In Spring of 2018, I helped collect a 45 cm sediment core from San Blas Basin on the continental shelf of pacific México, 50 km off the coast and north-west of Puerto Vallarta. After noticing that there were large sticks and seeds in the sediment, our Méxican collaborators gifted me the core to analyze lignin, a biomarker for terrestrial organic matter (TOM). Sticks in oceanic mud 50 km off the coast is unusual so we were excited to find out this geological story. I found that the total amount of lignin phenols ranges between 1.5 to 4.5 mg lignin phenol/10 g sediment except for an order of magnitude increase between 18 cm and 26 cm which was 20 to 40 mg lignin phenol/10g sediment. Acid to aldehyde ratios of vanillin-type lignin (Ad/Al (v)), a proxy for degradation, had a range of 0.36 to 0.58 while the section between 18cm to 26cm was fresher with a range of 0.26 to 0.28. S/V to C/V analysis indicated that the lignin is sourced from angiosperms. The section between 18 cm to 26 cm had statistically similar values ranging between S/V of 0.85 to 0.95 and C/V of 0.19 to 0.21. S/V to Ad/Al (v) analysis had a negative slope indicating S-type lignin is preferentially degraded and the background lignin signal could look more like the fresher 18-26 cm section if degradation had not occurred. My lab partners, Méxican collaborators, and I conclude that a large flooding event brought fresh TOM off of the land and the sediment deposition and deposited 8 cm of sediment in one event due to the S/V and C/V values overlapping. The flooding was likely a tsunami, large hurricane, or flash flood from the nearby Santiago river.

People living in rural Northern Tanzania are highly dependent on their natural environment for their health and livelihood. Consequently, they are a vulnerable population with regard to the potential negative effects of climate change. In this study, a semi-structured interview questionnaire was used to interview inhabitants of the Laja, Getamock and Kaza Roho villages, and measure their perception of the effect of climate change on their livelihood, health, and gender roles in the Manyara and Arusha regions of rural Tanzania. A total of 226 interviewees were asked about their perceptions of rainfall patterns, natural resource availability, disease rates, gender roles, and birth control use. The majority of respondents perceived a decrease in the frequency of rainfall and an increase in the frequency of drought. Moreover, 89% of the respondents were determined to be pastoralists or farmers that are directly affected by reduced precipitation, which decreases natural resource availability and crop yield, and increases rates of disease in humans and livestock. Respondents also reported shifts in gender roles to accommodate the rise of health, natural resource, and financial burdens stemming from climate change; for example, men are increasingly responsible for gathering drinking water because sources nearby villages have dried up and only men can drive motorbikes and ox carts now required to travel such long distances. Lastly, it was found that contraception usage has increased in younger, more educated groups in conjunction with a decreased number of desired children. Because family planning are associated with girls achieving higher levels of education and economic growth, improved family planning presents a potential solution to the financial hardship imposed by climate change. Considering the challenge of mitigating the inimical effects of climate change to developed nations, solutions to these problems are critically important to vulnerable groups that are highly dependent on natural resources for their health and livelihood.

Cells use a variety of mechanisms to regulate gene expression. One way cells control gene expression is by forming structures such as DNA loops to position genes in 3D space near regulators. My lab is developing tools to synthetically control 3D genome structure and assess the relationship between positioning and expression. Our strategy is to engineer DNA loops by fusing DNA binding domains to targeting domains that dimerize and bring the two sites together. To ensure the binding domains bind to each other to form a loop, we are developing an allosteric sensor of DNA binding where the dimerization motifs are only active when bound to DNA. Without this switch, the looping interaction would be outcompeted by free binding domains that are not attached to DNA. We used LOCKR, a bioactive protein switch comprised of a protein cage that switches to an ON-state in the presence of a key protein. These proteins are tethered to DNA using dCas9 as a programmable binding domain. I have tested different system parameters, including the length of the linker between dCas9 and the key protein, for increased activation of green fluorescent protein, a reporter gene that is expressed when the switch is activated. My data show that the switch is effective with a variety of linker lengths. I am also exploring other parameters for optimization, such as changing the relative orientation of the dCas9 complexes. Exploring these parameters is important because the switch might be sensitive to small changes in structure or orientation, and we want to identify the optimal arrangement of dCas9 and switch proteins for effective switch function. After this system is optimized, we will be able to direct our efforts toward looping DNA, which will allow us to address broad questions about the relationship between gene position and expression.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by the presence of repetitive patterns of behaviors and deficits in social communication and interaction. Attention to social information is a key component of the development of social communication. Previous studies used eye tracking to examine visual scanning patterns associated with social attention in children with ASD and neurotypical children. Eye tracking is used to both identify the atypical patterns of social attention and to predict clinical outcomes in ASD. Although atypical eye gazing patterns are considered as potential biomarkers, researchers commonly consider data loss in eye tracking as error or noise, and rarely investigate it more thoroughly. In this proposal, we hypothesize that loss of data is a potential signature of core social motivation issue when a social video is playing, and, rather than being a nuisance variable, which reflects the broader continuum of social attentional-motivational challenges faced by individuals with ASD. We used eye tracking to confirm previous findings on atypical attention patterns, and further utilize behavior coding to examine the three types of causes of data loss including blinking, non-compliant behaviors, and technical error. We hypothesize that data loss due to blinking is associated with a lack of social motivation and that data loss due to non-compliant behaviors is associated with executive function. Social motivation and executive function were measured by parent reports. Exploring data loss in eye tracking may help reveal comprehensive and fundamental factors of diminished social motivation and neurocognition in ASD.

The maternal bond is an intimate attachment between a primary caregiver (PC) and their infant which provides the infant with security, facilitating physical, social, and emotional development. A sensitive and responsive environment, such as the presence of healthy maternal bonds, guides an infant’s neurodevelopment. Changes in mood and emotional state can alter the care a PC provides and cause difficulties in bonding with their infant, impacting the baby’s psychological and physical development. In infants, the mechanisms by which development may be impacted are unknown. Recently, research has shown early atypical attention to visual pop-out in autism spectrum disorders. Attention to visual pop-out describes our cognitive ability to quickly identify differing objects presented among similar looking ones. In this project, we investigated whether PC mental health affects attention to visual pop-out in infants. Participants included 50 infants who were assessed at 6 and 12 months of age. PCs completed the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) at both timepoints. Infants watched a 4-minute visual pop-out paradigm, which included social (face) and non-social (shape) trials. We assessed responses to visual pop-outs and explored whether BDI and BAI scores correlated with visual pop-out performance at 6 and 12 months. We also investigated whether BDI and BAI scores influenced the development of attention to visual pop-out between 6 and 12 months. We hypothesized infants of primary caregivers who report more (a) depressive and (b) anxious symptoms will demonstrate weaker identification of the pop-out during social trials compared to their peers but be unaffected during nonsocial trials. This study will help deepen our understanding of the impact of maternal depression and anxiety on infant development and help health providers identify and support families.

Immunological memory prevents reinfection by a pathogen. This protection is accomplished by memory T cells expressing T cell receptors (TCR) specific for previously encountered pathogen-derived peptides (antigens). Conventionally, memory T cells are thought to be inert during novel infections because there is no interaction between their TCRs with their specific antigens. Despite this, we and others have demonstrated that these T cells (here termed “bystanders”) can be activated by inflammatory signals alone and gain cytotoxic effector function in the absence of TCR-antigen interaction. This study aims to determine how inflammation regulates and attenuates bystander responses and how we can leverage these cells therapeutically. Using in vitro cell stimulations, we found that the inhibitory receptor, programmed cell death protein 1 (PD-1), is strongly upregulated by bystanders after exposure to certain inflammatory cytokines. This finding is unique because the current paradigm is that PD-1 expression is caused by TCR stimulation and PD-1 represents a target to manipulate bystander responses. Further, in mouse models of vaccination, we found that bystander-mediated killing can limit vaccine antigen. We believe that interfering with bystander T cell effector functionality could be targeted to improve antigen-specific vaccine responses. Through understanding the mechanisms that dictate bystander function, we may better modulate bystander T cells function during infection, vaccination, and cancer to improve patient outcomes.

In the US, the number of children with obesity has reached a staggering 13.7 million. Though there are diets to assist weight loss, recent research suggests a neurobiological basis of obesity specifically related to the mediobasal hypothalamus (MBH), a critical brain structure involved in energy homeostasis, metabolism, and appetite. However, proliferation of hypothalamic gliosis, a cellular inflammatory response, disrupts the function and is shown, in rodents, as a key component in diet-induced obesity. Further conclusions reveal that highly caloric and high-fat diets, in rodents, can cause MBH gliosis. This project seeks to investigate the relationship between diet and hypothalamic gliosis in children, the latter assessed by magnetic resonance imaging (MRI). We expect children with an unhealthy diet to have an increased BMI z-score and greater evidence of MBH gliosis. Participants (N=192) were recruited as part of the longitudinal NIH Adolescent Brain Cognitive Development study. Anthropometric and demographic data were collected along with brain MRI T2-weighted images at the baseline visit. MBH gliosis was measured by using the signal ratio for T2 intensity of the mean bilateral MBH/Amygdala signal ratio; Putamen/Amygdala was used as control ratio. At the one year follow-up, the child’s habitual diet in the past year was assessed using a parent-report food frequency questionnaire. Higher total points represented a healthier overall diet. Additionally, follow-up anthropometric data was obtained to determine the child’s adiposity change over time. At baseline, mean age was 9.9±0.6 and 49% were males. Mean BMI z-score was 0.76±1.05, 19% were overweight and 23% with obesity. Preliminary results in a subset of participants (N=60) revealed a trend for an association between an unhealthy diet and evidence of MBH gliosis (t=1.59, P=0.117). By emphasizing the neurobiological basis of obesity, potential insights can inform targeted diet-related treatments of childhood obesity; thus, furthering the understanding of child obesity pathogenesis.

Children have more exposure to screen media today than any other generation. In the U.S., rates of obesity in children have also tripled in 4 decades. A disruption in the brain called gliosis has been described to participate in obesity pathophysiology if it occurs in a brain region important for energy balance, called the mediobasal hypothalamus (MBH). The objective of this study is to explore possible relationships between MBH gliosis and parents’ reports on screen time their child engages in. This study will also look into variables that may mediate these relationships, such as body adiposity and impulsivity. I hypothesize that there will be a positive correlation between screen media use and MBH gliosis with obesity and the level of impulsivity being positively correlated to both gliosis and screen time. The methodology consists of data from participants (N = 192) in the NIH Adolescent Brain Cognitive Development study. The NIH Toolbox Flanker Inhibitory Control and Attention Test was used to measure child’s impulsivity, and the parents were given the Screen time report to measure the average daily screen media time of each child. Along with these measures, participant’s age, sex, race, BMI z-score, waist/height ratio, and T2-weighted MRI will be included. MBH gliosis will be measured by T2 MRI signal intensity (brightness) of the mean bilateral MBH/Amygdala signal ratio; Putamen/Amygdala will be used as control ratio. Participants were 51% female with an average age of 9.9±0.63 years. Within our sample, 57.3%, 19.3%, and 23.4% of subjects were considered healthy weight, overweight, and with obesity, respectively. Anthropometric and behavioral data recorded on average 11.2 months after the initial tests will be included to calculate changes over time. This research will help to further illuminate the relationships between screen time and obesity, and will potentially be helpful in proposing new treatments for children with obesity.