Approaches to Justice

Approaches to Justice How do we seek justice in this country? What issues surround incarceration? How are the effects of mass incarceration felt in local communities? I am currently addressing these research questions, among others, as I engage with the criminal justice system through my year-long research at Emory’s Oxford College and in prisons and with nonprofits throughout Georgia. I am reading and evaluating texts centering around theories of incarceration, the death penalty, and criminal justice reform, including Bryan Stevenson’s Just Mercyand Michelle Alexander’s New Jim Crow. I also interned with The Georgia Innocence Project this past summer and will use my experience to propel my research. I was selected to participate in the Oxford Research Scholars program where I am working with Sarah Higinbotham, a professor at Oxford College who directs a statewide college-in-prison program; I will join her as she teaches at Georgia prisons to gain more experiential knowledge about incarceration. Why is criminal justice research relevant? The United States incarcerates more people per capita than any other country, meaning very few people live their lives without encountering the system. Therefore, it is crucial that we understand how our country seeks justice and examine to what extent this system is sustainable. At the 2018 Georgia Undergraduate Research Conference, I propose to present my ongoing research on justice and the criminal justice system. I will discuss how I became interested in criminal justice reform despite the unlikelihood I will ever come into contact with the system. I will also describe my experience engaging with people who are incarcerated at Georgia prisons as well as working with the Georgia Innocence Project. I plan to discuss the texts I have engaged with thus far: Just Mercy, New Jim Crow, andA Colony in a Nation.I will also ask for any feedback from the audience on the direction in which I should take my project as it continues

The Role of Astrocytic Calcineurin Activation and Downstream Signaling in Neurodegenerative Diseases

Calcineurin (CN) is a calcium (Ca2+)-sensitive serine/threonine protein phosphatase that plays a significant role in several cell signaling pathways, and has been implicated in many neurodegenerative diseases including Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID). Although normally found in neurons, CN also appears at high levels in activated astrocytes under conditions of injury and disease. To elucidate the role of astrocytic calcineurin signaling in neurodegenerative diseases, our lab has used primary rat astrocytes, transgenic and diet-induced mouse models of dementia, and human tissue biospecimens from confirmed AD and VCID cases. To better understand mechanisms for aberrant activation of CN during injury and disease, we created a custom antibody that selectively identifies a proteolyzed, constitutively active CN fragment. Immunolabeling in human biospecimens was done to determine which cell types express high levels of CN proteolysis and hyperactivation. Our results revealed extensive proteolysis of CN in activated astrocytes near pathologic hallmarks of AD (Aβ plaques) and VCID (microinfarcts). When a similar activated CN fragment was expressed in hippocampal astrocytes of healthy adult rats using adeno-associated virus (AAV) vectors, we observed suppressed function of CA3-CA1 excitatory synapses, suggesting that proteolytic activation of CN in astrocytes is a key mechanism for driving neuronal dysfunction in neurodegenerative diseases. To explore the interaction between astrocytic CN and a possible downstream signaling target, we studied the hemichannel-forming protein, connexin43 (Cx43). Previous work has shown that serine 368 near the C terminus of Cx43 is dephosphorylated by CN. Here, we found that dephosphorylation of ser368 was increased in human hippocampal specimens from subjects diagnosed with mild cognitive impairment (MCI). Dephospho-Cx43 levels were correlated, within subject, to elevated levels of CN proteolysis and signaling. Moreover, dephosphorylation of Cx43 could be mimicked in rat primary astrocyte cultures using both exogenous Ca2+ mobilizers (phorbol ester/ionomycin) and endogenous inflammatory mediators (IL-1b), found previously to activate CN in astrocytes. Finally, we created a custom peptide (43Gap52) that encompasses Ser368 and mimics a portion of the C-terminus of Cx43. 43Gap52 prevented IL-1b-mediated dephosphorylation of Cx43, but did not prevent CN-dependent activation of NFAT transcription factors, suggesting that 43Gap52 selectively disrupts CN/Cx43 interactions. Using 43Gap52 and the commercial CN inhibitor cyclosporin A (CsA), we found that blockade of CN/Cx43 interactions reduced hemichannel permeability in primary astrocytes following treatment with IL-1b, suggesting that aberrant CN activation in astrocytes may negatively affect neurons via interactions with Cx43-containing hemichannels. To more clearly understand CN/NFAT signaling in VCID we used a diet-induced model of hyperhomocysteinemia (HHcy) that drives vascular pathology. Using AAV-mediated gene delivery, we injected mice with an astrocyte-targeted inhibitor of CN/NFAT binding (Gfa2-Egfp-VIVIT) or a control virus (Gfa2-Egfp). These mice were further split into two groups, one fed with the HHcy diet and one fed with control diet. Experiments are in progress to assess endpoint measurements including LTP and synaptic strength, RAWM behavior testing, as well as a panel of biochemical measurements

Modeling structure and flexibility of Candida antarctica lipase B in organic solvents

<p>Abstract</p> <p>Background</p> <p>The structure and flexibility of <it>Candida antarctica </it>lipase B in water and five different organic solvent models was investigated using multiple molecular dynamics simulations to describe the effect of solvents on structure and dynamics. Interactions of the solvents with the protein and the distribution of water molecules at the protein surface were examined.</p> <p>Results</p> <p>The simulated structure was independent of the solvent, and had a low deviation from the crystal structure. However, the hydrophilic surface of CALB in non-polar solvents decreased by 10% in comparison to water, while the hydrophobic surface is slightly increased by 1%. There is a large influence on the flexibility depending on the dielectric constant of the solvent, with a high flexibility in water and a low flexibility in organic solvents. With decreasing dielectric constant, the number of surface bound water molecules significantly increased and a spanning water network with an increasing size was formed.</p> <p>Conclusion</p> <p>The reduced flexibility of <it>Candida antarctica </it>lipase B in organic solvents is caused by a spanning water network resulting from less mobile and slowly exchanging water molecules at the protein-surface. The reduced flexibility of <it>Candida antarctica </it>lipase B in organic solvent is not only caused by the interactions between solvent-protein, but mainly by the formation of a spanning water network.</p