Life Sciences Commons^™

Tsc2 Modulates Actin Cytoskeleton And Focal Adhesion Through Tsc1-Binding Domain And The Rac1 Gtpase, Elena Goncharova, Dmitry Goncharov, Daniel J. Noonan, Vera P Krymskaya

Molecular and Cellular Biochemistry Faculty Publications

Tuberous sclerosis complex (TSC) 1 and TSC2 are thought to be involved in protein translational regulation and cell growth, and loss of their function is a cause of TSC and lymphangioleiomyomatosis (LAM). However, TSC1 also activates Rho and regulates cell adhesion. We found that TSC2 modulates actin dynamics and cell adhesion and the TSC1-binding domain (TSC2-HBD) is essential for this function of TSC2. Expression of TSC2 or TSC2-HBD in TSC2-/- cells promoted Rac1 activation, inhibition of Rho, stress fiber disassembly, and focal adhesion remodeling. The down-regulation of TSC1 with TSC1 siRNA in TSC2-/- cells activated Rac1 and induced loss of …

A Subset Of Liver Nk T Cells Is Activated During Leishmania Donovani Infection By Cd1d-Bound Lipophosphoglycan, Joseph L. Amprey, Jin S. Im, Salvatore J. Turco, Henry W. Murray, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli, Gerald F. Späth

Molecular and Cellular Biochemistry Faculty Publications

Natural killer (NK) T cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. In the current work, we show increased susceptibility of NK T cell–deficient CD1d^−/− mice to Leishmania donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells in wild-type animals. The elicited response was Th1 polarized, occurred as early as 2 h after infection, and was independent from …

Natural Selection Drives Altitudinal Divergence At The Albumin Locus In Deer Mice, Peromyscus Maniculatus, Jay F. Storz, Jean M. Dubach

Jay F. Storz Publications

In populations that are distributed across steep environmental gradients, the potential for local adaptation is largely determined by the spatial scale of fitness variation relative to dispersal distance. Since altitudinal gradients are generally characterized by dramatic ecological transitions over relatively short linear distances, adaptive divergence across such gradients will typically require especially strong selection to counterbalance the homogenizing effect of gene flow. Here we report the results of a study that was designed to test for evidence of adaptive divergence across an altitudinal gradient in a natural population of deer mice, Peromyscus maniculatus. We conducted a multilocus survey of …

Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle

Dartmouth Scholarship

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by inter- leukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this 􏰀-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in …

Performance Of Mouse Lines Divergently Selected For Heat Loss When Exposed To Different Environmental Temperatures. I. Reproductive Performance, Pup Survival, And Metabolic Hormones, P. M. Kgwatalala, J. L. Deroin, Merlyn K. Nielsen

Department of Animal Science: Faculty Publications

Mouse populations differing in metabolic rate have been developed through selection for high (MH) and low (ML) heat loss, along with the unselected controls (MC). Objectives of the study were to compare the MH, ML, and MC lines for reproductive performance, pup survival, and metabolic hormones when reared at 12, 22, and 31°C, and to search for line × environment interactions. Conception and litter size were recorded on the parent generation mice introduced to the environments at 11 wk of age and bred after a 3-wk acclimatization period. Survival of pups (pre-weaning to 3 wk; post-weaning from 3 to 9 …

Topical Cidofovir Is More Effective Than Is Parenteral Therapy For Treatment Of Progressive Vaccinia In Immunocompromised Mice, Donald F. Smee, K. W. Bailey, M-H. Wong, M. K. Wandersee, R. W. Sidwell

Animal, Dairy, and Veterinary Science Faculty Publications

Background.Severe complications may arise as a result of virus dissemination after smallpox (live vaccinia virus) vaccination, particularly in immunocompromised individuals. We developed a new mouse model for studying the effects of antiviral agents on progressive vaccinia virus infections.

Methods.Hairless mice were treated with cyclophosphamide (100 mg/kg/day) every 4 days starting 1 day before vaccinia virus exposure to wounded skin. Primary lesions progressed in severity, satellite lesions developed, and the infection eventually killed the mice.

Results.Topical treatment with 1%‐cidofovir cream (twice daily for 7 days) was much more effective in reducing the severity of primary lesions and the number of satellite …

Performance Of Mouse Lines Divergently Selected For Heat Loss When Exposed To Different Environmental Temperatures. Ii. Feed Intake, Growth, Fatness, And Body Organs, P. M. Kgwatalala, Merlyn K. Nielsen

Department of Animal Science: Faculty Publications

Mouse populations differing in metabolic rate have been developed through selection for high (MH) and low (ML) heat loss, along with the unselected controls (MC). Objectives of the study were to compare the MH, ML, and MC lines for feed intake, growth, body fatness, and organ weights when reared at 12, 22, and 31°C, and investigate potential line × environment interactions. Feed intake was recorded weekly from 3 to 9 wk of age, and BW at 3, 6, and 9 wk of age. Body fat percent and organ weights were measured at 9 wk of age. No line × environment …