In this study, we investigated the ability of NAN-190 to potentiate the circadian rhythm response to light as measured by phase of behavioral activity rhythms. NAN-190 (5 mg/kg, GANT61 cost i.p.) was able to significantly potentiate the response to light both in dark-adapted and entrained hamsters. Furthermore, NAN-190 was effective even when administered up to 6 h after light onset. Response to a light pulse was both greater in magnitude and involved fewer unstable transient cycles. Finally, NAN-190 was able to speed re-entrainment to a 6 h advance of the light/dark cycle by an average of 6 days when compared with vehicle-treated animals. This work suggests that compounds like

NAN-190 may hold great potential as a pharmaceutical treatment for jetlag, shift

work, and other circadian disorders. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Mismatching for human leukocyte antigen (HLA)-DPB1 in unrelated donor hematopoietic stem cell transplantation (URD-SCT) has been associated with a decreased click here risk of disease relapse, indicating that HLA-DP may represent a target for graft-versus-leukemia (GVL) reactivity in HLA class II-expressing hematological malignancies. To investigate whether HLA-DP-specific T cells could mediate GVL reactivity following HLA-DPB1-mismatched URD-SCT and donor lymphocyte infusion (DLI), we analyzed the immune response in a patient with leukemic lymphoplasmacytic lymphoma Diflunisal responding to DLI without graft-versus-host disease. The emergence of leukemia-reactive CD4+ T cells during the clinical immune response was demonstrated by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) analysis. Following clonal isolation of these leukemia-reactive CD4+ T cells, blocking studies, panel studies and retroviral transduction experiments of both mismatched HLA-DPB1 alleles identified HLA-DPB1*0201 and HLA-DPB1* 0301 as the targets of this immune response. The HLA-DPB1-specific CD4+ T-cell clones were capable of recognizing and lysing several HLA-DP-expressing myeloid

and lymphoid hematological malignant cells. Since HLA-DP expression is mainly restricted to hematopoietic cells, HLA-DP may be used as a specific target for immunotherapy following T-cell-depleted URD-SCT. Therefore, in patients with HLA class II-expressing hematological malignancies HLA-DP-mismatched SCT may be preferable over fully matched SCT allowing DLI to induce a GVL effect.”
“The orbitofrontal cortex (OFC) plays a critical role in learning a reversal of stimulus-reward contingencies. Dopamine (DA) neurons probably support reversal learning by emitting prediction error signals that indicate the discrepancy between the actually received reward and its prediction. However, the role of DA receptor-mediated signaling in the OFC to adapt behavior to changing stimulus-reward contingencies is largely unknown.