The causative agent of malaria, Plasmodium spp., generated 608,000 deaths worldwide in 2022 according to the World Health Organization and disproportionately threatens endemic areas of Africa. Plasmodium sporozoites infect the host by entering the bloodstream through the skin following bites by female Anopheles mosquitoes. From there, sporozoites migrate to the liver and infect hepatocytes. A single sporozoite-infected hepatocyte is capable of producing thousands of merozoites, which go on to enter the bloodstream. Complete elimination of infected hepatocytes is necessary to achieve sterile protection. In order to observe adaptive and innate immune cell localization towards infected hepatocytes, we applied fluorescence microscopy on livers in a BALB/c rodent model of malaria. Naïve unvaccinated mice were infected with sporozoites of Plasmodium yoelii, a rodent malaria parasite. Two important cell populations are recruited to infected hepatocytes. The first are tissue resident memory CD8+ T cells (Trm), which are crucial in pre-erythrocytic protection. The second are Kupffer cells, which are specialized liver macrophages. To measure these adaptive and innate cell populations, respectively, we applied fluorescently-labeled antibodies to mark the parasite as well as Trms and Kupffer cells. After staining the collected liver tissue and imaging with a widefield fluorescent microscope, we visualized recruitment and measured immune cell proximity quantitatively within a region of interest of the area surrounding infected hepatocytes using microscopy imaging analysis software. This method will be used to test the hypothesis that Trms and Kupffer cells are induced following sporozoite challenge in the rodent malaria model.

Western U.S. wildfires are a growing threat to human lives, societal infrastructure, and global climate. While it is well known that meteorological factors impact wildfire intensity and growth rate, quantitative relationships between meteorology and wildfire are scale-dependent. For example, a recent study evaluating all recently observed California wildfires found that explosive fire growth was strongly related to short periods of strong winds and dryness. However, that study used data from a global atmospheric reanalysis (which cannot resolve local winds). As such, even the strong relationships found between meteorology and wildfire growth may have been underestimated. Given the potential consequences involved in predicting and mitigating future wildfires, it is important to understand the real-world accuracy of previously determined fire-environment relationships. To do so, this project compares how local meteorological observations from Remote Automated Weather Stations (RAWS) differ from reanalysis observations during known wildfires. The seasonal and spatial variation in the different relationships is also evaluated. Analysis has shown that the RAWS network is dense enough to adequately represent conditions at each fire being examined. Early results indicate that RAWS and reanalyses have similarly timed wind events during the max growth period. These results are promising, as they indicate that global atmospheric reanalyses can be used as a proxy for ground observations in remote terrain when analyzing periods of extreme wildfire growth.

Spasticity is an increase in muscle tone (hypertonus) and abnormal muscle stiffness that impedes functional activity. Oftentimes observed among individuals with chronic neurological conditions such as traumatic brain or spinal cord injury (SCI), spasticity develops as a result of damage to the central nervous system (CNS). This damage disrupts the balance of supraspinal inhibitory and excitatory inputs to the spinal cord, which can lead to the loss of inhibitory inputs and hyperexcitation of the spinal reflex arc. The aim of this project is to develop an electrical stimulation protocol that regulates imbalances of supraspinal input and the spinal reflex in order to potentially alleviate spasticity caused by traumatic neural injury in patients. The hyperexcitation associated with spasticity is measured using the Hoffman-reflex (H-reflex). Previous studies have revealed that electrical stimulation of the rat motor cortex can modulate long-term spinal excitability. In this study, behaving noninjured Long Evans rats are implanted with cortical implants to induce stimulation to the motor cortex, grounding electrodes to filter environmental noise, cuff electrodes to evoke the H-reflex, and EMG electrodes to record the H-reflex response. The H-reflex is assessed by stimulating a cuff electrode surrounding the median nerve and measuring the consequent activity of EMG electrodes that are implanted into the flexor, extensor, and tricep muscles before and after electrical stimulation of the motor cortex. Our preliminary results indicate that different frequencies of cortical stimulation can modulate the H-reflex, suggesting that our novel cortical stimulation protocol may reduce spasticity and promote restoration of motor function. In future studies, I plan to assess the efficacy of cortical stimulation for improving spinal excitability in spastic animals following chronic SCI.

Spinal cord injury (SCI) causes physical disability and chronic pain, but there can also be psychological issues like depression and/or anxiety. Clinically, the estimated rates of depression among the SCI population are from 11% to 37%, according to UW Medicine. In rodents, after SCI, both males and females demonstrated anxiety-like behavior, and female mice became more anxious while male rats became more hypersensitive to thermal stimuli. These findings highlight the complexity of the systematic changes after SCI, all of which may impact the quality of life and limit functional recovery. We have found a sex difference in the effectiveness of electrical stimulation in promoting functional recovery after cervical SCI. In our experiment, females show robust functional improvements with activity-dependent spinal stimulation. The current study aims to investigate the role of affective behaviors (depression and anxiety) and pain after SCI on functional recovery in male and female rats. Before injury, all rats will undergo baseline assessments to establish behavioral norms, which involve training and evaluations designed to measure motor ability, emotional state, and sensitivity to various stimulations. Three weeks after SCI, rats will be assessed with the same battery of tests and then start daily treatment of drugs that can modulate emotional states and relieve pain, including a mixed serotonin and norepinephrine reuptake inhibitor, duloxetine (or no drug control), for five weeks. Behavioral assays will be repeated at the end of the treatment period, and tissue will be collected for histological analysis. I will primarily be responsible for conducting and analyzing an assay of anxiety-like behaviors, the open field test, and the assay of depression-like behaviors, the sucrose splash test. We expect to understand better the relationship between affective responses and motor function post-SCI, and the potential therapeutic benefits of antidepressant treatments, and particularly identify sex differences that may limit recovery.