Involvement of central muscarinic receptors in social and nonsocial learning in sheep.

Within 12 h following parturition, ewes develop visual and auditory recognition of their lamb. To investigate whether central cholinergic muscarinic transmission plays a specific role in this social learning, we studied the effects of a muscarinic antagonist on neonate recognition via visual/auditory cues and acquisition of a nonsocial visual discrimination. Injections of scopolamine (100 microg/kg; a muscarinic antagonist crossing the blood-brain barrier) after birth did not affect maternal behavior but impaired visual/auditory recognition of the offspring.

Small for gestational age as a predictor of behavioral and learning problems in twins.

The study examines the effects of being born small for gestational age (SGA) on rates of behavioral problems in twins and siblings, utilising data from the Australian Twin Study of disruptive behavior disorders in twins and their siblings. Participants were 3944 twins and their siblings who were assessed at two intervals three years apart. At the first assessment (1991), they ranged between 4 and 12 years of age.

Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation.

Knowledge of the function of the cell cycle checkpoints in tumour cells may be important to develop treatment strategies for human cancers. The protein p53 is an important factor that regulates cell cycle progression and apoptosis in response to drugs. In human malignant mesothelioma, p53 is generally not mutated, but may be inactivated by SV40 early region T antigen (SV40 Tag).

[Aortic stenosis with left ventricular dysfunction].

Patients affected by aortic stenosis with severe systolic left ventricular dysfunction have a poor spontaneous prognosis. The results of valvular replacement are globally good, at the price of an acceptable operative mortality. The existence of surgical failure has however prompted much work aimed at better definition of prognostic factors and for proposing new methods of specifying surgical indications.

Replication of the latent class structure of Attention-Deficit/Hyperactivity Disorder (ADHD) subtypes in a sample of Australian twins.

Background: Previous efforts to subtype Attention-Deficit/Hyperactivity Disorder (ADHD) using latent class analysis (LCA) applied to DSM-IV symptom profiles of adolescent female twins from Missouri (USA) have identified distinct classes within the domains of inattention, hyperactivity-impulsivity and combined-type problems. The objective of the current report is to determine if the latent class structure of ADHD subtypes can be replicated in a culturally distinct sample of female and male Australian twins.

Method: LCA was applied to parent-report DSM-IV ADHD symptom profiles of N=2,848 child and adolescent Australian twins and compared to North American findings.

Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a).

Receptor tyrosine kinases activate mitogen-activated protein (MAP) kinases through Ras, Raf-1, and MEK. Receptor tyrosine kinases can be transactivated by G protein-coupled receptors coupling to G(i) and G(q). The human G protein-coupled serotonin receptors 5-HT(4(b)) and 5-HT(7(a)) couple to G(s) and elevate intracellular cAMP.

Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma.

Some cancer patients mount spontaneous T- and B-cell responses against their tumor cells. Autologous tumor reactive CD8 cytolytic T lymphocyte (CTL) and CD4 T-cell clones as well as antibodies from these patients have been used for the identification of genes encoding the target antigens. This knowledge opened the way for new approaches to the immunotherapy of cancer.

The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases.

The proteasome produces MHC class I-restricted antigenic peptides carrying N-terminal extensions, which are trimmed by other peptidases in the cytosol or within the endoplasmic reticulum. In this study, we show that the N-terminal editing of an antigenic peptide with a predicted low TAP affinity can occur in the cytosol. Using proteomics, we identified two cytosolic peptidases, tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, that trimmed the N-terminal extensions of the precursors produced by the proteasome, and led to a transient enrichment of the final antigenic peptide.

A recyclable assay to analyze the NH(2)-terminal trimming of antigenic peptide precursors.

The proteasome plays an essential role in the production of MHC class I-restricted antigenic peptides. Recent results have indicated that several peptidases, including tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, could act downstream of the proteasome by trimming NH(2)-terminal extensions of antigenic peptide precursors liberated by the proteasome. In this study, we have developed a solid-phase peptidase assay that allowed us to efficiently purify and immobilize proteasome, tripeptidyl peptidase II, and puromycin-sensitive aminopeptidase.

Project for a scientific psychiatry in the 21st century.

Objective: To discuss potential advances in neuroscientific knowledge in the 21st century, enabling the realization of Freud's original vision of a basic biological science and an associated metapsychology.

Results: The Australian Twin Study of Attention Deficit Hyperactivity Disorder (ADHD) has demonstrated the high heritability of the core symptoms of ADHD, as well as showing important genetic and environmental influences on comorbid conditions. Brain mapping techniques suggest that working memory, as measured by an A-X Continuous Performance Task, is important in ADHD.

Responses to soils and a test for preadaptation to serpentine in Phacelia dubia (Hydrophyllaceae).

•  Tests for adaptation to three different soils inhabited by subspecific taxa within Phacelia dubia and for preadaptation to a serpentine soil were conducted to examine the plausibility of an endemic-to-endemic evolutionary pathway. Each taxon performed optimally on its home soil, demonstrating edaphic specialization. None survived on the serpentine.

Neurobiological mechanisms involved in recognition of olfactory signature of the young in sheep.

The following review focuses on neurobiological mechanisms responsible for the individual recognition of the olfactory signature of the young by the ewe at parturition. Steroids and vaginocervical stimulation are responsible for neurochemical and electrophysiological changes within the olfactory bulb that are part of the learning mechanisms of the individual lamb odour, thus allowing the establishment of a selective bond between the ewe and her lamb. There is an increase in the number of mitral cells, the principal cells of the olfactory bulb that respond to lamb odours, which is associated with increased release of glutamate and gamma-aminobutyric acid from the dendrodendritic synapses between the mitral and granule cells.

Twenty-four-hour-old lambs rely more on maternal behavior than on the learning of individual characteristics to discriminate between their own and an alien mother.

Lambs can discriminate their own mother from an alien dam on the first day of life, suggesting the recognition of individual physical characteristics of the mother. Alternatively, their choice may depend on behavioral differences existing between the ewes because of their maternal selectivity. To clarify this, the ability of 24-hr-old lambs to discriminate between their own and an alien mother, that were either intact and accept only their own lamb at nursing (i.

Molecular genetics of ADHD: prospects for novel therapies.

Attention deficit hyperactivity disorder has been shown to be a highly heritable disorder, leading to an increasing interest in genetic studies. While multiple genes may be involved, the candidate gene approach is based on postulated neurotransmitter mechanisms. Molecular genetic advances in relation to dopaminergic (dopamine transporter, dopamine D4 receptor and dopamine D5 receptor) genes, adrenergic, serotonergic and nicotinic receptor genes are reviewed.

Kinetics of capillary condensation in nanoscopic sliding friction.

The velocity and humidity dependence of nanoscopic sliding friction has been studied on CrN and diamondlike carbon surfaces with an atomic force microscope. The surface wettability is found to be decisive. Partially hydrophilic surfaces show a logarithmic decrease of friction with increasing velocity, the slope of which varies drastically with humidity, whereas on partially hydrophobic surfaces we confirm the formerly reported logarithmic increase.

Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae.

We have investigated the localization and function of the epidermal growth factor receptor (EGFR) in normal cells, in cholesterol-depleted cells and in cholesterol enriched cells. Using immunoelectron microscopy we find that the EGFR is randomly distributed at the plasma membrane and not enriched in caveolae. Binding of EGF at 4 degrees C does not change the localization of EGFR, and by immunoelectron microscopy we find that only small amounts of bound EGF localize to caveolae.

The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome.

By stimulating human CD8(+) T lymphocytes with autologous dendritic cells infected with an adenovirus encoding MAGE-3, we obtained a cytotoxic T lymphocyte (CTL) clone that recognized a new MAGE-3 antigenic peptide, AELVHFLLL, which is presented by HLA-B40. This peptide is also encoded by MAGE-12. The CTL clone recognized MAGE-3--expressing tumor cells only when they were first treated with IFN-gamma.

Proteasome-assisted identification of a SSX-2-derived epitope recognized by tumor-reactive CTL infiltrating metastatic melanoma.

The tumor Ag SSX-2 (HOM-MEL-40) was found by serological identification of Ags by recombinant expression cloning and was shown to be a cancer/testis Ag expressed in a wide variety of tumors. It may therefore represent a source of CD8(+) T cell epitopes useful for specific immunotherapy of cancer. To identify potential SSX-2-derived epitopes that can be recognized by CD8(+) T cells, we used an approach that combined: 1) the in vitro proteasomal digestion of precursor peptides overlapping the complete SSX-2 sequence; 2) the prediction of SSX-2-derived peptides with an appropriate HLA-A2 binding score; and 3) the analysis of a tumor-infiltrated lymph node cell population from an HLA-A2(+) melanoma patient with detectable anti-SSX-2 serum Abs.