Normal human aging and early-stage schizophrenia share common molecular profiles.

We examined genome-wide expression datasets from human prefrontal cortex of normal and schizophrenic individuals ranging from 19 to 81 years of age. We found that changes in gene expression that are correlated with aging in normal subjects differ dramatically from those observed with aging in schizophrenic subjects. Only 2.

Increased expression of monocyte CD44v6 correlates with the deveopment of encephalitis in rhesus macaques infected with simian immunodeficiency virus.

In people infected with human immunodeficiency virus type 1 (HIV-1), the accumulation of macrophages in the brain correlates with encephalitis and dementia. We hypothesized that a pattern of surface marker expression in blood monocytes may serve as a marker for central nervous system (CNS) disease. Using the simian immunodeficiency virus (SIV)-rhesus monkey model, we analyzed functionally relevant surface markers on monocytes and macrophages from the blood and brain in animals that did or did not develop SIV encephalitis.

Effects of simian immunodeficiency virus on the circadian rhythms of body temperature and gross locomotor activity.

In monkeys infected with simian immunodeficiency virus (SIV), changes in body temperature and locomotor activity occur after the acute retroviral syndrome stage of the disease. However, alterations to the circadian rhythm of these factors in SIV-infected monkeys have not been reported. To determine whether the circadian rhythm of body temperature and locomotor activity are disrupted during SIV infection, we analyzed the temperature and activity patterns of SIV-infected monkeys through different stages of the disease, progressing to SIV encephalitis by using the cosinor model for circadian oscillation.

Fc receptor but not complement binding is important in antibody protection against HIV.

Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine. Indeed, passively administered neutralizing antibodies have been shown to protect against HIV challenge in some of the best available animal models. For example, antibodies given intravenously can protect macaques against intravenous or mucosal SHIV (an HIV/SIV chimaera) challenge and topically applied antibodies can protect macaques against vaginal SHIV challenge.

Activation of murine CD4+ and CD8+ T lymphocytes leads to dramatic remodeling of N-linked glycans.

Differentiation and activation of lymphocytes are documented to result in changes in glycosylation associated with biologically important consequences. In this report, we have systematically examined global changes in N-linked glycosylation following activation of murine CD4 T cells, CD8 T cells, and B cells by MALDI-TOF mass spectrometry profiling, and investigated the molecular basis for those changes by assessing alterations in the expression of glycan transferase genes. Surprisingly, the major change observed in activated CD4 and CD8 T cells was a dramatic reduction of sialylated biantennary N-glycans carrying the terminal NeuGcalpha2-6Gal sequence, and a corresponding increase in glycans carrying the Galalpha1-3Gal sequence.

Host response and dysfunction in the CNS during chronic simian immunodeficiency virus infection.

CNS abnormalities can be detected during chronic human immunodeficiency virus (HIV) infection, before the development of opportunistic infections or other sequelae of immunodeficiency. However, although end-stage dementia caused by HIV has been linked to the presence of infected and activated macrophages and microglia in the brain, the nature of the changes resulting in the motor and cognitive disorders in the chronic stage is unknown. Using simian immunodeficiency virus-infected rhesus monkeys, we sought the molecular basis for CNS dysfunction.

Susceptibility of Chinese rhesus monkeys to SIV infection.

The use of China-derived monkeys in AIDS research has been limited by reports of reduced susceptibility to SIV. We performed a serial passage of SIV in Chinese macaques, which resulted in a viral stock capable of inducing simian AIDS and high levels of replication in these animals. Similar to HIV in humans, SIV pathogenesis in non-human primates is not limited by geographical origin.

De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years.

We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure and gene expression. Sixty-one kidney recipients treated with basiliximab mycophenolate mofetil (MMF) and prednisone (P) were randomly assigned to concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays.