TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients.', 'The effects of allogeneic umbilical cord-derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC-mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation.', 'Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow-derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients.\Question: Is a CD8 T cell/indoleamine 2,3-dioxygenase axis required for mesenchymal stem cell suppression of human systemic lupus erythematosus?

SOLUTION: We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients.

PROBLEM: Context: To identify molecular features associated with clinico-pathological parameters in renal cell cancer.', 'Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging was employed for a kidney cancer tissue microarray containing tissue samples from 789 patients for which clinical follow-up data were available.', 'A comparison of mass spectrometric signals with clinico-pathological features revealed significant differences between papillary and clear cell renal cell cancer. Within the subgroup of clear cell RCC, statistical associations with tumor stage (seven signals, p<0.01 each), Fuhrman grade (seven signals, p<0.0001 each), and presence of lymph node metastases (10 signals, p<0.01 each) were found. In addition, the presence of one signal was significantly linked to shortened patient survival (p=0.0198).\Question: Does mALDI imaging on tissue microarrays identify molecular features associated with renal cell cancer phenotype?

SOLUTION: Our data pinpoint towards various molecules with potential relevance in renal cell cancer. They also demonstrate that the combination of the MALDI mass spectrometry imaging and large-scale tissue microarray platforms represents a powerful approach to identify clinically-relevant molecular cancer features.

PROBLEM: Context: Peripherally administered oxytocin (OT) has produced antipsychotic drug (APD)-like effects in animal tests that are predictive of APD efficacy. However, these effects have mainly been demonstrated using animal models of schizophrenia-like deficits in prepulse inhibition (PPI) of the startle reflex. Another schizophrenia-relevant abnormality that is the basis of a predictive animal test for APD efficacy is deficient latent inhibition (LI). LI is the normal suppression of a classically conditioned response when the subject is pre-exposed to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (UCS). Conditioned taste aversion (CTA), the normal avoidance of ingesting a food or liquid by animals when its taste is associated with an aversive experience, was used to test whether OT facilitates LI consistent with APDs.', 'Brown Norway rats, known to naturally display attenuated LI, were aversively conditioned on two consecutive exposures to flavored drinking water (0.1% saccharin) by pairing it with malaise-inducing lithium chloride injections. Concurrent with conditioning, rats received subcutaneous OT (0.02, 0.1, 0.5mg/kg) or saline. Some rats were pre-exposed to the flavored water prior to its aversive conditioning (pre-exposed) while others were not (non pre-exposed). Two days after aversive conditioning the amount of flavored water consumed during a 20-min session was recorded.', 'As expected, LI, defined as greater consumption by pre-exposed vs. non pre-exposed rats was only weakly exhibited in Brown Norway rats and OT enhanced LI by reducing CTA in pre-exposed rats in a dose-dependent manner, with the 0.02 mg/kg dose producing the strongest effect.\Question: Does peripherally administered oxytocin modulate latent inhibition in a manner consistent with antipsychotic drugs?

SOLUTION:
The facilitation of LI by OT is consistent with the effects produced by APDs and provides further support for the notion that OT has therapeutic potential for schizophrenia.