Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 15-16). / Traumatic brain injuries are one of the most common injuries in domestic violence, with studies finding that approximately 75 percent of women tested report at least one TBI. These injuries leave invisible scars in the form of memory problems. But despite the large prevalence of TBIs in the population, there is a lack of research, stunted by both funding and a lack of subjects. The trouble with research extends to chronic traumatic encephalopathy, a degenerative disease caused by repetitive hits to the head. Although domestic violence researchers suggest that the population will develop CTE, which is only diagnosed post-mortem, a lack of donated brains means the disease has yet to be found among domestic violence victims. / by Heather Mongilio. / S.M. in Science Writing

Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 22-26). / Sustainable food movements are focused on reducing meat consumption for one simple reason: meat is extremely environmentally costly. This enormous resource use by one industry makes it an appealing target for those looking to reduce American resource use. As a result, many are looking at ways to make livestock more sustainable. And there are two main ways to do so. Clover Food Lab represents one idea: a return to local farming with an emphasis on a plant-based diet. Impossible Foods is the second: using biotechnology to provide a sacrifice free alternative, synthetic beef. These companies aren't solutions in of themselves, but proposals on the way solutions should be implemented. The partnership between these two opposing strategies reveals the promises and pitfalls of trying to reform the American diet and, most importantly, that above all else our food system is unsustainable as it is now. / by Ashley Junger. / S.M. in Science Writing

Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 19-23). / Metals mined from the seafloor could support tomorrow's technological and clean energy innovations. Though the mineralogical and geochemical significance of seafloor deposits, which lie thousands of meters below the water's surface in geological formations such as polymetallic nodules, ferromanganese crusts, and seafloor massive sulfides is well-established, the biological and ecological profiles of these sites are still actively developing. As a result, the two scientific disciplines - geochemistry and biology - have advanced at different rates. Regions of the seafloor including the Clarion-Clipperton Fracture Zone, the Prime Crust Zone, and inactive or waning hydrothermal vent systems have attracted attention for their unique concentration of metals used in electronics and strong magnets. With commercial mining activities set to commence in 2019 by Canadian company Nautilus Minerals, it is time to assess the paradoxical nature of seafloor mining: to mine the seafloor to support sustainable and efficient technological development on the land above. / by Fatima Husain. / S.M. in Science Writing

Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 21-26). / Cabo Pulmo National Park is a 27-square mile protected area in the Gulf of California, near the southern end of Mexico's Baja Peninsula. The park surrounds one of the oldest coral reefs on the western coast of North America. Once damaged and depleted by overfishing, the reef has seen an incredible recovery since its protection in 1995. This recovery is due in large part to the efforts of the very people who once fished the reef. The adjacent community of Cabo Pulmo, in collaboration with a group of scientists from the Universidad Autónoma de Baja California Sur in La Paz, Mexico, requested the marine protected area, acted as vigilante enforcers for the park's rules, and worked to prevent proposed developments that might damage the ecosystem. As the ecosystem has recovered, they have been able to reap the economic benefits of the park, opening dive shops and restaurants. The story of their struggles and triumphs can provide valuable lessons for community-based conservation efforts around the world. / Laura Castañón. / S.M. in Science Writing

Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2018. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages [17]). / Before much of America learned to fear atomic energy, towns like Perry, Ohio, learned to love it. For over thirty years the Perry Nuclear Power Plant has been the linchpin of the small Rust Belt community, bringing flush budgets and well-paying jobs to an area with little other industry. But like many nuclear power plants in the U.S., the Perry plant is aging, costly to maintain, and unable to compete with the nearly two-decade run of record-low natural gas prices. On the isolated shores of Lake Erie, Perry is now caught in a global energy shift. In the coming years, more than two-thirds of the nuclear power plants in America are similarly at risk of shut down, the consequences of which will leave deep voids in the diversity of America's energy grid and depleted tax bases in the rural towns that house nuclear power plants. Residents and town officials in Perry, however, are not going quietly into the retrenchment of America's nuclear energy industry. / by Kelsey M. Tsipis. / S.M. in Science Writing

Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2021. / The concept of science evokes forward momentum, a steady march of progress as scientists accumulate knowledge, refine hypotheses, and make theoretical leaps. But science, it turns out, can also meander as much as a wandering bird. / Illustrating this concept is research on the European starling, a migratory species whose annual travels have been helping shape the field of bird migration science for the past hundred and twenty years. Starling research, from early bird banding to current satellite tracking efforts, has been marked by moments of controversy and confusion alongside insight and discovery. Following starlings — and the researchers who study them — reveals the hidden twists and turns that characterize the path to scientific understanding. / by Alice D. McBride. / S.M. in Science Writing

Burkholderia pseudomallei (Bp) is a major public health concern in the endemic regions of southeast Asia and northern Australia, yet the organism has a worldwide distribution and cases are likely under-reported. In northeast Thailand the mortality rate associated with Bp infection is over 40%. The inherent resistance of Bp to multiple antibiotics impairs treatment, and relapse is seen in more than 25% of survivors. Beyond its public health significance, Bp is considered a potential biological warfare agent by the U.S. DHHS and was recently listed as a Tier 1 select agent. Despite enhanced research and vaccine efforts, traditional vaccine strategies employing attenuated bacterial strains, recombinant proteins, or purified polysaccharides have failed to elicit complete protection against aerosol challenge with Bp. We have previously shown that immunization with outer membrane vesicles (OMVs) derived from Bp can protect mice from lethal melioidosis. In this work we characterize the interactions of OMVs with antigen presenting cells in order to elucidate innate immune responses to the OMV vaccine. Vaccine-mediated antibody responses and protective efficacy were characterized in BALB/c mice. We also tested the safety and immunogenicity of the OMV vaccine in non-human primates (NHP). We show that Bp OMVs interact with dendritic cells and macrophages and are internalized by these antigen presenting cells (APCs).Internalization is dependent on actin polymerization and cholesterol present in APC membranes. OMVs also upregulate MHC class I and II on APCs, as well as promote the production of pro-inflammatory cytokines in a TLR2/4 dependent manner. Immunization of mice with Bp OMVs by the s.c. and i.m. routes induced the production of OMV-specific IgM and IgG and significantly protected mice against aerosol challenge. Addition of alum and MPL did not significantly change the antibody profiles of immunized mice and did not significantly enhance vaccine mediated protection. OMVs were well tolerated in a large animal NHP model. There were no adverse clinical reactions, and NHPs mounted significantly increased levels of OMV-specific IgG and OMV specific CD4+ T cell responses. These results suggest that Bp OMVs can stimulate innate and adaptive immune responses and may represent a safe and efficacious vaccine against melioidosis / acase@tulane.edu

Rupture of atherosclerotic plaque can cause acute life-threatening events such as myocardial infarction and ischemic stroke; therefore, there is much interest in developing therapies aimed at increasing plaque stability. More stable lesions are characterized as having high collagen content and containing a large number of vascular smooth muscle cells (SMCs) of contractile/differentiated phenotype. In our previous studies using an apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis, we found that insulin-like growth factor-1 (IGF-1)-infusion not only reduced total plaque burden, but also increased collagen expression and the number of alpha-smooth muscle actin (αSMA)-positive cells in plaque. In this study, we identify cellular mechanisms responsible for these observations. We found that in human aortic smooth muscle cells (HASMCs) grown in culture, IGF-1 post-transcriptionally upregulated expression of the procollagen type I alpha-1 subunit (pro-α1(I)) as well as contractile proteins, αSMA and smooth muscle 22-alpha (SM22α), via a PI3K-dependent but Erk1/2- and mTOR-independent signaling mechanism. Furthermore, experiments using an inhibitor of collagen synthesis or a blocking antibody against the alpha2beta1-integrin (α2β1) suggested that interaction with collagen type I promotes HASMC contractile phenotype. To elucidate mechanisms underlying IGF-1 upregulation of collagen synthesis we investigated the effect of IGF-1 on the mRNA-binding protein, la ribonucleoprotein domain family member 6 (LARP6), which had been shown to bind a conserved stem-loop secondary motif in the 5’UTR of COL1a1 and COL1a2 mRNA. IGF-1 rapidly increased LARP6 expression in HASMCs leading to increased COL1a1 and COL1a2 mRNA bound LARP6 and increased synthesis of collagen type I. Mutation of the 5’stem-loop of Col1a1 mRNA (that inhibited binding by LARP6) or overexpression of a 5’stem-loop RNA molecular decoy (that sequesters LARP6) both prevented the ability of IGF-1 to increase pro-α1(I) synthesis as well as mature α1(I) expression in cultured medium. Furthermore, IGF-1-infusion in Apoe-/- mice increased LARP6 and pro-α1(I) expression in aortic lysates, and SMC-specific IGF-1-overexpression in transgenic mice robustly increased collagen fibrillogenesis in atherosclerotic plaque. In conclusion, this work identifies LARP6 as a critical mediator by which IGF-1 augments synthesis of collagen type I in vascular smooth muscle, and uncovers key mechanisms whereby IGF-1 promotes atherosclerotic plaque stability. / acase@tulane.edu

Lyme disease is the most commonly reported vector-borne disease in the United States. The causative agent of Lyme disease, can alter gene expression to enable survival in a diverse set of conditions, including the tick midgut and the mammalian host. External environmental changes can trigger gene expression in B. burgdorferi, and the data demonstrate that B. burgdorferi can similarly alter gene expression as a stress-response when it is treated with the antibiotic doxycycine. After treatment with the minimum bactericidal concentration (MBC) of doxycycline, a subpopulation can alter its phenotype to survive antibiotic treatment, and to host adapt and successfully infect a mammalian host. Furthermore, our data demonstrate that if a population is treated with the MBC of doxycycline, a subpopulation may alter its phenotype to adopt a state of dormancy until the removal of the antibiotic, whereupon the subpopulation can regrow. We demonstrate that the chance of regrowth occurring increases as a population reaches stationary phase, and present a mathematical model for predicting the probability of a persister subpopulation within a larger population, and ascertain the quantity of a persister subpopulation. To determine which genes are expressed as stress-response genes, RNA Sequencing analysis, or RNASeq, was performed on treated, untreated, and treated and regrown B. burgdorferi samples. The results suggest several genes were significantly different in the treated group, compared to the untreated group, and in the untreated and regrown group compared to the untreated group, including a 50S ribosomal stress-response protein, coded from BB_0786. The appendices discuss the theory and methods that were used in RNA Sequencing (RNASeq) analysis, and provide an overview of the database that was created for the B. burgdorferi transcriptome. Additional studies may demonstrate further how persister subpopulations form, and which genes can trigger a persister state in B. burgdorferi. / acase@tulane.edu

Profound vascular leakage in conjunction with elevated viremia is the hallmark of Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS). Antibody (Ab)-dependent enhancement (ADE), in which pre-existing, cross-reactive Abs enhance virus infectivity, is thought to be responsible for increased viremia, while loss of endothelial cell (EC) barrier integrity is the precursor to plasma leakage. However, the relationship between viremia and vascular leak has not been established. The objective of this dissertation project was to determine the involvement of antibodies in the pathogenesis of vascular leak syndrome associated with DHF/DSS by establishing a relationship between Ab-mediated increase in viremia and changes in vascular permeability, the hallmark of DHF/DSS. Our approach focused on characterization of human monoclonal antibodies (hMAbs) from a previously dengue virus (DENV)-infected patient for their ability to both neutralize and enhance infection and increase vascular permeability in vitro. Our results revealed that the human antibody response to DENV E protein elicited by natural infection is predominantly comprised of broadly cross-reactive antibodies targeting domain II epitopes. Using a multiplex cytokine immunoassay, qRT-PCR, and plaque assay, we demonstrated an association between viral load and cytokine production in DENV-infected FcγR-bearing K562 cells, and determined that DENV infection of K562 cells in the presence of hMAb resulted in a modulated inflammatory cytokine response with an overall pro-inflammatory profile. Using human microvascular ECs (HMEC-1), we further demonstrated an association between viral load, cytokine production, and the onset of permeability changes via an indirect mechanism in which inflammatory mediators released by DENV-infected K562 cells altered HMEC-1 barrier function and observed a synergistic effect between active DENV infection and release of inflammatory mediators by both K562 and HMEC-1 that increased permeability. Collectively, our results support the multifactorial nature of the pathogenesis underlying vascular leak, involving a complex interaction between ECs and FcγR-bearing cells, and a synergistic relationship between enhanced viremia and inflammatory mediators leading to increased permeability. Our use of hMAbs provided a novel approach to understanding how Abs impact the vasculature during DENV infection and enable identification of Ab characteristics that may trigger vascular leak, a crucial concern for DENV vaccine design. / acase@tulane.edu