Landscape genetics reveal broad and fine‐scale population structure due to landscape features and climate history in the northern leopard frog (Rana pipiens) in North Dakota

Prehistoric climate and landscape features play large roles structuring wildlife populations. The amphibians of the northern Great Plains of North America present an opportunity to investigate how these factors affect colonization, migration, and current population genetic structure. This study used 11 microsatellite loci to genotype 1,230 northern leopard frogs (Rana pipiens) from 41 wetlands (30 samples/wetland) across North Dakota. Genetic structure of the sampled frogs was evaluated using Bayesian and multivariate clustering methods. All analyses produced concordant results, identifying a major east–west split between two R. pipiens population clusters separated by the Missouri River. Substructuring within the two major identified population clusters was also found. Spatial principal component analysis (sPCA) and variance partitioning analysis identified distance, river basins, and the Missouri River as the most important landscape factors differentiating R. pipiens populations across the state. Bayesian reconstruction of coalescence times suggested the major east– west split occurred ~13–18 kya during a period of glacial retreat in the northern Great Plains and substructuring largely occurred ~5–11 kya during a period of extreme drought cycles. A range‐wide species distribution model (SDM) for R. pipiens was developed and applied to prehistoric climate conditions during the Last Glacial Maximum (21 kya) and the mid‐Holocene (6 kya) from the CCSM4 climate model to identify potential refugia. The SDM indicated potential refugia existed in South Dakota or further south in Nebraska. The ancestral populations of R. pipiens in North Dakota may have inhabited these refugia, but more sampling outside the state is needed to reconstruct the route of colonization. Using microsatellite genotype data, this study determined that colonization from glacial refugia, drought dynamics in the northern Great Plains, and major rivers acting as barriers to gene flow were the defining forces shaping the regional population structure of R. pipiens in North Dakota

Essays on Public Policy

The first chapter examines the impact of Red Flag Laws on homicide rates and suicide rates. Red Flag Laws seek to implement gun control measures by allowing the removal of firearms from individuals who pose a danger to themselves or others. Using a two-way fixed effects (TWFE) difference-in-differences (DiD) estimations, I demonstrate a negative and plausibly causal relationship between a state implementing a Red Flag Law and homicide rates. While there is also a reduction in suicide rates, I am unable to make causal claims. This study is the first to empirically examine Red Flag Laws, with an eye towards casual inference. These effects are primarily driven by states that permit both family members and law enforcement to petition a state court for the removal of firearms. The second chapter adds to the existing literature on capital punishment. However, I focus on state-level execution moratoriums and their impact on homicide rates. Currently, there are five states with such moratoriums: Oregon (since 2011), Colorado (since 2013; the death penalty was abolished in 2020), Washington (since 2014; the death penalty was abolished in 2018), Pennsylvania (since 2015), and California (since 2019). Using the synthetic control method (SCM) I fail to find a statistical significance on homicide rates for the states who adopt such a policy. Robustness checks and supplementary analyses were conducted to ensure the validity of the primary SCM results. Furthermore, additional analyses incorporating control variables, such as population, race, income, and unemployment rate, were performed using a two-way fixed effects (TWFE) difference-in-differences (DiD) model. The findings consistently show no statistically significant effect of the policy on homicide rates. The third chapter is joint work with Dr. Bryan McCannon. In it, we exploit a novel Covid-19 policy where the state of California mandated a state-wide zero dollar bail for all misdemeanor and non-violent felony offenses. This policy was in affect for three months, from April 2020 through June 2020. After the state-wide mandate was lifted, individual counties were able to continue the zero dollar bail policy or revert back to pre-Covid bail schedules. We investigate whether the elimination of cash bail promotes crime. Our empirical evidence suggests that this policy had a statistical significant impact on violent crimes, specifically assaults. Property crime results tend to unreliable, depending on the specification used. We further show that it did not affect law enforcement’s clearance rate and, therefore, is likely to be a direct effect from eroding deterrence. Using a leave-one-out process, which allows us to assess how sensitive our result is to crime and policy in any one particular jurisdiction. Doing so, we find little difference in the coefficient estimate. Each of the 58 regressions produces an estimated effect that positive and statistically different from zero at the 5% level

Prolactin Drives a Dynamic STAT5A/HDAC6/HMGN2 Cis-Regulatory Landscape Exploitable in ER+ Breast Cancer

The hormone prolactin has been implicated in breast cancer pathogenesis and regulates chromatin engagement by the transcription factor, STAT5A. STAT5A is known to inducibly bind promoters and cis-regulatory elements genome-wide, though the mechanisms by which it exerts specificity and regulation of target gene expression remain enigmatic. We previously identified HDAC6 and HMGN2 as cofactors that facilitate prolactin induced, STAT5A mediated gene expression. Here, multi-condition STAT5A, HDAC6, and HMGN2 ChIP-seq with parallel condition RNA-seq are utilized to reveal the cis-regulatory landscape and cofactor dynamics underlying prolactin stimulated gene expression in breast cancer. We find that prolactin regulated genes are significantly enriched for cis-regulatory elements bound by HDAC6 and HMGN2, and that inducible STAT5A binding at enhancers, rather than promoters, conveys specificity for prolactin regulated genes. The selective HDAC6 inhibitor, ACY-241, blocks prolactin induced STAT5A chromatin engagement at cis-regulatory elements as well as a significant proportion of prolactin stimulated gene expression. We identify functional pathways known to contribute to the development and/or progression of breast cancer that are activated by prolactin and inhibited by ACY-241. Additionally, we find that the DNA sequences underlying shared STAT5A and HDAC6 binding sites at enhancers are differentially enriched for estrogen response elements (ESR1 and ESR2 motifs) relative to enhancers bound by STAT5A alone. Gene set enrichment analysis identifies significant overlap of ERα regulated genes with genes regulated by prolactin, particularly prolactin regulated genes with promoters or enhancers co-occupied by both STAT5A and HDAC6. Lastly, the therapeutic efficacy of ACY-241 is demonstrated in in vitro and in vivo breast cancer models, where we identify synergistic ACY-241 drug combinations and observe differential sensitivity of ER+ models relative to ER- models

An Investigation of Hindsight Bias in Nascent Venture Activity

We posit that individuals who are actively engaged in activities to develop their own venture will exhibit hindsight bias when recalling their startup experiences. We observe that those who fail to develop their startup activity into an operating business demonstrate substantial hindsight bias concerning the probability of venture formation. In particular, the recalled probability of success, reported after their decision to quit, is lower than the probability of success solicited during the nascent process. We argue that the systematic distortion of the past has important implications for individuals involved in the venturing process. Specifically, we suggest that these individuals are at risk of overestimating their chances of success when starting future nascent activity if they do not correct for their optimistic tendencies. The evidence from this study suggests it is important to recognize that what nascent entrepreneurs believe they experienced, and what they actually experienced, may not be equivalent