Doctor of Philosophy

dissertationThe human brain is the seat of cognition and behavior. Understanding the brain mechanistically is essential for appreciating its linkages with cognitive processes and behavioral outcomes in humans. Mechanisms of brain function categorically represent rich and widely under-investigated biological substrates for neural-driven studies of psychiatry and mental health. Research examining intrinsic connectivity patterns across whole brain systems utilizes functional magnetic resonance imaging (fMRI) to trace spontaneous fluctuations in blood oxygen-level dependent (BOLD) signals. In the first study presented, we reveal patterns of dynamic attractors in resting state functional connectivity data corresponding to well-documented biological networks. We introduce a novel simulation for whole brain dynamics that can be adapted to either group-level analysis or single-subject level models. We describe stability of intrinsic functional architecture in terms of transient and global steady states resembling biological networks. In the second study, we demonstrate plasticity in functional connectivity following a minimum six-week intervention to train cognitive performance in a speed reading task. Long-term modulation of connectivity with language regions indicate functional connectivity as a candidate biomarker for tracking and measuring functional changes in neural systems as outcomes of cognitive training. The third study demonstrates utility of functional biomarkers in predicting individual differences in behavioral and cognitive features. We successfully predict three major domains of personality psychologyintelligence, agreeableness, and conscientiousnessin individual subjects using a large (N=475) open source data sample compiled by the National Institutes of Healths Human Connectome Project

Topic-dependent sentiment analysis of financial blogs

While most work in sentiment analysis in the financial domain has focused on the use of content from traditional finance news, in this work we concentrate on more subjective sources of information, blogs. We aim to automatically determine the sentiment of financial bloggers towards companies and their stocks. To do this we develop a corpus of financial blogs, annotated with polarity of sentiment with respect to a number of companies. We conduct an analysis of the annotated corpus, from which we show there is a significant level of topic shift within this collection, and also illustrate the difficulty that human annotators have when annotating certain sentiment categories. To deal with the problem of topic shift within blog articles, we propose text extraction techniques to create topic-specific sub-documents, which we use to train a sentiment classifier. We show that such approaches provide a substantial improvement over full documentclassification and that word-based approaches perform better than sentence-based or paragraph-based approaches

Exploring the use of paragraph-level annotations for sentiment analysis of financial blogs

In this paper we describe our work in the area of topic-based sentiment analysis in the domain of financial blogs. We explore the use of paragraph-level and document-level annotations, examining how additional information from paragraph-level annotations can be used to increase the accuracy of document-level sentiment classification. We acknowledge the additional effort required to provide these paragraph-level annotations, and so we compare these findings against an automatic means of generating topic-specific sub-documents

AMPA Receptor Phosphorylation and Synaptic Colocalization on Motor Neurons Drive Maladaptive Plasticity below Complete Spinal Cord Injury.

Clinical spinal cord injury (SCI) is accompanied by comorbid peripheral injury in 47% of patients. Human and animal modeling data have shown that painful peripheral injuries undermine long-term recovery of locomotion through unknown mechanisms. Peripheral nociceptive stimuli induce maladaptive synaptic plasticity in dorsal horn sensory systems through AMPA receptor (AMPAR) phosphorylation and trafficking to synapses. Here we test whether ventral horn motor neurons in rats demonstrate similar experience-dependent maladaptive plasticity below a complete SCI in vivo. Quantitative biochemistry demonstrated that intermittent nociceptive stimulation (INS) rapidly and selectively increases AMPAR subunit GluA1 serine 831 phosphorylation and localization to synapses in the injured spinal cord, while reducing synaptic GluA2. These changes predict motor dysfunction in the absence of cell death signaling, suggesting an opportunity for therapeutic reversal. Automated confocal time-course analysis of lumbar ventral horn motor neurons confirmed a time-dependent increase in synaptic GluA1 with concurrent decrease in synaptic GluA2. Optical fractionation of neuronal plasma membranes revealed GluA2 removal from extrasynaptic sites on motor neurons early after INS followed by removal from synapses 2 h later. As GluA2-lacking AMPARs are canonical calcium-permeable AMPARs (CP-AMPARs), their stimulus- and time-dependent insertion provides a therapeutic target for limiting calcium-dependent dynamic maladaptive plasticity after SCI. Confirming this, a selective CP-AMPAR antagonist protected against INS-induced maladaptive spinal plasticity, restoring adaptive motor responses on a sensorimotor spinal training task. These findings highlight the critical involvement of AMPARs in experience-dependent spinal cord plasticity after injury and provide a pharmacologically targetable synaptic mechanism by which early postinjury experience shapes motor plasticity

The Leishmania donovani Ortholog of the Glycosylphosphatidylinositol Anchor Biosynthesis Cofactor PBN1 Is Essential for Host Infection

Visceral leishmaniasis is a deadly infectious disease caused by Leishmania donovani, a kinetoplastid parasite for which no licensed vaccine is available. To identify potential vaccine candidates, we systematically identified genes encoding putative cell surface and secreted proteins essential for parasite viability and host infection. We identified a protein encoded by LdBPK_061160 which, when ablated, resulted in a remarkable increase in parasite adhesion to tissue culture flasks. Here, we show that this phenotype is caused by the loss of glycosylphosphatidylinositol (GPI)-anchored surface molecules and that LdBPK_061160 encodes a noncatalytic component of the L. donovani GPI-mannosyltransferase I (GPI-MT I) complex. GPI-anchored surface molecules were rescued in the LdBPK_061160 mutant by the ectopic expression of both human genes PIG-X and PIG-M, but neither gene could complement the phenotype alone. From further sequence comparisons, we conclude that LdBPK_061160 is the functional orthologue of yeast PBN1 and mammalian PIG-X, which encode the noncatalytic subunits of their respective GPI-MT I complexes, and we assign LdBPK_061160 as LdPBN1. The LdPBN1 mutants could not establish a visceral infection in mice, a phenotype that was rescued by constitutive expression of LdPBN1. Although mice infected with the null mutant did not develop an infection, exposure to these parasites provided significant protection against subsequent infection with a virulent strain. In summary, we have identified the orthologue of the PBN1/PIG-X noncatalytic subunit of GPI-MT I in trypanosomatids, shown that it is essential for infection in a murine model of visceral leishmaniasis, and demonstrated that the LdPBN1 mutant shows promise for the development of an attenuated live vaccine

S22RS SGR No. 24 (Carceral Labor)

A Resolution To urge and request Louisiana State University to issue an official public statement regarding their plans for carceral labor to not return to the A&M Campu

Developmental stage of oligodendrocytes determines their response to activated microglia in vitro

<p>Abstract</p> <p>Background</p> <p>Oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ.</p> <p>Methods</p> <p>OPCs and microglia were isolated from rat cortex. OPCs were induced to differentiate into oligodendrocytes with thyroid hormone in defined medium. For selected experiments, microglia were added to OPC or oligodendrocyte cultures. Lipopolysaccharide was used to activate microglia and microglial activation was confirmed by TNFα ELISA. Cell survival was assessed with immunocytochemistry and cell counts. OPC proliferation and oligodendrocyte apoptosis were also assessed.</p> <p>Results</p> <p>OPCs and oligodendrocytes displayed phenotypes representative of immature and mature oligodendrocytes, respectively. Activated microglia reduced OPC survival, but increased survival and reduced apoptosis of mature oligodendrocytes. Activated microglia also underwent cell death themselves.</p> <p>Conclusion</p> <p>Activated microglia may have divergent effects on OPCs and mature oligodendrocytes, reducing OPC survival and increasing mature oligodendrocyte survival. This may be of importance because activated microglia are present in several disease states where both OPCs and mature oligodendrocytes are also reacting to injury. Activated microglia may simultaneously have deleterious and helpful effects on different cells after central nervous system injury.</p

Computer Science for Muncie (and Surrounding) Schools (CS4MS+) - Spring 2021

Partnering with local schools, the Computer Science for Muncie (and Surrounding) Schools (CS4MS+) project team researched, developed, curated, and delivered instructional resources which incorporate Computer Science (CS) into educational offerings, with a focus on the Indiana CS academic standards, and worked to advance teachers’ understanding of CS and/or interacted with their students as a teaching assistant. Although CS student focused, an interdisciplinary project team was sought, with another project focus being to expose underrepresented minorities and females to CS. When Indiana introduced CS into their academic standards, CS4MS+ was created to support local teachers in this endeavor. To learn more, please click on the "Computer Science for Muncie (and Surrounding) Schools (CS4MS+)" title above, then use the links provided to the right when the new page appears

A Novel Method for Assessing Proximal and Distal Forelimb Function in the Rat: the Irvine, Beatties and Bresnahan (IBB) Forelimb Scale

Several experimental models of cervical spinal cord injury (SCI) have been developed recently to assess the consequences of damage to this level of the spinal cord (Pearse et al., 2005, Gensel et al., 2006, Anderson et al., 2009), as the majority of human SCI occur here (Young, 2010; www.sci-info-pages.com). Behavioral deficits include loss of forelimb function due to damage to the white matter affecting both descending motor and ascending sensory systems, and to the gray matter containing the segmental circuitry for processing sensory input and motor output for the forelimb. Additionally, a key priority for human patients with cervical SCI is restoration of hand/arm function (Anderson, 2004). Thus, outcome measures that assess both proximal and distal forelimb function are needed. Although there are several behavioral assays that are sensitive to different aspects of forelimb recovery in experimental models of cervical SCI (Girgis et al., 2007, Gensel et al., 2006, Ballerman et al., 2001, Metz and Whishaw, 2000, Bertelli and Mira, 1993, Montoya et al., 1991, Whishaw and Pellis, 1990), few techniques provide detailed information on the recovery of fine motor control and digit movement