Foot pathology is a real problem in captive elephants. Osteoarthritis is the major concern among musculoskeletal disorders and foot health problems for elephants in North America zoos with one-‐half of Elephants in captivity showing foot health care problems in zoos. A higher ratio of captive Asian elephants (Elephas maximus) is...
Pactamycin, a potent antitumor antibiotic produced by the soil bacterium Streptomycespactum, is a structurally unique aminocyclopentitol-containing natural product. Itconsists of a highly functionalized cyclopentitol core unit, two aromatic rings [3-aminoacetophenone (3AAP) and 6-methylsalicylic acid (6MSA)], and a 1,1-dimethylurea moiety. Despite its potent biological activity, the development of thisantibiotic was hampered...
The discovery of new antibiotics reached its peak during the golden era of antibiotics in the mid 20th century and continued to thrive until the 1980s. However, after more than 50 years of fruitful exploration and exploitation of microbial natural products the discovery rate of new antibiotics has dropped drastically...
This thesis describes an investigation of the natural products chemistry of two fungal species of the genus Tolypocladium. Natural products are small organic molecules that are considered non-essential for cell growth and reproduction, and thus part of secondary metabolism. Chemical profiling of these secondary metabolites using a combination of high-performance...
Mammalian skin is the largest organ of the body and serves as a barrier to protect the body against chemical, mechanical and pathogenic insults as well as water loss. The epidermis is formed from the primitive ectoderm into a multilayered stratified epithelium, consisting of basal, spinous, granular and outermost cornified...
Poor aqueous solubility of a large number of newly discovered chemical entities is posing a significant challenge for the formulation industry and is delaying their drug development. The number of formulation techniques available to solubilize these poorly soluble molecules is very limited. In addition to that, traditional formulation methods involve...
Natural products from both terrestrial and marine sources represent a significant source of novel drug leads, and have previously been developed into clinically-approved agents for the treatment of various human diseases. This work represents the biological characterization of the mechanistic basis for activity of several natural product structures in models...
Clostridium perfringens is a spore-forming pathogenic bacterium that causes a variety of diseases in human and animals. C. perfringens type A isolates produce enterotoxin (CPE) causing food poisoning (FP) and non-food-borne (NFB) gastrointestinal (GI) diseases including antibiotic-associated diarrhea and sporadic diarrhea. C. perfringens type A food poisoning currently ranks as...
Perinatal growth restriction programs higher risk for chronic disease during adulthood via morphological and physiological changes in organ systems. Perinatal growth restriction is highly correlated with a decreased nephron number, altered renal function and subsequent hypertension. I hypothesize that such renal maladaptations result in altered pharmacologic patterns for life. Pregnant...
This thesis describes an investigation of the molecular basis of the substrate specificity and catalytic mechanism of a unique pseudoglycosyltransferase (PsGT) enzyme, VldE. PsGTs are a newly discovered group of glycosyltransferase (GT)-like proteins that catalyze the transfer of a pseudosugar to an acceptor molecule via a C-N bond formation. This...