Well-being and Engineering: Personal and Professional Well-Being Experiences of Tenured Female Engineering Faculty

This poster presents early results from a doctoral research study. Designed to capture and share the stories of faculty, this qualitative research study examined the lived experience of female engineering faculty from several universities and engineering sub-disciplines to uncover how these women incorporate well-being across their personal and professional lives in support of their professional success as they navigate the faculty pathway. This poster will present the well-being experiences and findings for one study participant, Frances, an African American engineering faculty member who has navigated the faculty pathway through tenure and into an administrative position. Readers are encouraged to reflect critically on their own well-being experiences as well as the importance of well-being within engineering and higher education institution

Women Engineering Faculty Well-Being: An Interpretative Phenomenological Analysis

This study examined the lived experiences of women as they navigate faculty pathways in engineering. This qualitative research study centered on the well-being journeys of seven women who have achieved tenure as engineering faculty to uncover how these women psychologically experienced and incorporated well-being across their personal and professional lives in support of their success, happiness, and satisfaction. Leveraging qualitative research techniques aligned with the interpretative phenomenological analysis (IPA) methodology, this study elicited and systematically analyzed accounts of well-being across participants’ professional and personal life spaces. The well-being journeys of seven participants, JoAnn, Rose, Marie, Allison, Dylan, Mary, and Gabriella, who have navigated the faculty pathway to tenure and beyond in several universities and engineering sub-disciplines are described here. Their rich stories weave together successes and challenges commonly faced by many in engineering including managing demands of professional and personal roles, establishing trusting relationships, resilience against marginalizing cultures and climates, and supporting one’s own success within engineering departments and universities widely. This work reveals four psychological patterns, or themes, from the accounts of women engineering educators in order to illuminate challenges faced by women faculty within engineering disciplines as well as to offer examples of what actionable well-being strategies could look like for faculty and for those who support them. Through the analysis and interpretation of their accounts, readers gain insight into challenges faced, strategies engaged, and benefits of maintaining well-being as a woman faculty member. Their experiences illustrate the subtle and overt ways faculty identities and success may be marginalized by immediate colleagues and how a faculty member may ensure her own success and well-being through seeking positive relationships in external spaces. By presenting participants’ accounts, the findings demonstrate approaches faculty could potentially adopt to circumvent toxic professional environments and enhance their own well-being. This study provides strategies that can be adopted by others in their own pursuit of professional success (however success may be defined by the individual)

A Novel p.Leu(381)Phe Mutation in Presenilin 1 is Associated with Very Early Onset and Unusually Fast Progressing Dementia as well as Lysosomal Inclusions Typically Seen in Kufs Disease

Whole exome sequencing in a family with suspected dominant Kufs disease identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who, along with their father, developed progressive dementia and motor deficits in their early 30s. All affected relatives had unusually rapid disease progression (on average 3.6 years from disease onset to death). In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease. However his brain autopsy demonstrated typical changes of Alzheimer disease

ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons

Miles-Carpenter syndrome (MCS) was described in 1991 as an XLID syndrome with fingertip arches and contractures and mapped to proximal Xq. Patients had microcephaly, short stature, mild spasticity, thoracic scoliosis, hyperextendable MCP joints, rocker-bottom feet, hyperextended elbows and knees. A mutation, p.L66H, in ZC4H2, was identified in a XLID resequencing project. Additional screening of linked families and next generation sequencing of XLID families identified three ZC4H2 mutations: p.R18K, p.R213W and p.V75in15aa. The families shared some relevant clinical features. In silico modeling of the mutant proteins indicated all alterations would destabilize the protein. Knockout mutations in zc4h2 were created in zebrafish and homozygous mutant larvae exhibited abnormal swimming, increased twitching, defective eye movement and pectoral fin contractures. Because several of the behavioral defects were consistent with hyperactivity, we examined the underlying neuronal defects and found that sensory neurons and motoneurons appeared normal. However, we observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specificmarkers showed a specific loss of V2 interneurons in the brain and spinal cord, likely arising from mis-specification of neural progenitors. Injected human wt ZC4H2 rescued the mutant phenotype. Mutant zebrafish injectedwith human p.L66H or p.R213W mRNA failed to be rescued, while the p.R18K mRNA was able to rescue the interneuron defect. Our findings clearly support ZC4H2 as a novel XLID gene with a required function in interneuron development. Loss of function of ZC4H2 thus likely results in altered connectivity ofmany brain and spinal circuits

The Role of Protonation States in Ligand-Receptor Recognition and Binding

In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa’s and that protonation states frequently change from unbound to bound states. These protonation changes result in proton uptake/release, which in turn causes the pHdependence of the binding. Indeed, experimental data strongly suggest that almost any binding is pH-dependent and to be correctly modeled, the protonation states must be properly assigned prior to and after the binding. One may accurately predict the protonation states when provided with the structures of the unbound proteins and their complex; however, the modeling becomes much more complicated if the bound state has to be predicted in a docking protocol or if the structures of either bound or unbound receptor-ligand are not available. The major challenges that arise in these situations are the coupling between binding and protonation states, and the conformational changes induced by the binding and ionization states of titratable groups. In addition, any assessment of the protonation state, either before or after binding, must refer to the pH of binding, which is frequently unknown. Thus, even if the pKa’s of ionizable groups can be correctly assigned for both unbound and bound state, without knowing the experimental pH one cannot assign the corresponding protonation states, and consequently one cannot calculate the resulting proton uptake/release. It is pointed out, that while experimental pH may not be the physiological pH and binding may involve proton uptake/release, there is a tendency that the native receptor-ligand complexes have evolved toward specific either subcellular or tissue characteristic pH at which the proton uptake/release is either minimal or absent. - See more at: http://www.eurekaselect.com/110454/article#sthash.pkwzcCNr.dpu

Molecular Mechanisms of Disease-Causing Missense Mutations

Genetic variations resulting in a change of amino acid sequence can have a dramatic effect on stability, hydrogen bond network, conformational dynamics, activity and many other physiologically important properties of proteins. The substitutions of only one residue in a protein sequence, so-called missense mutations, can be related to many pathological conditions, and may influence susceptibility to disease and drug treatment. The plausible effects of missense mutations range from affecting the macromolecular stability to perturbing macromolecular interactions and cellular localization. Here we review the individual cases and genome-wide studies which illustrate the association between missense mutations and diseases. In addition we emphasize that the molecular mechanisms of effects of mutations should be revealed in order to understand the disease origin. Finally we report the current state-of-the-art methodologies which predict the effects of mutations on protein stability, the hydrogen bond network, pH-dependence, conformational dynamics and protein function

The pKa shift of two ionizable residues βGlu26 and βGlu69 on (A) HLA-DP2 binds to peptides (Four types as “natural”, “strong”, “weak” and “DR”, the same to the followings) (B) peptides bind to the complex (Be+protein) (C) (Be+peptides) complex binds to HLA-DP2 protein from pKa of native unbond protein.

<p>The pKa value was calculated as the average of 10 structures for each type of peptides.</p