Nerve growth factor inhibits sympathetic neurons’ response to an injury cytokine

Axonal damage to adult peripheral neurons causes changes in neuronal gene expression. For example, axotomized sympathetic, sensory, and motor neurons begin to express galanin mRNA and protein, and recent evidence suggests that galanin plays a role in peripheral nerve regeneration. Previous studies in sympathetic and sensory neurons have established that galanin expression is triggered by two consequences of nerve transection: the induction of leukemia inhibitory factor (LIF) and the reduction in the availability of the target-derived factor, nerve growth factor. It is shown in the present study that no stimulation of galanin expression occurs following direct application of LIF to intact neurons in the superior cervical sympathetic ganglion. Injection of animals with an antiserum to nerve growth factor concomitant with the application of LIF, on the other hand, does stimulate galanin expression. The data suggest that the response of neurons to an injury factor, LIF, is affected by whether the neurons still receive trophic signals from their targets.

Cell Cycle–regulated Transcription in Fission Yeast: Cdc10–Res Protein Interactions during the Cell Cycle and Domains Required for Regulated Transcription

In Schizosaccharomyces pombe the MBF (DSC1) complex mediates transcriptional activation at Start and is composed of a common subunit called Cdc10 in combination with two alternative DNA-binding partners, Res1 and Res2. It has been suggested that a high-activity MBF complex (at G1/S) is switched to a low-activity complex (in G2) by the incorporation of the negative regulatory subunit Res2. We have analyzed MBF protein–protein interactions and find that both Res proteins are associated with Cdc10 throughout the cell cycle, arguing against this model. Furthermore we demonstrate that Res2 is capable of interacting with a mutant form of Cdc10 that has high transcriptional activity. It has been shown previously that both Res proteins are required for periodic cell cycle–regulated transcription. Therefore a series of Res1–Res2 hybrid molecules was used to determine the domains that are specifically required to regulate periodic transcription. In Res2 the nature of the C-terminal region is critical, and in both Res1 and Res2, a domain overlapping the N-terminal ankyrin repeat and a recently identified activation domain is important for mediating cell cycle–regulated transcription.

A human model for multigenic inheritance: Phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus

Reduced penetrance in genetic disorders may be either dependent or independent of the genetic background of gene carriers. Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with ≈50% of familial cases being heterozygous for mutations in the receptor tyrosine kinase RET. Even when identified, the penetrance of RET mutations is only 50–70%, gender-dependent, and varies with the extent of aganglionosis. We searched for additional susceptibility genes which, in conjunction with RET, lead to phenotypic expression by studying 12 multiplex HSCR families. Haplotype analysis and extensive mutation screening demonstrated three types of families: six families harboring severe RET mutations (group I); and the six remaining families, five of which are RET-linked families with no sequence alterations and one RET-unlinked family (group II). Although the presence of RET mutations in group I families is sufficient to explain HSCR inheritance, a genome scan reveals a new susceptibility locus on 9q31 exclusively in group II families. As such, the gene at 9q31 is a modifier of HSCR penetrance. These observations imply that identification of new susceptibility factors in a complex disease may depend on classification of families by mutational type at known susceptibility genes.

Inhibition of MHC class I-restricted antigen presentation by γ2-herpesviruses

The γ-herpesviruses, in contrast to the α- and β-herpesviruses, are not known to inhibit antigen presentation to CD8+ cytotoxic T lymphocytes (CTLs) during lytic cycle replication. However, murine γ-herpesvirus 68 causes a chronic lytic infection in CD4+ T cell-deficient mice despite the persistence of a substantial CTL response, suggesting that CTL evasion occurs. Here we show that, distinct from host protein synthesis shutoff, γ-herpesvirus 68 down-regulates surface MHC class I expression on lytically infected fibroblasts and inhibits their recognition by antigen-specific CTLs. The viral K3 gene, encoding a zinc-finger-containing protein, dramatically reduced the half-life of nascent class I molecules and the level of surface MHC class I expression and was by itself sufficient to block antigen presentation. The homologous K3 and K5 genes of the related Kaposi's sarcoma-associated virus also inhibited antigen presentation and decreased cell surface expression of HLA class I antigens. Thus it appears that an immune evasion strategy shared by at least two γ-herpesviruses allows continued lytic infection in the face of strong CTL immunity.

The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity

The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such as pregnenolone 16α-carbonitrile (PCN), which induce cytochrome P450 3A (CYP3A) expression and protect the body from harmful chemicals. In this study, we demonstrate that PXR is activated by the toxic bile acid lithocholic acid (LCA) and its 3-keto metabolite. Furthermore, we show that PXR regulates the expression of genes involved in the biosynthesis, transport, and metabolism of bile acids including cholesterol 7α-hydroxylase (Cyp7a1) and the Na+-independent organic anion transporter 2 (Oatp2). Finally, we demonstrate that activation of PXR protects against severe liver damage induced by LCA. Based on these data, we propose that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid. These findings suggest that PXR agonists may prove useful in the treatment of human cholestatic liver disease.

U-M Softball Team, 1992

Front Row: Karla Kunnen, Shelley Bawol, co-captain Stacey Heam, Patti Benedict, Kari Kunnen.

Middle Row: Michelle Silver, Lesa Arvia, Sue Sieler, Mary Campana,co-captain Heather Lyke.

Back Row: head coach Carol Hutchins, assistant coach Cathy Wylie, Kim Clark, Kelly Kovach, Kelly Forbis, Julie Clarkson, Tina Martin. Trainer Sue Weitzman, assistant coach Carol Bruggeman

Not Pictured: Kerry Sayers, Manager Debbie Kleban

U-M Softball Team, 1997

Front Row: Sara Griffin, Kellyn Tate, Jessica Lang (captain), Kelly Holmes, Jen Smith, Tracy Taylor, Jen McKittrick, Lisa Kelley.

Back Row: Cathy Davie, Traci Conrad, Stacey Judd, Jamie Gillies, Melissa Gentile, Karmen Lappo, Pam Kosanke, Tammy Mika, Lisa Beard.

Not Pictured: Mary Adams.

U-M Softball Team, 1998

Back Row: Melissa Taylor, Christine Garza, Courtney Murdock, Melissa Gentile, Rebecca Tune, Marie Barda, Kim Bugel

Middle Row: Stacey Judd, Karmen Lappo, Traci Conrad, Tammy Mika, Cathy Davie, Pam Kosanke, Jamie Gillies

Front Row: Sara Griffin, Jennifer McKittrick (captain), Lisa Kelley, Kellyn Tate (captain) Blanc LeBron (manager)

1989 University of Michigan Baseball Team

Top Row: student mngr. John Rutherford, student trainer Steve Fitch, Dave Everly, Dave Julier, Brian Korson, Jason Pfaff, Andy Fairman, Tracy Piehl, Todd Marion, Matt Morse, Steve Buerkel, trainer Kim Hart, student mngr. Mike Gaynor

Middle Row: asst. coach John Young, asst. coach Ted Mahan, Todd Winston, Dan Ruff, Greg Haeger, Kirt Ojala, Rick Leonard, Russell Brock, Jeff Tanderys, Eric Persinger, Mike Matheny, Tim Flanelly, asst. coach Chuck Froning, coach Bud Middaugh

Front Row: John Locker, Greg McMurtry, Tim Lata, Mike Grimes, Doug Kaiser, Dave Peralta, Jim Durham, Kourtney Thompson, mngr. Ed Turek, Phil Price, Ross Powell, Stacey Katlin, Chris Gagin

1990 University of Michigan Baseball Team

Top Row: groundskeeper Erich Keil, Chris Michalek, Scott Winterlee, Matt Copp, Bryan Santo, Ron Buff, Toby Brzoznowski, Eric Persinger, Derek Matthison, Joe Mooney, Pat Maloney, Scott Schorer, Scott Timmerman, student trainer Earl Wenk, student manager Kevin Lewis

Middle Row: trainer Kim Hart, grad. Asst. Ed Turek, asst. coach Ted Mahan, Todd Konuszewski, Mike Matheny, Dave Julier, Steve Buerkel, asst. coach Ace Adams, coach Moby Benedict

Front Row: Russell Brock, Jeff Tanderys, Da ruff, Brian Korson, Stacey Katlin, co-captain Phil Price, coach Bill Freehan, co-captain Kirt Ojala, Rick Leonard, Greg Haeger, Dave Everly, Matt Morse, Jason Pfaff

1993 Men's Gymnastics Team

Back Row: Mat Burleson, Evan Feldman, Bob Young, Chris Onuska, Brad Terris, Geoff Bidwell, Kris Klinger, Jason Taft

Middle Row: head coach Bob Darden, Chris Burkhardt, Rich Dopp, Chris Bonifiorti, Raul Molina, John Besancon, Coney Huttenga, Paul Mariani, Brian Winkler, mngr. Stacey Shingte, asst. coach Mike Milidonis

Front Row: Royce Toni, Ben Verrall, Seth Rubin, Josh Miners, Matt Marsich, Jorge Camacho, Mike Mott, trainer Jon Fetter

1994 Men's Gymnastics Team

Fourth Row (left to right): Jerrod Farrand, Lawrence Neukom, Flavio Martins, Brad Terris, Jason MacDonald, Paul Bischoff.

Third Row: Jason Taft, Kris Klinger, Evan Feldman, Bob Young, Chris Onuska.

Second Row: Head coach Bob Darden, trainer Tammy Ogeltree, Brian Winkler, Paul Mariani, Christian Boniforti, Raul Molina, Rich Dopp, Cory Huttenga, manager Stacey Shingle, assistant coach Mike Milidonis.

First Row: Matt Marsich, Mike Mott, Ben Verrall, Jorge Camacho, Josh Miner, Royce Toni, Seth Rubin.

Development of an economics-based methodology for projecting future pollution problems /

Issued June 1978.

Tokamak experimental power reactor conceptual design /

"August, 1976."