Relationship Between Structure and Function in Nickel Proteins and Enzymes

Nickel is a rarely used but biologically important metal that is utilized in all three domains of life. In nickel utilizing organisms there is a corresponding trafficking system specifically designed to capture nickel, deliver, and export excess nickel to prevent toxic effects. It is critical to understand the mechanisms by which organisms achieve metal selectivity to duplicate or disrupt this process for the benefit of human health and to further understanding of regulation mechanisms in biology. RcnR is a Ni(II) and Co(II) responsive transcriptional regulator in E. coli. The research reported in this dissertation focuses on the relationship between structure and function in two hypothesized metal ligand residues, Glu34 and Glu63. The results of these studies indicate that Glu34 is a Co(II) ligand and Glu63 is both a Ni(II) and Co(II) ligand. It is clear from the results of these studies that there is little correlation between metal structure and function in RcnR, and that studies of metal site structure or function alone cannot be used to determine metal response or residue importance. It is clear from analysis of this family of transcriptional regulators that although homologous, they have divergent mechanisms. Reactive oxygen species (ROS) are a natural byproduct of aerobic metabolism and inflammation, and can be generated through environmental factors such as radiation damage, pollution, and smoking. ROS such as superoxide can cause damage to DNA, lipids, and proteins if left unchecked. Superoxide dismutases are a family of enzymes that catalyze the disproportionation of superoxide to prevent its harmful effects. One of the goals of this dissertation is to investigate how NiSOD exerts control over the redox state of the nickel centers. NiSOD is a hexamer that cannot be fully oxidized and thus remains 50% Ni(II)/50% Ni(III). One possible reason this occurs is by crosstalk of the nickel centers through a hydrogen bonding network involving His53. Disruption of this crosstalk was attempted by mutation of His53 to alanine. While the experimental evidence indicates the mutation did not disrupt the crosstalk, it is apparent that the entire ~ 40 Å hydrogen bonding network is important for modulating the catalytic mechanism

Saint Sebastian Attended by Irene: An Iconographic Study

The artists of the Baroque, rejecting the traditional conception of Sebastian, portray the formerly invincible saint as wounded, suffering, no longer victoriously partaking of the fruits of his glorious martyrdom, but being found and cared for by Irene, the widow of the Christian martyr Castulus. Such a change in iconography involves both a shift of the outward and visible as well as the intrinsic content of the pictorial matter. the significance of this thematic revolution has often been overlooked because it parallels the stylistic developments of the age, which, until recently, have captured more fully the imagination of art historians. Therefore, it is the purpose of this paper to deal specifically with this iconographic change which involves the portrayal of the moment when the saint is found and cared for by Irene

Saint Sebastian Attended by Irene: An Iconographic Study

The artists of the Baroque, rejecting the traditional conception of Sebastian, portray the formerly invincible saint as wounded, suffering, no longer victoriously partaking of the fruits of his glorious martyrdom, but being found and cared for by Irene, the widow of the Christian martyr Castulus. Such a change in iconography involves both a shift of the outward and visible as well as the intrinsic content of the pictorial matter. the significance of this thematic revolution has often been overlooked because it parallels the stylistic developments of the age, which, until recently, have captured more fully the imagination of art historians. Therefore, it is the purpose of this paper to deal specifically with this iconographic change which involves the portrayal of the moment when the saint is found and cared for by Irene

How Female Principals Communicate: Verbal and Nonverbal Micropolitical Communication Behaviors of Female Anglo and Hispanic School Principals

None [of these principals] had adopted male behaviors entirely, but all had relaxed the stereotypic restrained and closed female behaviors and speech reported in research of two decades ago

'You must remember you are New Zealanders': identity-making in First World War New Zealand troopship magazines

This thesis presents a sustained analysis of New Zealand World War I troopship magazines, as a distinct sub-genre of soldierly print culture. The New Zealand Expeditionary Force had the longest journey to and from the war, and the thesis argues that the 120 magazines produced en route are a significant, if neglected source, given their frequent publication over the whole war, their popularity and the breadth of the contributors. This thesis builds on, and contributes to, international scholarship on soldierly magazines from the First World War, and to the New Zealand historiography of the War. The thesis identifies questions of identity as a central concern of these magazines. Underpinning the analysis is an understanding of identity as a dynamic process, negotiated by imagined and interpretive communities, through narrative. While not everyone contributed to the magazines everyone was included in the imagined readership. The magazines contain representations and discussions from the bottom up. They reveal how New Zealand soldiers of all ranks were imagining the war, and their role in it. They also show how travelling back, these men envisaged their return home, and the way their memories of the war and their sense of themselves as New Zealanders might shape the future. Individual chapters investigate how this community used their magazines to reflect on the imperial-national relationship (revealing dual loyalties without conflict of interest) and on their reasons for enlisting including a strong sense of duty, conceived in plurivalent ways (straddling personal, national and imperial loyalties); their interpretation of the Gallipoli Campaign and the Anzac legend which many saw as defining them as New Zealand soldiers and which became the measure for later troops; the articulation of multiple identities including regional, military and national (with the latter dominating); the influence of landscapes both overseas and back home on writers’ notions of identity and personal well-being. The visibility of Māori is a distinctive feature of these conversations. A separate chapter investigates what happened to these ideas in the homeward magazines, and shows that men were not disillusioned but optimistic about leaving the war behind and shaping New Zealand’s future

The portrayal of teenage sexuality in young adult literature

The focus of this study was an investigation in to how teenage sexuality is portrayed in young adult literature. The purpose of this research was to investigate the portrayal of teenage sexuality within young adult literature in the United States. The methodology of this study was a quantitative content analysis of literature intended for young adult readers. Twenty young-adult books with teenage sexuality as a theme and a publication date within the last ten years were randomly selected from the following lists: 2009 Young Adult Library Services Association (Y ALSA): Quick Picks for Reluctant Readers, Best Books for Young Adults, including the 2008 thematic list entitled Sex is... This content analysis includes the type of sexual activity of prominent characters, risk factors or influences in the characters\u27 lives, and ramifications following sexual activity. The majority teenager characters level of sexuality was sex, I 00% of teenagers had one or more influential factors for sexuality in their lives, and emotional ramifications were the most common consequence of sexual activity, abstinence to sex

Strengthening Community Involvement in Grant Review: Insights from the Community–University Research Partnership (CURES) Pilot Review Process

In 2007, the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan received a Clinical and Translational Science Award (CTSA). Within MICHR, the Community Engagement (CE) program supports partnership efforts between researchers, practitioners, and community‐based organizations in specific focal communities throughout Michigan. A key component of the CE program is the Community Engagement Coordinating Council, a group that provides input and guidance on program priorities, strategic planning, and reviews pilot funding proposals for community–academic partnerships. This paper will describe a unique MICHR pilot funding mechanism for Community–University Research Partnerships (CURES) with an emphasis on the ways that community partners are involved in the review process, as well as the benefits, challenges, and insights gained over 5 years of pilot review. There is a growing need for community involvement and expertise in review of funding proposals for community‐engaged research at both institutional and federal levels. The CURES pilot review process is one example of an institutional effort to engage community partners in university funding decisions and has demonstrated clear benefit toward accomplishing the aims of the CTSA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106809/1/cts12141.pd

In vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophy

Aims The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice. Methods and Results Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy. Conclusions MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases