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Pigmented Villonodular Synovitis: A Dissection & Photographical Documentation

By: Scott Campit and John Yassa

Physiology

Faculty Advisors: Ryan Marder and Gloria Nusse

Pigmented Villonodular Synovitis (PVNS) is a rare overgrowth of the synovium, the connective tissue that lines our joints. While PVNS has been cited in case studies regarding patients that have been previously diagnosed with arthritis, PVNS has not been cited in cadaveric studies that we know of. Studying diseases in cadavers provides a powerful teaching tool towards future healthcare providers and scientists in studying the relationship between structure and function in the human body. We hypothesize that higher resolution photographs of PVNS will be able to materialize the images seen in MRI, CT, and other scans. Photos of the synovial outgrowth on the knee were taken using a Reichert dissecting microscope, as well as a Nikon D600 with a Nikon Micro-NIKKOR 105mm Lens. While previous photos of a dissected synovial joint had not been documented in a cadaveric specimens beforehand; the ones developed from this cadaver, were able to give insight on the physical manifestations of PVNS as well as show higher definition of the characteristics of the disease, particularly its pigmented nodules. Different photographs display the progression of the disease in particular joints with the development of synovial pigmentation to nodule formation. By studying PVNS in the cadaver, we can present the tumor in a new light for those studying anatomy and physiology, as well as provide excellent models for analyzing arthritic diseases.

153 UL2 DISPLAY ONLY

Skin Grafts: Skin Surgery with a Modern Twist

By: Nadia Nguyen

Physiology

Faculty Advisor: Gloria Nusse

This project was orginally helping Professor Nusse recreate the integumentary lab for the anatomy course (biol 328). We discovered that the one of the anatomy cadavers had skin grafts and thought it would be a good idea to display it as a project. I would collectively research the history of what it is, the biological mechanisms, and how it relates to how I'm recreating the integumentary lab.

154 UP1

Synthesis, Characterization, & Biochemical Assay of Heteroaryl-aryl Thiazole Inhibitors of UT-A

By: Anthony J. Burt

Chemistry

Faculty Advisor: Dr. Marc Anderson

Urea transport (UT) proteins present an untapped therapeutic target for diuretic type drugs. UT-A1 found in the kidney-medullary-tubule collecting duct is of particular interest with in vivo studies with rats showing an increased production of urine with increased osmolality2. Our lab set out to diversify the known low micro molar potent UTA1inh-E02 scaffold1 in two phases. Phase 1 involved diversification of the heteroaryl group as well as contrasting effects of para vs meta acetamids. Biological screening results for all compounds yielded results no better than the lead compound. Leading to phase 2 where the lab set out to test whether substitution of the indole will lead to nano molar potency. In the process, synthetic techniques were developed for the conversion of carboxylic acids to nitriles, nitriles to thioamides, and subsequent thiazole cyclization. Compounds were characterized with LCMS and 1 and 2D NMR techniques.

155 UP1

An Efficient Domino Amination-Oxidation Reaction for the Copper-Catalyzed Synthesis of Anilines

By: Christopher Thomas and Marvin Wu

Chemistry

Faculty Advisor: Dr. Kelvin L. Billingsley

An Efficient Domino Amination-Oxidation Reaction for the Copper-Catalyzed Synthesis of Anilines / / Christopher Thomas,+ Marvin Wu,+ and Kelvin L. Billingsley* / / *Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA 94132 / +These authors contributed equally to this work. / / Metal-catalyzed processes for carbon-nitrogen bond formation have become fundamental to the drug discovery industry. Over 90% of the current top-selling brand name pharmaceuticals contain at least one nitrogen atom in their molecular structure, and advancements in palladium- and copper-catalyzed carbon-nitrogen bond synthesis have substantially impacted the design and identification of these drug candidates. For example, aryl amines (anilines) are ubiquitous structural motifs in pharmaceutically-interesting compounds, but classical methods are generally not amenable for the synthesis of a wide range of anilines. Copper catalysis obviates these issues by providing an operationally simple method for reacting an aryl electrophile (e.g., aryl halide) with an alkyl or aryl amine to form the desired carbon-nitrogen bond. Despite these advancements, the synthesis of monoarylated anilines by catalytic methods remains challenging as often di- and triarylated anilines are observed as undesired byproducts. To address these issues, we developed a domino copper-catalyzed process in which aryl iodides and bromides can be efficiently transformed into the corresponding monoarylated anilines. This method employed a non-traditional nitrogen source, valine, to promote carbon-nitrogen bond formation and importantly prevented the formation of di- and triarylated aniline byproducts. Based upon mechanistic experiments, we have proposed that the reaction proceeds in two distinct steps: (1) carbon-nitrogen bond formation and (2) oxidation of the amine to an imine. Hydrolysis of the imine post-reaction afforded the corresponding monoarylated aniline. This novel copper-catalyzed method allowed for the synthesis of arylamines in modest to excellent yields and represents a mechanistically innovative process for selective carbon-nitrogen bond formation with aryl halides. /

156 UP1

Investigation of the Secondary Metabolites Produced by the Marine Sediment-Derived Streptomyces sp. CP53-67

By: Lisa Liu

Chemistry

Faculty Advisor: Dr. Taro Amagata

Our research group focuses on discovering novel cytotoxic compounds with excellent solid tumor selectivity produced by marine sediment-derived actinomycetes. We recently tested a mini-library containing 60 different organic extracts created from strains of actinomycetes against a series of cancer cell lines at Josephine Ford Cancer Center. In the library, four strains showed significant selective cytotoxicity against the cancer cell lines. One of the active strains, Streptomyces sp. CP53-67, showed potent and significant selective activity against the ovarian cancer cell line (OVC-5) was selected for further study. Media optimization was performed using four different media condition to improve the productivity of the strain CP53-67. The results suggested that addition of glucose increased the amount extract by ten fold. In addition, changing the carbon source from soluble starch to glycerol considerably alternated the chemical profile of this strain. The major compound in the extract obtained from the culture medium with glycerol was identified as a derivative of abierixin, the polyether class of compound, based on the NMR and MS analysis. The cytotoxic effects of the extract, media optimization study, and structure analysis of the major compound will be presented.

157 UP1

Unique Roles of Divalent Metal Ions in Tuning the Mechanism of Pyridine Nucleotide Exchange in a Phenylacetaldehyde Dehydrogenase

By: Azeb Teklezgi, Elizabeth Abuhay, Olga Byakina, and Lourin Alayoub

Biochemistry

Faculty Advisor: Dr. George Gassner

Phenylacetaldehyde dehydrogenase oxidizes phenylacetaldehyde to phenylacetic acid in the last step of the styrene catabolic and detoxification pathway of P. putida (S12). This enzyme assembles as a homotetramer with four identical aldehyde and pyridine nucleotide binding sites. It follows a sequential reaction mechanism. Oxidized pyridine nucleotide NAD+ binds as the first substrate triggering the enzyme to bind the second substrate, phenylacetaldehhyde, which reacts with the active site cysteine to form a thiohemiacetal intermediate. Hydride transfer from the thioacetal to NAD+ results in enzyme-bound reduced pyridine nucleotide (NADH) and phenylacetate-thioester intermediate. In the last steps of the reaction, the thioester undergoes hydrolysis and the enzyme sequentially releases phenylacetic acid and NADH. / The styrene catabolic pathway begins with the consumption of NADH by the styrene monooxygenase reductase (SMOB) component of styrene monoxygenase, which was previously found to interact with its partner, styrene monooxygenase in an FAD exchange reaction. The NAD+ produced in the SMOB-catalyzed FAD-reduction step is efficiently recycled by the aldehyde of PADH in a step that may similarly involve protein-protein interactions in pyridine nucleotide exchange. In this work we have used structural bioinformatics tools to evaluate candidate structures of potential catalytic complexes formed. / Divalent metal ions play a central role in catalysis by PADH. Crystallographic analysis the closely related human mitochondrial aldehyde dehydrogenase suggest two modes of metal ion binding and we expect these to influence the dynamics of the pyridine nucleotide exchange and recycling in the styrene pathway. Stopped-flow kinetic studies of the metal ion binding specificity will be reported in view of their structural configuration, and the hypothesized function of these metal-binding sites in directing the pyridine nucleotide recycling reactions will be discussed.

158 UP1

Evaluating the Reaction of NSMOA with Acetylene Substrates

By: Chris Cabeza and Jose Diaz

Biochemistry

Faculty Advisor: Dr. George Gassner

The styrene catabolic and detoxification pathway of Pseudamonas putida S12 begins with styrene monooxygenase (SMO) that contains a two-component flavoenzyme with a NADH-specific flavin reductase, SMOB, and FAD-specific styrene epoxidase, SMOA. In catalysis SMOB catalyzes the reduction and transfer of FAD to SMOA. Reduced FAD reacts with oxygen in the active site of SMOA to generate an electrophilic FAD C-(4a) hydroperoxide that reacts enantioselectively with styrene to yield (S)-styrene oxide and a highly fluorescent enzyme-bound C-(4a) hydroxyFAD intermediate. Elimination of water from this intermediate regenerates the oxidized FAD. In the present work, we investigate the reactivity of SMO with alternate acetylene substrates as a potential enzyme catalyzed route to the synthesis of ketenes. Kinetic studies of epoxidation reaction of wild type SMOA with styrene and oxygen atom transfer of phenylacetylene and acetylene were conducted on stopped-flow instrument detecting fluorescence, the formation of flavin hydroxide. FAD was recovered from the enzyme after stopped-flow that was evaluated by diode array-monitored high-pressure liquid chromotography (HPLC). These studies suggest the acetylene reaction possibly modifies the flavin. In addition to a peak corresponding to oxidized FAD, a new later eluting peak with a UV-absorbance maximum of 360 nm was detected. The structure of the modified flavin will be evaluated by mass spectrometry. Kinetic studies showed the oxygen atom transfer rate constants of phenylacetylene and acetylene to be 2.68 s-1 and 1 s-1 with wild type SMOA, which are significantly slower than styrene. We further studied kinetics with mutant SMOA V303I and acetylene giving a faster oxygen atom transfer rate of 2.7 s-1 than wild type. This suggested mutations on SMOA active site could provide an alternative reaction with acetylene-like substrates.

159 UP1

Synthesis and Characterization of Titanosilicate (TS-1)

By: Christopher Stables and Yen Tran

Biochemistry

Faculty Advisor: Dr. Andrew Ichimura

Titanosilicate-1 (TS-1) is a micro-porous, silicon-based zeolite with ~1-2% of titanium substituted for Si within the framework. TS-1 plays an important role in aromatic hydroxylation, cyclohexanone oxime synthesis, and epoxidation. TS-1 also has a green chemistry component through its unique reductive photocatalytic behavior in the reduction of CO2 and H2O into fuels such as methanol and other light hydrocarbons. The synthesis of TS-1 followed literature procedures. The crystalline materials was prepared from sol gels composed of tetraethylorthosilicate (TEOS), tetrapropylammoniumhydroxide (TPA-OH), titanium (IV) butoxide (TBOT) or titanium isoproxide (TTIP), with and without ammonium carbonate ((NH4)2CO3). Two synthesis methods were attempted. First, TPA-OH (25 wt% in H2O) was mixed with the titanium source TBOT and stirred until the solution was homogeneous. Next, TEOS was added and hydrolyzed. The pH was adjusted by the addition of (NH4)2CO3 (pH=11.05). The second method followed previously stated techniques, replacing the Ti source with titanium isoproxide (TTIP) with the exclusion of (NH4)2CO3. Both methods was then placed into the Teflon liner of a Parr reactor, sealed, and then placed in an oven. The first method was held a temperature of 180 °C for 72 hours and the second method was placed into the oven at 150 °C for 5 hours. The TS-1 powders were characterized by X-ray diffraction (XRD), UV-Vis reflectance spectroscopy, scanning electron microscopy (SEM), 29Si magic angle spinning nuclear magnetic resonance (MAS-NMR) and a Fourier transform infrared (FTIR) spectroscopy. The resulting material was crystalline and contained titanium as shown by XRD, diffuse reflectance UV-vis and FTIR spectra. Two peaks in the UV-vis spectrum indicate octahedral and tetrahedral complexes of Ti. A major goal of this work is to eliminate the octahedral extraframework Ti(IV), which was found to hinder the catalytic properties of TS-1. Preliminary results of the photoreduction of CO2 and H2O to methanol and ethanol will be reported.

160 UP1

SMOA interactions with arylallenes and fulvens

By: Gabriel Cabrera

Biochemistry

Faculty Advisor: Dr. George Gassner

Styrene monooxygenase (SMO) is two-component flavoprotein composed of an FAD-specific epoxidase (SMOA) and NADH-specific flavin reductase (SMOB). SMO catalyzes the enantioselective epoxidation styrene and a broad range of styrene analogs to yield corresponding (S)-styrene oxides. Here we evaluate the reactivity of SMO with arylallenes and fulvenes, which have previously defined activity with singlet oxygen. Our objective in this and future studies is to establish the mechanism of the reaction of NSMOA with these substrate analogs and to characterize the nature of the products generated in these transformations. The single-turnover kinetics of the reaction NSMOA, the N-terminally histidine-tagged epoxidase (NSMOA) with oxygen and substrate analogs were characterized by stopped-flow fluorescence spectroscopy. Arylallene and a-methylarylallene were observed to react with rate constants of (8.6 s-1 and 3.8 s-1, respectively. 6-dimethyl fulvene was found to react at 40.2 s-1 compared with styrene (51.4 s-1) . In order to produce sufficient quantities of reaction products for structural identification by NMR, a steady-state product generating system was constructed by coupling the epoxidase and aldehyde dehydrogenase activities of the styrene pathway. In this system acetaldehyde was used as a source of electrons for the synthesis of NADH by the aldehyde dehydrogenase NPADH. Our results indicate that the expoxidation of either allene bond results in oxyallyl intermediate leading to carboxyl formation in the allene position and the formation of formaldehyde. For 6-dimethylfulvene our resylts indicate the formation of 2-(propan-2-ylidene)-6-oxabicyclo[3.1.0]hexan-3-one.

161 UP1

Kinetic characterization of a predicted phosphinothricin acetyltransferase (SMc03840) from the plant symbiont Sinorhizobium meliloti

By: Joseph Dang and Sarah Lewis

Biochemistry

Faculty Advisor: Dr. Misty Kuhn

Gcn5-related N-acetyltransferases (GNATs) are enzymes that belong to a diverse superfamily, which use acetyl coenzyme A to acetylate primary amino groups on a variety of molecules. One type of GNAT that belongs to this superfamily is phosphinothricin acetyltransferase (PAT). Bacterial PATs acetylate the natural herbicide phosphinothricin (glufosinate), which is a potent inhibitor of glutamine synthetase. Typically, this enzyme has been exploited for use in herbicide resistance in plants, but recently its native function has been brought into question. Many bacterial genes have been annotated as PATs; however, some are unable to acetylate phosphinothricin and modify other metabolites instead. To improve the functional annotation of these genes, we are investigating the potential native function of a PAT from the plant symbiont Sinorhizobium meliloti. We used a broad-substrate screening assay to identify possible substrates for this PAT and determined the kinetic properties of the enzyme to understand its substrate specificity. Our kinetic analysis showed that compounds structurally similar to phosphinothricin, such as L-methionoine sulfoximine, L-methionine sulfone and L-methionine sulfoxide, are substrates for PAT. Based on these results, we propose that PATs are promiscuous enzymes that have additional/alternative functions to phosphinothricin acetylation.

162 UP1

Oxidation of Cr(III) to Cr(VI) by Manganese Oxide Soil Minerals

By: Leslie Galvez and Sukhdeep Khatra

Biochemistry

Faculty Advisor: Dr. Bruce Manning

High chromium (Cr) concentrations can threaten the environment via contaminated ground, surface, and industrial waste waters. The trivalent form Cr(III) occurs naturally and is the predominant form in soil and geologic materials whereas the hexavalent form Cr(VI) is produced by various industrial processes. The Cr(VI) species is highly toxic causing major health problems such as lung cancer and can end up in the brownfield land of abandoned industrial sites. This study was an investigation of the oxidation of Cr(III) to Cr(VI) by manganese oxide (MnO2), a natural soil mineral with a poorly crystalline structure capable of oxidizing dissolved ions. Several experiments were performed including batch reactions at varying Cr(III) concentrations and pH. Total Cr and Mn were measured by microwave plasma-atomic emission spectrometry (MP-AES) and Cr(III)/Cr(VI) speciation was performed by UV-Vis absorption spectroscopy. The results of this study showed that oxidation of Cr(III) to Cr(VI) is coupled with the reduction of solid MnO2 to dissolved Mn(II). Natural MnO2 will oxidize Cr(III) to Cr(VI) and thus a knowledge of soil mineralogy will help determine the mobility and bioavailability of Cr in the environment.

163 UP1

Thioester Hydrolysis and Transthioesterification Reactions of N-Terminally Histidine-Tagged Phenylacetaldehyde Dehydrogenase (NPADH)

By: Tatiana Ouabo and Iman Tassavor

Biochemistry

Faculty Advisor: Dr. George Gassner

Phenylacetaldehyde dehydrogenase catalyzes the NAD+-dependent oxidation of phenylacetaldehyde to phenylacetic acid in the last step of the styrene catabolic and detoxification pathway of Pseudomonas putida (S12). Studies of NPADH indicate a sequential reaction mechanism with NAD+ as the leading substrate. The binding of the second substrate, phenylacetaldehyde (PAL), triggers the enzyme to initiate covalent catalysis through an active site cysteine that attacks the aldehyde to form a tetrahedral thiohemiacetal intermediate. Hydride transfer from the thiohemiacetal to NAD+ yields enzyme-bound, reduced pyridine nucleotide, NADH, and phenylacetate covalently joined with the active site cysteine through a thioester bond. In the present work we evaluate the reactivity of the thioester intermediate with water and thiol substrates. The thioester intermediate is synthesized by rapidly mixing NPADH with the nitrophenol ester of phenylacetic acid. The synthesis of this intermediate is coupled to the pre-steady state release of the strongly absorbant nitrophenylate anion. Subsequently, the rate limiting elimination of phenylacetate is monitored in reactions with different acceptor molecules. We find a limiting rate constant of 2.78s-1 corresponding to the thioester hydrolysis at pH 7. We found the product elimination reaction to be greatly accelerated when either dithiothreitol (DTT) or cysteine is included as a substrate. These reactions follow saturation kinetics with kcat/Km = 1,892 µM-1s-1 for DTT and 645 µM-1s-1 for cysteine. This work demonstrates an alternate route for the breakdown of the thioester product intermediates that may be of physiological relevance to the cell and of biotechnological value for the synthesis of thiol esters of glutathione, lipoic acid, or Coenzyme A.

164 UP1

Chemical investigation of the saltwater obligate Streptomyces sp.CP28-49

By: Tiffany Cinev

Biochemistry

Faculty Advisor: Dr. Taro Amagata

Recent studies have demonstrated that secondary metabolites obtained from marine invertebrates have biological activity against cancer cell. However, the chemical structure of marine obligate secondary metabolites is poorly studied. The purpose of this study is to investigate the structure of secondary metabolites produced by saltwater obligate actinomycetes. The organic extract of the saltwater obligate Streptomyces sp. CP28-49, cultured in 9L of liquid media, showed a unique chemical profile in RP- HPLC analysis. The supernatant underwent a series of methanol and ethyl acetate extractions and evaporated under reduced pressure to give the organic extract. The organic extract was purified using RP- HPLC and subjected to 1H-NMR and mass spectroscopy. Preliminary MS results showed that the compound had a MW=412kDa.

165 UP1

Statistical Evaluation of High-resolution WRF-ARW Model Temperature Forecast Near San Francisco Peninsula

By: Yilin Lu

Atmospheric and Oceanic Sciences - Meteorology

Faculty Advisors: Dr. Dave Dempsey, Dr. John Monteverdi, Dr. Leonard Sklar, and Dr. Alexander Stine

The Advanced Research version of the Weather Research & Forecasting (WRF-ARW) model can make weather forecasts on bounded regions in space (domains) with high spatial and temporal resolution. This project will use station observation to evaluate accuracy of the model forecasts of temperature within the San Francisco Bay area domain since middle August last year, in order to see the range of differences between the forecasts and the observation.

166 UP1

Gormandize - A Data Analysis of Restaurants

By: Brendan Luna, Michael Smith, and Kevin Soncuya

Computer Science

Faculty Advisor: Dr. William Tsun-yuk Hsu

Gormandize is an interactive and visual display of restaurant and business search results. Using the Yelp and Foursquare APIs, Gormandize pulls and displays location result markers onto a Leaflet map and provides comparative result data in JavaScript graphs.

167 UP1

Chillspot

By: Jordan Schwichtenberg

Computer Science

Faculty Advisor: Dr. William Tsun-yuk Hsu

Chillspot is an Android app with a web server back end and its purpose is to bring users together for activities— which may be sports, card games, or general meet-ups. Instead of planning events, Chillspot’s purpose is to find events happening right now near you. Events only appear if they are currently taking place, and events only appear to users if they are nearby.

168 UP1

Beat

By: Lowell Milliken and Stanley Seeto

Computer Science

Faculty Advisor: Dr. William Tsun-yuk Hsu

Beat is a Processing application that allows users to generate and customize a beat map based upon a single track from a midi file and engage themselves on their generated beat map. Beat is inspired by other rhythm games such as OSU, Patapon, and DJ Max. Our application is closer to DJ Max, than the other examples. Rhythm games are action based video games that require the user to be able to sync himself with the rhythm of a song or the pacing of events. Beat maps are a mapping of rhythm from a song. In most cases, a beat map is generated manually to provide aesthetically pleasing appearance. Our application generates a beat map based on the musical notes within a track in a midi file. Each musical note is mapped to a specific hotkey, which the user needs to press. During the generation of a beat map, our application provides the user with multiple customization options such as a change of display and the size and shape of the note events.