acase@tulane.edu

Germanium nanoparticles (Ge NPs) may be fascinating for their electronic and optoelectronic properties, as the band gap of Ge NPs can be tuned from the infrared into the visible range of solar spectru. Further functionalization of those nanoparticles may potentially lead to numerous applications ranging from surface attachment, bioimaging, drug delivery and nanoparticles based devices. Blue luminescent germanium nanoparticles were synthesized from a novel top-down mechanochemical process using high energy ball milling (HEBM) of bulk germanium. Various reactive organic molecules (such as, alkynes, nitriles, azides) were used in this process to react with fresh surface and passivate the surface through Ge-C or Ge-N bond. Various purification process, such as gel permeation chromatography (GPC), Soxhlet dailysis etc. were introduced to purify nanoparticles from molecular impurities. A size separation technique was developed using GPC. The size separated Ge NPs were characterize by TEM, small angle X-ray scattering (SAXS), UV-vis absorption and photoluminescence (PL) emission spectroscopy to investigate their size selective properties. Germanium nanoparticles with alkyne termini group were prepared by HEBM of germanium with a mixture of n-alkynes and α, ω-diynes. Additional functionalization of those nanoparticles was achieved by copper(I) catalyzed azide-alkyne ""click"" reaction. A variety of organic and organometallic azides including biologically important glucals have been reacted in this manner resulting in nanopartilces adorned with ferrocenyl, trimethylsilyl, and glucal groups. Additional functionalization of those nanoparticles was achieved by reactions with various azides via a Cu(I) catalyzed azide-alkyne ""click"" reaction. Various azides, including PEG derivatives and cylcodextrin moiety, were grafted to the initially formed surface. Globular nanoparticle arrays were formed through interparticle linking via ""click"" chemistry or ""host-guest"" chemistry. Copper(I) catalyzed ""click"" chemistry also can be explored with azido-terminated Ge NPs which were synthesized by azidation of chloro-terminated Ge NPs. Water soluble PEGylated Ge NPs were synthesized by ""click"" reaction for biological application. PEGylated Ge NP clusters were prepared using α, ω-bis alkyno or bis-azido polyethylene glycol (PEG) derivatives by copper catalyzed ""click"" reaction via inter-particle linking. These nanoparticles were further functionalized by azido β-cyclodextrin (β-CD) and azido adamantane via alkyne-azide “click” reactions. Nanoparticle clusters were made from the functionalized Ge NPs by “host-guest” chemistry of β-CD functionalized Ge NPs either with adamantane functionalized Ge NPs or fullerene, C60. / acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

Biological invasions are a global threat to aquatic biodiversity. Of particular concern are invasive freshwater fishes because they have high establishment rates, and introductions can result in the displacement and extirpation of native species through a range of processes including competition and hybridization. Though it is well known that invasive freshwater fishes commonly spread following introduction events, little is known about how fast and far they may move. Additionally, observations of hybridization involving invasive stream fishes have been linked to elevated turbidity; however, the extent to which impaired water clarity influences reproductive isolation among invasive and native species remains poorly understood. To better understand how invasive freshwater fishes disperse, and how turbidity affects reproductive isolation between native and non-native species, I carried out a series of three related studies. First, I evaluated genetic variation across the native and invasive ranges of red shiner (Cyprinella lutrensis), throughout the United States. Second, I characterized genetic variation and clinal stability across a hybrid swarm involving native blacktail shiner (Cyprinella venusta stigmatura) and invasive red shiner in the Upper Coosa River Basin (UCRB), USA. Third, I examined whether turbidity influences pre-mating social interactions between invasive red shiner and native blacktail shiner. MtDNA haplotypes from native range populations of red shiner form four divergent lineages and suggest that introduced populations in the western and eastern US originate from dissimilar genetic lineages. I also recovered a previously undescribed lineage of Cyprinella that has been cryptically introduced into the western US. Examination of the hybrid swarm in the UCRB revealed that the proportion of hybrids increased between 2005 and 2011, and that the hybrid swarm is continuing to expand both upstream and downstream. Under turbid conditions, I found that pre-mating social interactions increased, and that native blacktail shiner females are especially likely to interact with invasive red shiner males. Localized control or removal may be effective in managing non-native red shiner; further monitoring, however, is needed to help identify additional factors contributing to hybrid swarm movement. Furthermore, integrating knowledge of species behavior into management planning could help deter the further establishment and spread of invasive red shiner. / acase@tulane.edu

acase@tulane.edu

The oncogenic isoform of HER2, HER2Δ16, is expressed with HER2 in nearly 50% of HER2 positive breast tumors where HER2Δ16 drives metastasis and resistance to multiple therapeutic interventions including tamoxifen and trastuzumab. The research carried out in this dissertation investigated the molecular mechanisms underlying HER2Δ16 activity contributing to primary trastuzumab resistance. In recent years microRNAs have been shown to influence multiple aspects of tumorigenesis and tumor cell response to therapy. Accordingly, the HER2Δ16 oncogene alters microRNA expression to promote endocrine resistance. With the goal of identifying microRNA suppressors of HER2Δ16 oncogenic activity, we investigated the contribution of altered microRNA expression to HER2Δ16-mediated tumorigenesis and trastuzumab resistance. Using a gene array strategy to compare the microRNA expression profiles of MCF-7 to MCF-7/HER2Δ16 cells, we found that HER2Δ16 suppresses expression of the miR-7 tumor suppressor. Reestablishing miR-7 expression significantly inhibits HER2Δ16-mediated tumor cell proliferation and migration, as well as sensitizes HER2Δ16-expressing cells to trastuzumab treatment. We propose that miR-7 regulated pathways, including EGFR and Src kinase, represent targets for the therapeutic intervention of refractory and metastatic HER2Δ16-driven breast cancer. Research in the past decade in HER2-positive breast cancer has focused on elucidating the molecular basis of primary and acquired trastuzumab resistance. Our laboratory has shown that critical and clinically important resistance pathways may be deregulated and only revealed during drug treatment. To identify potential resistance pathways deregulated during trastuzumab treatment, we used a phosphoproteomic approach to profile a subset of phosphorylation events after HER2Δ16-overexpressing cells were treated with trastuzumab. We discovered trastuzumab treatment significantly induced activation of ribosomal p70S6 kinase 1 (p70S6K) and aberrant signaling activity of this kinase is implicated in several disease models due to its role in regulating protein synthesis, cell proliferation and survival. Our data indicates that trastuzumab activates p70S6K to promote prosurvival signaling in breast cancer cells with inherent resistance. We propose that p70S6K can be evaluated in HER2-positive breast cancer patients undergoing trastuzumab treatment as a biomarker to predict therapeutic response. Overall, our research establishes that HER2Δ16 expression is an important genetic event in HER2 tumorigenesis and drives trastuzumab refractory breast cancer. / acase@tulane.edu

The purpose of this study is to elucidate the historical processes that have impacted the fishes of the Fouta Djallon highlands and surrounding areas. This mountainous region in Guinea, West Africa, lies on the northern edge of the Guinean Range. This geologic formation, of Jurassic origins, has long reported to serve as a barrier to dispersal in the region. These highlands currently separate two ichthyo-provinces in the area. The upper-Guinean province encompasses rivers on the Western slopes of the range that flow directly into the Atlantic Ocean. The Nilo-Sudan province is comprised of the rivers and streams on the Eastern slopes of the Guinean Range. These rivers flow west or north through the Sahel and eventually back to the Atlantic Ocean. While these highlands clearly serve as a barrier to dispersal for most fish taxa, some taxa are reported to occur on both sides of the Fouta Djallon. This study investigates three groups of these “amphi-Guinean†taxa to determine if the same taxa are present within both provinces and what processes would have allowed for this dispersal to take place. In addition to the biogeographical questions addressed within the Fouta Djallon region, specimens from the surrounding areas are included to further understand the historical biogeography of these groups in West Africa. This study revealed the presence of numerous undescribed species within the Amphilius, Chiloglanis, and ‘Barbus’ groups investigated. While some taxa do appear to be amphi-Guinean others are restricted to one ichthyo-province or the other. Numerous headwater capture events within the area have allowed taxa to expand ranges and diversify. This study also provides insights on areas of endemism within the region where additional undiscovered diversity is likely to occur. / acase@tulane.edu

Weak bonds such as hydrogen bond, pi-pi stacking and van der Waals interaction are much weaker in the strength but play a more important role for the existence of various lives. For example, they are the major intermolecular interactions in the liquid and solid structure of water and determine the 3 dimensional structure of protein and DNA, which are the crucial organic molecules in lives. As a result, studying these weak bonds can lead to the better understanding of fundamental knowledge of lives. Kohn-Sham (K-S) Density Functional Theory (DFT) is an accurate and effect way to investigate the fundamental properties for many-body systems, in which, only the exchange-correlation energy as a functional of electron density need to be approximated. However, weak interaction system is still a challenge problem for KS-DFT. In this dissertation work, several standard density functionals are used to study these weak interactions in the solid state structure ice as long as nucleic bases molecules in the biologic system. It is found that the hydrogen bond can be well described by most semilocal functionals: the mismatch problem of ice Ih and AgI for GGA functional can be solved by using the higher level meta-GGA functionals and the binding length and energy between nucleic bases in DNA can be well described. However, the more accurate dispersion correction is strongly needed for van der Waals interactions and pi stacking for super-high pressure ice phases and large size biologic molecules, where van der Waals interaction takes major role. Finally, the basic structural properties of various phases of ice and DNA can be understood based on the investigation with appropriate functionals. / acase@tulane.edu

Soft tissue reconstruction in the nervous system is sensitive to the mechanical and chemical cues of the growth microenvironment. Many technologies have been designed to study these stimuli and their effect on the regional extracellular environment (ECM). Because of the hard-to-achieve and costliness of these technologies, biologists are usually reluctant to employ them to study cellular behaviors. In addition, the complexity of the nervous system, particularly in cases of nerve repair and reconstruction, necessitates the development of facile high- throughput investigational tools. The objective for this dissertation is to examine and manipulate neuronal cell-cell and cell-ECM responses to varying nervous system microenvironment stimuli in a 3-D in vitro model. / acase@tulane.edu