and Diffuse Reflectance Spectroscopy

Accurately assessing the extent of myocardial tissue injury induced by Myocardial infarction (MI) is critical to the planning and optimization of MI patient management. With this in mind, this study investigated the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at the different stages of its development. An animal study was conducted using twenty male Sprague-Dawley rats with MI. In vivo fluorescence spectra at 337 nm excitation and diffuse reflectance between 400 nm and 900 nm were measured from the heart using a portable fiber-optic spectroscopic system. Spectral acquisition was performed on - (1) the normal heart region; (2) the region immediately surrounding the infarct; and (3) the infarcted region - one, two, three and four weeks into MI development. The spectral data were divided into six subgroups according to the histopathological features associated with various degrees / severities of myocardial tissue injury as well as various stages of myocardial tissue remodeling, post infarction. Various data processing and analysis techniques were employed to recognize the representative spectral features corresponding to various histopathological features associated with myocardial infarction. The identified spectral features were utilized in discriminant analysis to further evaluate their effectiveness in classifying tissue injuries induced by MI. In this study, it was observed that MI induced significant alterations (p < 0.05) in the diffuse reflectance spectra, especially between 450 nm and 600 nm, from myocardial tissue within the infarcted and surrounding regions. In addition, MI induced a significant elevation in fluorescence intensities at 400 and 460 nm from the myocardial tissue from the same regions. The extent of these spectral alterations was related to the duration of the infarction. Using the spectral features identified, an effective tissue injury classification algorithm was developed which produced a satisfactory overall classification result (87.8%). The findings of this research support the concept that optical spectroscopy represents a useful tool to non-invasively determine the in vivo pathophysiological features of a myocardial infarct and its surrounding tissue, thereby providing valuable real-time feedback to surgeons during various surgical interventions for MI.

Comparison and Validation of Tropical Rainfall Measuring Mission (TRMM) Rainfall Algorithms in Tropical Cyclones

Tropical Rainfall Measuring Mission (TRMM) rainfall retrieval algorithms are evaluated in tropical cyclones (TCs). Differences between the Precipitation Radar (PR) and TRMM Microwave Imager (TMI) retrievals are found to be related to the storm region (inner core vs. rainbands) and the convective nature of the precipitation as measured by radar reflectivity and ice scattering signature. In landfalling TCs, the algorithms perform differently depending on whether the rainfall is located over ocean, land, or coastal surfaces. Various statistical techniques are applied to quantify these differences and identify the discrepancies in rainfall detection and intensity. Ground validation is accomplished by comparing the landfalling storms over the Southeast US to the NEXRAD Multisensor Precipitation Estimates (MPE) Stage-IV product. Numerous recommendations are given to algorithm users and developers for applying and interpreting these algorithms in areas of heavy and widespread tropical rainfall such as tropical cyclones.