Mechanistic and Physiological Studies of the Insulin-Dependent Regulation of FOXA2

The Forkhead box A2 transcription factor (Foxa2/HNF-3β) has been shown to be a key regulator of genes involved in the maintenance of glucose and lipid homeostasis in the liver, and is constitutively inactivated in several hyperinsulinemic/obese mouse models, thereby enhancing their metabolic phenotypes. Foxa2 is activated under fasting conditions, but is inhibited by insulin signaling via PI3K/Akt in a phosphorylation-dependent manner, which results in its nuclear exclusion. However, the mechanism and relative importance of nuclear export have not yet been elucidated. In addition, the existence and potential role of insulin-dependent regulation of Foxa2 have not been studied in other tissues where it is expressed, such as the gut, lung, and hypothalamus. Here we further investigate the regulation of Foxa2 by insulin and the mechanism and relevance of its nuclear exclusion. We demonstrate that differential regulation of Foxa2 exists in different mouse models, that this variability is dependent on circulating insulin levels, and that Foxa2 activity correlates with metabolic function. We further show that Foxa2 contains a functional nuclear export signal and is excluded from the nucleus via a CRM1- dependent pathway in response to insulin signaling. Our data provide direct evidence that nuclear export-defective Foxa2 is phosphorylated and inactivated by insulin both in vitro and in vivo, suggesting that phosphorylation itself is the main regulatory event regulating the activity of Foxa2, and not nuclear exclusion per se. Finally, we provide evidence for and physiological consequences of insulin-dependent inactivation of Foxa2 in two other metabolic organs: the hypothalamus and the lung

Examining the Association between Parental Smoking and Adolescent Age of Smoking Initiation in Africa

Tobacco use is responsible for millions of preventable illnesses and deaths throughout the world. Nevertheless, multitudes of people begin smoking every day, most before reaching the age of 18. Previous research suggests that parental smoking status is a significant predictor of adolescent smoking. Furthermore, parental smoking status may also be associated with a younger age of smoking initiation, which increases a person’s risk of nicotine dependence, cancer, and death. This study examines the association between parental smoking and adolescent age of smoking initiation in 14 African countries. Data for this study was obtained from the Global Youth Tobacco Survey from 2003 – present. Parental smoking status was significantly associated with a younger age of adolescent smoking initiation; maternal smoking had a greater influence than paternal smoking. Gender was also significantly associated with age of initiation; girls are smoking at a younger age than boys. In addition, parental smoking was significantly associated with current smoking among adolescents. The tobacco industry is increasingly targeting these countries to market products to women and adolescents, among whom smoking prevalence is currently low. More rigorous examinations of the association between parent and adolescent smoking in developing countries are needed. Immediate and compelling interventions in the areas of education for parents and adolescents on the health consequences of smoking, access to cessation benefits, and policies to reduce the visibility of smoking are critical steps to preventing tobacco-related death and disease

Shorebird Staging and Migratory Movements at Chaplin and Reed Lakes, Saskatchewan, with Implications for Wind Energy Development

Increasing knowledge of long distance shorebird (order Charadriiformes) migrations may elucidate causes of shorebird declines and direct management within migratory routes. Migrating birds rely on staging sites, areas with reliably high food abundance, for rest and refueling. Stressors at these sites could have population level impacts and post-migration carry-over effects. My thesis research examined staging bird abundance and migratory movements to and from Chaplin and Reed Lakes, Saskatchewan, a major staging site of hemispheric importance in the Central Flyway used by over 100,000 shorebirds each year. My objectives were to 1) examine time of peak abundance by multiple migratory shorebird species using Chaplin and Reed Lakes during spring and fall migration, as well as estimate spring stopover duration and population size of Sanderling (Calidris alba) and 2) investigate movement patterns of migratory shorebirds as they arrive at and depart from Chaplin and Reed Lakes, and determine the extrinsic factors influencing observed flight patterns to inform risk from current and future wind energy developments. I used a combination of point count surveys and radio telemetry data to meet my objectives. Staging, arctic-breeding species at Chaplin and Reed Lakes were counted weekly during spring northward (2014 – 2017) and fall southward (2016 – 2017) migration by conducting point count surveys to examine temporal patterns and estimate population size. Detailed assessments of my focal species, Sanderling included capture, banding and radio-tagging in the Gulf of Mexico and at Chaplin Lake (2015-2017) to track their migratory movements and stopover duration in relation to weather and time of day variables using automated radio telemetry. Spring migration involved larger numbers of species (including species at risk), larger numbers of individuals, and more concentrated timing among years than fall migration. Sanderlings staged for a mean of 11.1 (95% CI = 8.59 –13.6) days and population size averaged ~75,000 birds, with estimates ranging from ~56,000 to ~91,000 among years. Population estimates were seven to 17 times larger than raw peak abundance counts, demonstrating the need to account for stopover duration in population estimates. Chaplin and Reed Lakes departures, but not arrivals, were significantly influenced by time and weather. Sanderlings were more likely to depart at sunset or sunrise when winds were blowing towards the northwest at intermediate speeds and less likely to depart when winds were blowing towards the southeast at high speeds. Knowledge of when large numbers of birds are using the area and what environmental conditions are associated with migratory movements can be used to identify where and when birds are at the greatest risks of collision with wind energy turbines. My results have implications for shorebird conservation at Chaplin and Reed Lakes and other staging sites in the Central flyway, and my thesis provides recommendations for management and mitigation of threats from current and future wind energy developments

Influential Article Review- Issues Surrounding Immigration and Crime in Arizona

This paper examines immigration. We present insights from a highly influential paper. Here are the highlights from this paper: Using newly released detailed data on all prisoners who entered the Arizona state prison from January 1985 through June 2017, we are able to separate non-U.S. citizens by whether they are illegal or legal residents. Unlike other studies, these data do not rely on self-reporting of criminal backgrounds. Undocumented immigrants are at least 142% more likely to be convicted of a crime than other Arizonans. They also tend to commit more serious crimes and serve 10.5% longer sentences, more likely to be classified as dangerous, and 45% more likely to be gang members than U.S. citizens. Yet, there are several reasons that these numbers are likely to underestimate the share of crime committed by undocumented immigrants. There are dramatic differences between in the criminal histories of convicts who are U.S. citizens and undocumented immigrants. Young convicts are especially likely to be undocumented immigrants. While undocumented immigrants from 15 to 35 years of age make up slightly over two percent of the Arizona population, they make up about eight percent of the prison population. Even after adjusting for the fact that young people commit crime at higher rates, young undocumented immigrants commit crime at twice the rate of young U.S. citizens. These undocumented immigrants also tend to commit more serious crimes. If undocumented immigrants committed crime nationally as they do in Arizona, in 2016 they would have been responsible for over 1,000 more murders, 5,200 rapes, 8,900 robberies, 25,300 aggravated assaults, and 26,900 burglaries. For our overseas readers, we then present the insights from this paper in Spanish, French, Portuguese, and German

From Puppy Love to Pet Peeve: What Causes Second/Successor Dog Syndrome in Assistance-Dog Handlers and Companion-Dog Owners?

In a Guide Dog population, there is a higher return rate of handlers’ second dog compared with any prior or subsequent dog pairings. This phenomenon is called Second Dog Syndrome (SDS). Qualitative studies have identified defining features of this syndrome in Guide Dog handlers; however, there has been no peer-reviewed study into the experience of SDS in companion-dog owners or handlers of other assistance dogs. As such, this exploratory study aimed to define the SDS experience in companion-dog owners and assistance-dog handlers. Ten participants, all women, were recruited to participate in focus groups for companion-dog owners (n = 5) and assistance-dog handlers (n = 5). Transcripts were analyzed using thematic analysis. SDS was characterized by a strong bond with the previous dog, ongoing bereavement related to the previous dog loss, negative emotions related to the successor dog, and inability to bond with them. This appeared to be due to comparisons made between the successor and previous dog and unmet expectations of the new dog. For companion-dog owners it was also characterized by a fear of getting hurt again; for assistance-dog owners it was an inability to trust the successor dog, differences in work ability, and a threat to their independence. Time since the loss of the previous dog, awareness of the phenomenon of SDS, and support from the community also influenced the SDS experience. One unexpected finding was that SDS was not exclusively linked to second-paired dogs and that it may be more aptly named “Successor Dog Syndrome.” Given that poor outcomes associated with unsuccessful dog–owner bonding may result in relinquishment, this study provides an important first step to being able to quantify the experience of SDS to develop interventions in the future

A study into the relationship between dental development and cervical vertebral maturation in UK subjects

Aim: To examine relationships between dental and skeletal maturity in White British and Asian UK subjects. Methods: Ninety subjects per ethnic group, with digital panoramic and lateral cephalometric radiographs, were selected from the records of Birmingham Dental Hospital. Dental maturity was assessed from the development stage of the left mandibular canine, first and second premolar, and second molar using the Demirjian Index (DI). Skeletal maturity was determined from cervical vertebral maturation (CVM) stage using the method of Baccetti. Spearman rank-order correlation coefficients were calculated to measure the association between DI and CVM. Results: Females reached each CVM stage at an earlier age than males. There was no statistically significant difference in the mean age of White British and Asian subjects at each CVM stage. The mandibular canine had the highest correlation with CVM stage in White British males (r = 0.568). The mandibular second molar demonstrated the highest correlation to CVM stage in White British females and in Asian males and females (r = 0.533; r = 0.752; r = 0.569 respectively). Conclusion: Moderate statistically significant correlations were observed between DI and CVM stages, suggesting that dental development stage can be considered as a method for determining skeletal maturity in UK subjects during orthodontic treatment planning