Differences in Research on Post-Traumatic Stress Disorder: How Trauma-Type and Sex Contribute to the Published Research

There is a pervasive and comprehensive history of sexism in the pursuit of scientific truth, extending back beyond the days of “hysteria” and continuing still. Herein, we discuss a disparity in scientific research on a disorder thought to affect less than 8% of the adult population in the USA with the number of women diagnosed with the disorder estimated to be two to three times higher than that of men. While post-traumatic stress disorder (PTSD) is more likely to be experienced by women, we find that the overwhelming majority of published scientific literature on PTSD involves male combat veterans. For example, since March 2019, according to a widely used medical research search engine, specifically the electronic database PubMed (https://www.ncbi.nlm.nih.gov/pubmed/), over 1,100 articles can be found with the keywords, “veteran and PTSD” while using the keywords, “sexual assault and PTSD” yields a little over 100 total articles. While not all victims of sexual assault are female and not all combat veterans are male, the majority sex in each category is such that much of the research on “veteran” was specifically carried out with male veterans and much of the work on “sexual abuse” was carried out exclusively with females. This creates a perception that both overinflates the incidence of PTSD experienced by male combat veterans and underemphasizes the experience of PTSD in female victims of sexual assault. Differences in symptoms of PTSD do vary by war and what little research exists on PTSD after sexual assault suggests that it is likely that symptoms as well as associated comorbidities will vary depending on the cause, type, number, and age at first trauma, among other factors. This study focuses on the specific comorbidities of pain, addiction, and immune function in those who experience PTSD following war-based or sexually-based traumas. It is our hope that in reviewing the currently available research, we spotlight the need for research focused on PTSD experienced after sexual assault. Doing so has the potential to lead to better and more tailored treatments for PTSD, thus enriching outcomes for all sufferers of PTSD

Alpha B-crystallin protects retinal tissue during Staphylococcus aureus-induced endophthalmitis

Bacterial infections of the eye highlight a dilemma that is central to all immune-privileged sites. On the one hand, immune privilege limits inflammation to prevent bystander destruction of normal tissue and loss of vision. On the other hand, bacterial infections require a robust inflammatory response for rapid clearance of the pathogen. We demonstrate that the retina handles this dilemma, in part, by activation of a protective heat shock protein. During Staphylococcus aureus-induced endophthalmitis, the small heat shock protein αB-crystallin is upregulated in the retina and prevents apoptosis during immune clearance of the bacteria. In the absence of αB-crystallin, mice display increased retinal apoptosis and retinal damage. We found that S. aureus produces a protease capable of cleaving αB-crystallin to a form that coincides with increased retinal apoptosis and tissue destruction. We conclude that αB-crystallin is important in protecting sensitive retinal tissue during destructive inflammation that occurs during bacterial endophthalmitis

The Role of Crystallins and Fas Ligand in Protection versus Ocular Destruction in Endophthalmitis

Apoptosis is a genetically regulated mechanism by which cells commit suicide. Thus, cellular responses to apoptosis may be critical to the treatment of multiple diseases. However, inhibitors of apoptosis are commonly expressed in many disorders, conferring cellular survival and resistance to death. A well-known mechanism by which apoptosis is derailed in many cell types is through increased expression of cellular stress proteins, including heat shock proteins. During my postdoctoral fellowship, we identified the heat shock protein aB-cystallin as a novel inhibitor of apoptosis. Recently, colleagues at Schepens Eye Research Institute demonstrated an upregualation of crystallin expression in the eyes of mice during inflammation in a model of bacterial induced endophthalmitis, an intraocular bacterial infection that can lead to complete destruction of the eye. Experiments described herein will examine the hypothesis that upregulation of crystallins confers protection to the retina during destructive inflammation secondary to endophthalmitis

Research Academy for Teachers (RAFT): A Wild Ride and Fun Summer Experience

This workshop showcases an experimental biology course designed to target Masters of Arts in Teaching-Biology students. The overall goal was to provide high school teachers with a research-rich laboratory experience to more deeply explore cellular biology. Since understanding of cellular processes is augmented with hands-on training, RAfT was designed to improve understanding of cellular biology and to allow participants to apply techniques using advanced instrumentation (immunoblot, flow cytometry, microscopy). Over the course of seven weeks, participants immersed themselves in the primary literature, designed experiments using the scientific method and ultimately, applied techniques they learned to address a concrete research question of their own choice with focused cellular endpoints. Focus Groups with participants have been overwhelmingly positive, indicating that teachers feel more comfortable and confident in teaching cell biology to their students. The inquiry-based strategy used in this course may be used as a model for other graduate and undergraduate courses

Making Connections: Comparative Innovations in the Sciences

Looking into the Crystallin Ball: Elucidating the Role of aB-crystallin in Inflammasone Activation in Retinal Epithelial Cells Dr. Merideth Krevosky, Dr. Jeffery Bowen Inhibitors of apoptosis are upregulated in cancer, conferring cellular survival, and are downregulated in neurodegenerative and inflammatory diseases such as age-related macular-degeneration (AMD) which are characterized by increased cell death. The small heat shock protein, αB-crystallin inhibits apoptosis by disrupting activation of an enzyme critical for cell destruction. Previous work demonstrated αB-crystallin cleavage and inactivation is coincident with destructive endophthalmitis and loss of retinal function, supporting αB-crystallin’s cytoprotective role in the retina. Research implicates inflammation in retinal destruction during AMD which involves a protein complex known as the inflammasome. Studies are underway to address whether αB-crystallin interacts with inflammasome complex proteins. Our current studies support that αB-crystallin is localized to and cleaved within cellular lysosomes during inflammasome activation, supporting that loss of αB-crystallin correlates with retinal cell destruction. Since few therapeutic interventions exist for AMD, modulation of αB-crystallin expression may promote retinal cell viability and prevent vision loss. Rapid Fooling Around in the Presence of Competitors Favors Breakups Dr. Thayaparan Paramanathan The title makes common sense with human behavior, but is this true for the breaking apart of non-covalent complexes in biological systems? The formation and breaking apart of these non-covalent complexes is a key determinant of functions in molecular biology and pharmacology. Dissociation rates of complexes are conventionally assumed to depend only on the interactions between the molecules forming the complex, and not on the presence of competitors. We use a single-molecule technique, where we label the molecules with fluorescent dyes of different colors and shine them with the appropriate laser color to watch them individually. Our results suggest that, indeed, the competitor accelerates dissociation of a non-covalently bound molecular complex by occluding the rapid rebinding of binding partners. The results show that an acceleration of ligand dissociation rate with increasing competitor concentration is a natural feature of a molecular competition that can occur in biologically relevant ranges of competitor concentration

External Funding: When is the Time Right?

This panel of faculty and OGSP personnel will discuss external funding readiness, available support, and the influence of external funding upon professional growth. Specifically, the following questions will be discussed: 1) How has the pursuit/receipt of external funding changed your research, scholarship, and/or teaching? 2) How did you know that you were ready to pursue external funding? 3) In the process, what kinds of support did you need from the OGSP

The Small Heat Shock Protein B-crystallin Is a Novel Inhibitor of TRAIL-induced Apoptosis That Suppresses the Activation of Caspase-3

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor α family of cytokines that preferentially induces apoptosis in transformed cells, making it a promising cancer therapy. However, many neoplasms are resistant to TRAIL-induced apoptosis by mechanisms that are poorly understood. We demonstrate that the expression of the small heat shock protein αB-crystallin (but not other heat shock proteins or apoptosis-regulating proteins) correlates with TRAIL resistance in a panel of human cancer cell lines. Stable expression of wild-type αB-crystallin, but not a pseudophosphorylation mutant impaired in its assembly and chaperone function, protects cancer cells from TRAIL-induced caspase-3 activation and apoptosis in vitro. Furthermore, selective inhibition of αB-crystallin expression by RNA interference sensitizes cancer cells to TRAIL. In addition, wild-type αB-crystallin promotes xenograft tumor growth and inhibits TRAIL-induced apoptosis in vivo in nude mice, whereas a pseudophosphorylation αB-crystallin mutant impaired in its anti-apoptotic function inhibits xenograft tumor growth. Collectively, these findings indicate that αB-crystallin is a novel regulator of TRAIL-induced apoptosis and tumor growth. Moreover, these results demonstrate that targeted inhibition of αB-crystallin promotes TRAIL-induced apoptosis, thereby suggesting a novel strategy to overcome TRAIL resistance in cancer