Young people spend two-and-a-half as much time watching Internet videos as they do traditional television. Business concerns aside, questions remain about other effects of this change in media consumption. One such concern is of celebrities and their influence. Research demonstrates that celebrities are influential, in part because people consider them credible sources, even with regard to political information. Research also shows that a credible source is more effective at changing one’s attitude and behavioral intention than a low-credibility source. These research findings might alter what was previously perceived as the influence of traditional celebrities – movie stars, pop groups, and the entertainment industry as a whole. With the growth of particular participatory platforms and social media sites, a new type of celebrity exists: microcelebrity. Defined as an act of bolstering digital self-representation through media and technology, the term microcelebrity has since evolved to include individuals who construct self-representation and garner popularity online. Although there is a great deal of research demonstrating that microcelebrities are also influential, especially regarding consumer good purchases on social media, the question of microcelebrity influence on politics remains. In a two by two experiment, this study starts with a literature review on credibility, traditional celebrity, their political influence on audiences, followed by an introduction to microcelebrities and their influence, with a method section that leads to a few hypotheses. First, according to past literature, it is hypothesized that traditional celebrities are evaluated as more credible than microcelebrities. Second, male celebrities (both traditional and microcelebrities) are expected to be evaluated as more credible than female celebrities. Third, traditional male celebrities will be more credible than any other kind of celebrity. Given credibility is deemed by scholars as a crucial component of persuasion, assessing microcelebrities’ credibility provides a better understanding of their societal and political mpact.

The misfolding and aggregation of free light-chains into amyloid fibrils is the hallmark of antibody light-chain (AL) amyloidosis, a fatal disease associated with the accumulation of amyloid species in tissues throughout the body, including the heart and kidneys. Current treatment options, including chemotherapy and bone marrow transplant, do not address the causes of aggregation on a molecular level. Molecular dynamics (MD) simulations were used to investigate misfolding pathways in the aggregation of two light chain monomers, Jto and Wil. These simulations showed that under amyloidogenic conditions, conversion from beta-sheet to alpha-sheet secondary structure was observed in both Jto and Wil. Misfolded conformations, obtained from the MD simulations, were used to guide the design of alpha-sheet peptides, which have been used previously to inhibit amyloid formation in diverse systems. The designed peptides were evaluated computationally by docking them against misfolded conformations of Wil, and the best performing peptide was chosen for future experimental work to explore its potential to limit aggregation.

Type 2 diabetes (T2D) is a disease associated with pancreatic islet β-cell failure; especially, the loss of β-cell mass. Approximately 75% of patients who start with one medication will need multiple to control the progression of this disease. With no cure and numerous secondary complications - blindness, kidney failure, heart attack, and stroke - T2D places an enormous burden on our society and healthcare system today; The disease is projected to be the seventh leading cause of death by 2030. Islet amyloid polypeptide (IAPP) deposition is observed in approximately 90% of T2D patients. While human IAPP (hIAPP) is amyloidogenic, forming amyloid fibrils and deposits, IAPP from rodents is not. Our group’s previous findings suggest that T2D and other amyloid diseases form soluble toxic oligomers through a non-standard α-sheet secondary structure. We propose a peptide-based therapeutic to combat T2D via utilizing synthetic α-sheet compounds complementary to the amyloid-associated α-sheet structure to target the toxic oligomer form of hIAPP. In this study, we addressed the efficacy of this peptide-based therapeutic through inhibiting the aggregation of hIAPP via a Thioflavin-T assay and neutralizing the hIAPP oligomer cytotoxicity via a MTT cell viability assay in a human-derived pancreatic cell line. The preliminary results suggest that our peptides are effective in reducing hIAPP aggregation and oligomer cytotoxicity. Moving to a more biologically relevant model, we evaluated the effects of our compounds on reducing amyloid formation in the islet of Langerhans from transgenic mice; the preliminary results are encouraging. The α-sheet platform provides a novel potential therapeutic for treating T2D and other amyloid diseases.

Streptococcus mutans is an acidogenic bacterial species that predominates in the oral microbiome. S. mutans binds to the salivary pellicle, a layer of proteins that forms on the tooth surface and forms acids after metabolizing sugars. Accumulation of S. mutans biofilms leads to cavity formation, and when the bacteria travels to and infects the heart, can lead to infectious endocarditis. Therefore, decreasing accumulation of S. mutans is a key concern. Recent evidence suggests that S. mutans is among the bacterial species that utilize functional amyloid fibrils in its biofilms. Amyloids are insoluble fibrillar protein aggregates with a cross-ß structure, and functional amyloids are used by bacteria to provide structure and strength to their biofilms. While functional amyloid systems in bacteria such as E. coli and S. aureus have been investigated, very little is known about the mechanism or purpose of S. mutans functional amyloids. Polyphenolic small molecule epigallocatechin gallate, or EGCG, is an amyloid inhibitor in S. mutans biofilms. Previous results from our lab suggest that amyloid fibrillization progresses via an intermediate that adopts a unique secondary structure, an alpha-sheet. Alternating L- and D- amino acid peptides adopt an alpha-sheet secondary structure and have been shown to inhibit amyloid formation in multiple mammalian systems by binding to soluble alpha-sheet-containing oligomeric species. Inhibition of amyloid formation by alpha-sheet peptides suggests presence of an alpha-sheet intermediate species on the pathway to functional amyloid formation. To investigate the mechanism of functional amyloid formation in S. mutans, alpha-sheet peptide inhibitors were compared to EGCG for their ability to inhibit fibril formation of S. mutans adhered to an artificial salivary pellicle.

Alzheimer's disease affects millions of individuals worldwide, yet there is an astounding lack of marketed treatments that can effectively slow the neurodegeneration associated with the disease. In the past few decades, evidence has emerged that small, soluble aggregates of beta-amyloid (Aβ) peptide known as oligomers are primarily responsible for toxicity in the brain, which has sparked research to develop inhibitors targeting the toxic oligomers. However, the actual structure of Aβ oligomers remains unknown, in large part because traditional methods used to determine protein structure are ineffective due to the dynamic and heterogeneous nature of these oligomers. This in turn has greatly hindered therapeutic development. Interestingly, a designed α-sheet peptide known as AP3 displays striking behavioral similarities to Aβ under low pH, making it an ideal model for understanding amyloid protein behavior. In addition, AP3 aggregation and toxicity are potentily inhibited by other amyloid species. The interactions between this synthetic amyloid and naturally-occurring amyloid species, including Aβ, are being explored both experimentally and via computer simulation, and the data are being used to design a de novo peptide inhibitor. This inhibitor is being tested for its ability to inhibit amyloid aggregation and toxicity, as well as whether it can specifically bind to heterogeneous populations of Aβ even at low concentration. The successful completion of this project wil result in significant progress towards understanding amyloid behavior and aggregation. This may eventually lead to novel applications of the α-sheet structure in treatments and diagnostic assays for Alzheimer's.

Computational simulations of protein dynamics provide an efficient way of predicting protein behavior and are increasingly being applied to peptide and protein design. However, design tools and software focus on static structures. Incorporation of dynamics directly or through design libraries derived from dynamics simulations allows the user to focus on optimization of the native dynamics of the protein for a specific purpose. Critical libraries for design, such as side chain rotamer libraries and amino acid propensities are typically derived from static structures, which do not reflect behavior in dynamic conditions. Therefore, including rotamers and conformational propensities derived from behavior during protein simulations in molecular modeling and design software should improve the design process and outcome, particularly for peptides. Additionally, current software does not allow the user to adjust the main chain dihedral angles of the backbone according to Ramachandran plots reflecting the unique free energy landscape of each residue. The WRANGLER software was designed in order to include dynamic data to better model and design against and for dynamic systems. A number of libraries derived from dynamics simulations of all known protein folds have been incorporated. In addition, the software is interactive with a graphical interface to easily change and visualize geometries and analyze peptide/protein properties. WRANGLER was evaluated based on ability to facilitate design of several amyloid peptide aggregation inhibitors. Resulting designs were evaluated through molecular dynamics simulations for their secondary structure retention and physical properties. Control amyloid peptide aggregation inhibitors were included that have already been designed, synthesized and tested experimentally in lab. Several peptides designed in WRANGLER appear to be better than the controls by a variety of metrics. The next step is to synthesize these new designs and test them against the amyloid-beta peptide associated with Alzheimer’s Disease to see if they outperform our current compounds.