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NAD+dependent deacetylase, SIRT3 is a bona fide mitochondrial metabolic stress sensor. It has been linked to the regulation of the mitochondrial acetylome and activation of several metabolic enzymes (e.g., MnSOD) to protect mitochondrial function and redox homeostasis, which are vital for survival, excitability and synaptic signaling of neurons mediating short and long term memory formation as well as retention. The goal of the current study was to determine the consequences of SIRT3 deletion on hippocampal-dependent behavioral tests (Y-maze, Crawley’s Sociability and Morris Water Maze) in 18-months old male and female Sirt3+/+and Sirt3-/-mice. Our results demonstrated that both Sirt3+/+and Sirt3-/- male mice displayed significant exploration bias for the novel arm compared to the start and familiar arms in Y-maze test, while Sirt3+/+and Sirt3-/-females failed to distinguish between the novel and start arms, suggesting female mice are more prone to hippocampal dependent short term memory loss independent of SIRT3 function. Crawley’s Sociability tests also showed both Sirt3+/+and Sirt3-/-female mice demonstrated impaired sociability. However, only Sirt3-/-females presented impaired social novelty. There were no sociability or social novelty impairments in male mice from both genetic backgrounds. Finally, hippocampal-dependent spatial learning and long-term memory were assessed via the Morris Water Maze. Both female and male Sirt3-/- mice demonstrated impaired spatial memory retention implying that SIRT3 plays a role in long term memory function.We are currently examining changes in glutamate receptor subunits and pre/post-synaptic marker gene expression as well as Sholl analysis to determine changes to the dendritic arborization. We will also present the mitochondrial function data as well as activity of mitochondrial enzymes which have shown to be SIRT3 deacetylation targets to establish a link between SIRT3 mediated mitochondrial redox homeostasis and cognition.

Individuals who choose not to couple live a unique experience. This study examines the evolution of the social pressures and expectations, directed toward men, in regards to choosing a partner and forming a lifelong union. The study gathered the attitudes, opinions, and experiences of adult Canadian males regarding this topic. The participants include men who have avoided lifelong unions, such as marriage and cohabitation, in the 1960s, and men who have avoided lifelong unions from 2005 to the present. The data for this study was created through conducting semi-structured interviews. I interviewed ten men who rejected lifelong unions in the 1960s, and ten men who have done so since 2005. I focused on the male experience because the majority of the existing sociological research pertaining to lifelong unions is centered on the couple, and focuses on the shared experience of marriage. I am interested in questioning marriage as a norm, and the research suggests socially accepted alternatives to coupling and lifelong unions. The study provides insight on how the experiences of single men have changed over the past fifty years. The results from the study suggest that marriage is still the norm, and that it is still difficult to question this norm. When the participants did not conform to the norm, they expressed being subject to stereotyping or discrimination. The study also suggests that the participants who are currently single experience less pressure to form a lifelong union than the participants who were single in the 1960s. However, the pressure to couple remains strong, and the participants who are currently single experience intense age-related pressure that increases the longer they remain single.

M2 is a homotetrameric membrane protein critical to generation of membrane curvature in the budding stage of the influenza A virus life cycle. We have designed and interpreted site-directed spin-label electron paramagnetic resonance spectroscopy (SDSL-EPR) experiments on the conformation and dynamics of M2 in lipid bilayers of different propensities for membrane curvature generation. We have obtained data for full length M2 protein spin labelled at multiple sites in the C-terminal juxtamembrane region, which forms a membrane associated amphipathic helix. Continuous wave (CW) and pulsed EPR spectra provide evidence that M2 adopts two conformational states in bilayers, and that the propensity of lipids to form membranes of differing curvature dictates the relative population of these states. Multicomponent simulation of CW-EPR spectra further show lipid bilayers of the highly curved cubic phases stabilize an immobilized conformation of M2, hypothesized to be relevant for curvature generation. We have also characterized the size distribution of large unilamellar vesicles of lipids of different curvature generation propensities alone and in the presence of full-length M2 using dynamic light scattering (DLS).

We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution, and increased renal medullary phosphodiesterase 5A (PDE5A) protein. The present study examined the role of the renin-angiotensin-aldosterone system (RAAS) in this mechanism. Virgin females were treated for 14 days with NIF (10 mg·kg−1·day−1via diet), NIF with spironolactone [SPR; mineralocorticoid receptor (MR) blocker, 200–300 mg·kg−1·day−1via diet], NIF with losartan [LOS; angiotensin type 1 (AT1) receptor blocker, 20 mg·kg−1·day−1via diet], enalapril (ENAL; angiotensin-converting enzyme inhibitor, 62.5 mg/l via water), or vehicle (CON). Mean arterial pressure (MAP) was reduced 7.4 ± 0.5% with NIF, 6.33 ± 0.5% with NIF + SPR, 13.3 ± 0.9% with NIF + LOS, and 12.0 ± 0.4% with ENAL vs. baseline MAP. Compared with CON (3.6 ± 0.3%), plasma volume factored for body weight was increased by NIF (5.2 ± 0.4%) treatment but not by NIF + SPR (4.3 ± 0.3%), NIF + LOS (3.6 ± 0.1%), or ENAL (4.0 ± 0.3%). NIF increased PDE5A protein abundance in the renal inner medulla, and SPR did not prevent this increase (188 ± 16 and 204 ± 22% of CON, respectively). NIF increased the α-subunit of the epithelial sodium channel (α-ENaC) protein in renal outer (365 ± 44%) and inner (526 ± 83%) medulla, and SPR prevented these changes. There was no change in either PDE5A or α-ENaC abundance vs. CON in rats treated with NIF + LOS or ENAL. These data indicate that the PVE and renal medullary adaptations in response to chronic vasodilation result from RAAS signaling, with increases in PDE5A mediated through AT1receptor and α-ENaC through the MR.