Doctor of Philosophy

dissertationThe PIE series of D-peptide HIV entry inhibitors, PIE12-trimer and Chol-PIE12-trimer (CPT31), inhibit a wide range of HIV isolates with pM potency while also exhibiting a high barrier to resistance. Here, we show that HIV acquires a primary PIE12 resistance mutation (Q577R/N/K) in both in vitro and in vivo resistance models. Development of this resistance mutation comes at a significant fitness cost to the virus, but the virus also acquires a set of compensatory mutations that rescue this fitness defect. We also show that CPT31 is an effective therapeutic against SHIV infection in rhesus macaques in both treatment and preventative contexts. These data indicate that CPT31 is a promising clinical candidate and could provide a novel agent with a unique mechanism of action against HIV

Patterns of Genomic Introgression in Topminnow Hybrid Zones

Hybridization and introgression are two important evolutionary mechanisms that can increase genetic diversity. Interesting introgression patterns can form when parental species have genes that confer some adaptive benefit to the organism. The Fundulus notatus species complex contains species with various identifying characterisics. Fundulus notatus, the blackstripe topminnow, and Fundulus olivaceus, the blackspotted topminnow, are closely related and occupy many of the same rivers in their preferred niches. These two species often hybridize and form hybrid zones where their niches overlap. We studied two hybrid zones located in the Tombigbee River and Spring River. Within each hybrid zone, we performed a structure analysis to identify parental species and those of mixed ancestry. We then performed a sliding window analysis to analyze the hybrid genomes present in each hybrid zone. When comparing the two hybrid zones, we identified overlapping regions of low introgression on five chromosomes, whereas we only found one overlapping region of high introgression. We then identified putative functions of genes present within these regions, and most genes in the regions of low introgression had functions in the categories of cell development, intra/intercellular transport, and cell signaling

The Lived Experience Of Inpatients On Contact Precautions

This phenomenological study explores the lived experience of patients on contact precautions. While current literature reports mixed compliance rates among healthcare-workers, increased workload for staff, less time spent at the bedside, higher rates of adverse events, and higher rates of anxiety and depression for patients on contact precautions, few studies describe the patient\u27s perception. Interviews were conducted identifying the following themes: patient understanding of contact precautions, cleanliness and dirtiness, family/visitor perceptions, patient priorities, delays in care and staff attitudes, and protecting not isolating. Contact precautions are not perceived as burdensome, isolating, or distressing by most patients. Families and patients showing signs of distress should be supported with information about transmission risks, infectious status, and the use of contact precautions routinely and frequently during a hospital stay. Staff compliance with contact precautions is regularly observed and analyzed by patients as reflective of hospital cleanliness

LMDA New & Noteworthy, May 2019

Contents include: Crossing Borders, Pt. 2: Action in a Time of Division; Q&A | Katie Welsh; Post-Apprenticeship Reflections: How We Learned by Doing; The Kennedy Center New Play Dramaturgy Intensive 2019; Call for Translators.https://soundideas.pugetsound.edu/lmdanewsletter/1041/thumbnail.jp

Media Literacy in Teacher Education: A Good Fit across the Curriculum

Abstract Current preoccupations in teacher education reform include data gathering, teaching technique, and preparing PK-12 students for standardized tests. The purpose of American education has been reduced to economic benefit. Concerns with ethical behavior, the good life, and democratic citizenship have fallen by the wayside except perhaps in a single social foundations course. Media literacy education infused in the teacher education curriculum offers one way to restore purpose to teacher education, encouraging both pre-service teachers and their students to think critically about their media-dominated society

Ultraluminous infrared galaxies: mergers of sub-L* galaxies?

A sample of 27 low-redshift, mostly cool, ultraluminous infrared galaxies (ULIRGs) has been imaged at 1.6 μm with the Hubble Space Telescope (HST) Near-Infrared Camera and Multi-Object Spectrometer (NICMOS). The majority (67%) of the sample's galaxies are multiple-nucleus galaxies with projected separations of up to 17 kpc, and the rest of the sample (33%) are single-nucleus galaxies, as determined by the NICMOS angular resolution limit. The average observed, integrated (host+nucleus) H magnitude of our HST H sample ULIRGs is -24.3, slightly above that of an L* galaxy (MH = -24.2), and 52% of the sample's galaxies have sub-L* luminosities. The ULIRGs in the HST H sample are not generated as a result of the merging of two luminous (i.e., ≥L*) spiral galaxies. Instead, the interactions and mergers occur in general between two, or in some cases more, less massive sub-L* (0.3-0.5L*) galaxies. Only one out of the 49 nuclei identified in the entire HST H sample has the properties of a bright quasar-like nucleus. On average, the brightest nuclei in the HST H sample galaxies (i.e., cool ULIRGs) are 1.2 mag fainter than warm ULIRGs and low-luminosity Bright Quasar Survey quasars (BQS QSOs) and 2.6 mag fainter than high-luminosity BQS QSOs. Since the progenitor galaxies involved in the merger are sub-L* galaxies, the mass of the central black hole in these ULIRGs would be only about (1-2) × 107 M☉, if the bulge-to-black hole mass ratio of nearby galaxies holds for ULIRGs. The estimated mass of the central black hole is similar to that of nearby Seyfert 2 galaxies but at least 1 order of magnitude lower than the massive black holes thought to be located at the center of high-luminosity QSOs. Massive nuclear starbursts with constant star formation rates of 10-40 M☉ yr-1 could contribute significantly to the nuclear H-band flux and are consistent with the observed nuclear H-band magnitudes of the ULIRGs in the HST H sample. An evolutionary merging scenario is proposed for the generation of the different types of ULIRGs and QSOs on the basis of the masses of the progenitors involved in the merging process. According to this scenario, cool ULIRGs would be the end product of the merging of two or more low-mass (0.3L*-0.5L*) disk galaxies. Warm ULIRGs and low-luminosity QSOs would be generated by a merger involving intermediate-mass (0.5 L*) disk galaxies. Under this scenario, warm ULIRGs could still be the dust-enshrouded phases of UV-bright low-luminosity QSOs, but cool ULIRGs, which are most ULIRGs, would not evolve into QSOs

Evidence for variable selective pressures at MC1R

It is widely assumed that genes that influence variation in skin and hair pigmentation are under selection. To date,the melanocortin 1 receptor (MC1R) is the only gene identified that explains substantial phenotypic variance inhuman pigmentation. Here we investigate MC1R polymorphism in several populations, for evidence of selection.We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations underrelaxation of strong functional constraint outside Africa

Estimating Costs and Benefits Associated with Evidence-Based Violence Prevention: Four case studies based on the Fourth R program

Teen violence in dating and peer relationships has huge costs to society in numerous areas including health care, social services, the workforce and the justice system. Physical, psychological, and sexual abuse have long-lasting ramifications for the perpetrators as well as the victims, and for the families involved on both sides of that equation. An effective violence prevention program that is part of a school’s curriculum is beneficial not only for teaching teenagers what is appropriate behaviour in a relationship, but also for helping them break the cycle of violence which may have begun at home with their own maltreatment as children. The Fourth R program is an efficacious violence prevention program that was developed in Ontario and has been implemented in schools throughout Canada and the U.S. Covering relationship dynamics common to dating violence as well as substance abuse, peer violence and unsafe sex, the program can be adapted to different cultures and to same-sex relationships. The program, which gets its name from the traditional 3Rs — reading, ’riting and ’rithmetic — offers schools the opportunity to provide effective programming for teens to reduce the likelihood of them using relationship for violence as they move into adulthood. The federal government has estimated that the societal costs of relationship violence amount to more than $7 billion. These costs can continue to be incurred through the legal and health-care systems as the ripple effects of violence play out over the years, even after a relationship has ended. Other types of violence are also costly to society and not just in terms of dollars, but in young lives diverted into criminal activity. Up to 15 per cent of youth who become involved with the justice system grow into serious adult offenders who develop lengthy criminal careers. Yet, research shows that if prevention programs such as the Fourth R can deter just one 14-year-old high-risk juvenile from a life of crime, up to$5 million can be saved in costs to society

Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles

BACKGROUND: The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization. METHODS: Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization. RESULTS: Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinization, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone. CONCLUSIONS: The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize