Somers Science Research Podcast

Science Research Senior, Raghav Nathan, talks about his time in the Science Research program at Somers High School, his research on the role played by referential integration and referential ambiguity in RNP using ERP and eye tracking analysis, and his plans for after graduation. 

Forensic diptera entomology is the study of flies as they decompose in carcasses, primarily used in forensic science to determine how long the organism these flies are inhabiting has been deceased. Decomposition rates can vary widely for numerous natural reasons, which are commonly studied by entomologists, along with comparing single species to each other. This study, in contrast, compares single species to a community of species to determone if there is a diffrence between decomposition rates when there are other fly species present versus when only one species is present. It was hypothesized that the single species, Sarcophaga bullata, would decompose at a faster rate than that of the community of Calliphoridae (Wildlife) species. In this study, the single species Sarcophaga bullata was used to represent the lab setting, and the community of Calliphoridae flies was used to represent the natural setting. Over the course of four months, ground beef was placed in fly cages and once removed, allowed to sit for two weeks. The initial and final weights were measured to determine the percentage of meat decomposed over this time period for each species. It was found that although the s.bullata had higher average decomposition rate, the p-value was greater than 0.05 (p=0.416), meaning that there was not a statistical significance between the single species versus the community species. 

Immune checkpoint inhibitors such as Atezolizumab have had tremendous success; however, they cause increasingly toxic immune related adverse events (irAEs) depending on the inhibitor used. Pharma companies should recognize that a cause of Atezolizumab’s (TECENTRIQ) irAEs could be that it blocks the two overlapping binding sites of PD-1 and B7-1. Recent studies reveal a novel pathway between PD-L1 and B7-1, resulting in the inhibition of T cell proliferation and cytokine secretion. Blocking more than one pathway can activate significantly more T cells than expected. Although this benefits patients who tolerate the irAEs, many patients cannot. The solution is to create an antibody binding to PD-L1 in a non-overlapping region, where only PD-1 or B7-1 should bind. Previously, part of the binding site of B7-1 on PD-L1 was discovered, but not enough residues were known for a complete picture of the non-overlapping region for drug development. Recently, several amino acids were mutated, creating a more complete picture of the site of B7-1 on PD-L1. The FDA approved drug Atezolizumab was tested to determine which residues it binds to on PD-L1. With this information, new drugs can be produced blocking only one pathway instead of two, resulting in fewer immunotherapy side effects.

Chronic stress involves a response to emotional pressure experienced for a long period of time. It is also a source of depressive disorders. Recent studies have suggested that chronic stress does not only have mental impacts, but also molecular impacts, specifically on cognition. In this study, it is hypothesized that chronic stress does have an influence on cognitive function. From hippocampal samples of repeated social defeat stressed mice and control mice, both mRNA levels and protein levels were analyzed. RNA was isolated, reverse transcribed, and a real-time quantitative PCR was conducted. For the proteins, after isolation, a BCA protein assay was conducted, and then multiple western blots were performed to observe their expression. Afterwards, data were collected and analyzed. A student’s t-test was performed to determine the significance of any change observed in the stressed mice. BDNF V, Synapsin 1 and Synapsin 2, at the mRNA level, were found to be significantly downregulated. At the protein level, pCREB was found to be surprisingly upregulated in the stressed mice. Overall, this chronic stress does impact cognition, but only to a certain extent and in variation.

The WHO rated depression as the fourth greatest public health problem in 2014, and the leading cause of disability in industrialized countries.  Sleep deprivation is a lesser known cure for depression, but one that has been proven to work in 60% of the population, and to decrease symptoms by 50%.  However, the mechanisms behind this phenomenon are unknown, so my study will look into the neurological pathways responsible.  For my study, I will be taking 13 depressed patients and 3 controls into the sleep laboratory at the University of Pennsylvania.  There they will stay for 5 days for 4 nights (one sleepless).  They will take two different types of tests- Hamilton Rating Scale for Depression (HRSD) tests, which look into changes in depression, and Balloon Analog Risk Task scans (BART), which look into changes in the risk activation, which is directly related to the putamen. My data shows that there is a clear correlation between putamen activation and an increase in mood.  This direct relationship can be shown on a graph with an R2 value of .27. The contributions of my project are large, as my study can help create a cure for depression that can help up to 60% of the population.  My data will be used to create a treatment that stimulates the Putamen in a similar way that sleep deprivation did, and can help increase mood.