Damage to the fronto-polar cortex is associated with impaired multitasking.

Background: A major question in understanding the functional organization of the brain is to delineate the functional divisions of the prefrontal cortex. Of particular importance to the cognitive capacities that are uniquely human is the fronto-polar cortex (Brodmann's area 10), which is disproportionally larger in humans relative to the rest of the brain than it is in the ape's brain. The specific function of this brain region remains poorly understood, but recent neuroimaging studies have proposed that it may hold goals in mind while exploring and processing secondary goals.

Experimental approaches for the study of oxytocin and vasopressin gene expression in the central nervous system.

Intron-specific probes measure heteronuclear RNA (hnRNA) levels and thus approximate the transcription rates of genes, in part because of the rapid turnover of this intermediate form of RNA in the cell nucleus. Previously, we used oxytocin (Oxt)- and vasopressin (Avp)- intron-specific riboprobes to measure changes in Oxt and Avp hnRNA levels in the supraoptic nucleus (SON) by quantitative in situ hybridization (ISH) after various classical physiological perturbations, including acute and chronic salt loading, and lactation. In the present experiments, we used a novel experimental model to study the neurotransmitter regulation of Oxt and Avp gene expression in the rat SON in vivo.

[Neural substrates underlying cognitive expertise].

Recent behavioral and neuro-anatomical studies of cognitive expertise have suggested that that superior performance in memory experts is neither due to extraordinary general intelligence nor anatomical brain difference. Furthermore, functional neuro-imaging studies have revealed that expert performance in mental abacus and memory experts is not attributable to increased brain activities of the process that exists in non-experts or to hyper-activity in the prefrontal cortex. On the contrary, cognitive experts utilize brain areas that are not used by non-experts.

Imaging the spatiotemporal organization of neural activity in the developing spinal cord.

In this review, we discuss the use of imaging to visualize the spatiotemporal organization of network activity in the developing spinal cord of the chick embryo and the neonatal mouse. We describe several different methods for loading ion- and voltage-sensitive dyes into spinal neurons and consider the advantages and limitations of each one. We review work in the chick embryo, suggesting that motoneurons play a critical role in the initiation of each cycle of spontaneous network activity and describe how imaging has been used to identify a class of spinal interneuron that appears to be the avian homolog of mammalian Renshaw cells or 1a-inhibitory interneurons.

CXCR4/SDF-1 system modulates development of GnRH-1 neurons and the olfactory system.

Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 influence neuronal migration and have been identified in nasal regions. Gonadotropin releasing hormone-1 (GnRH-1) neurons migrate from nasal regions into the developing forebrain, where postnatally they control reproduction. This study examined the role of SDF-1/CXCR4 in development of the GnRH-1/olfactory systems.

Temporal migration of gonadotrophin-releasing hormone-1 neurones is modified in GAD67 knockout mice.

Gonadotrophin-releasing hormone (GnRH-1) neurones reside in the forebrain and regulate gonadal function via the hypothalamic-pituitary-gonadal axis. Disruption of this axis results in reproductive dysfunction. During embryonic development, GnRH-1 neurones migrate from the nasal pit through the nasal/forebrain junction (NFJ) into the developing brain.

MITF and cell proliferation: the role of alternative splice forms.

Recent studies show that the melanocyte transcription factor MITF not only activates differentiation genes but also genes involved in the regulation of the cell cycle, suggesting that it provides a link between cell proliferation and differentiation. MITF, however, comes in a variety of splice isoforms with potentially distinct biological activities. In particular, there are two isoforms, (-) and (+) MITF, that differ in six residues located upstream of the DNA binding basic domain and show slight differences in the efficiency with which they bind to target DNA.

Syneretic response to incremental pressures in calf lenses.

Purpose: Syneretic response to pressure variation of 1 atm or more has been demonstrated previously in bovine and human lenses with nuclear magnetic resonance (NMR) relaxation measurements. This study is designed to prove that a similar response is observable in smaller pressure increments closer to the normal physiological range.

Methods: Excised calf eyes were enucleated, the lenses dissected out, and immersed in medium.

Dissociating the roles of the rostral anterior cingulate and the lateral prefrontal cortices in performing two tasks simultaneously or successively.

A fundamental question about the nature of cognitive control is whether performing two tasks successively or simultaneously activates distinct brain regions. To investigate this question, we designed a functional magnetic resonance imaging (fMRI) study that compared task-switching and dual-task performance. The results showed that performing two tasks successively or simultaneously activated a common prefronto-parietal neural network relative to performing each task separately.

The roles of timing and task order during task switching.

The neural bases of the different processes involved in task switching remain poorly identified. Whether distinct brain regions are involved according to the overall structure of the task sequence and the predictability of task timing during task switching is unknown. To address this question, we used functional magnetic resonance imaging and a 2 x 2 factorial design varying timing (fixed/random) and task order (predictable/unpredictable).

MAP kinase signaling cascade dysfunction specific to Alzheimer's disease in fibroblasts.

Mitogen-activated protein kinases (such as Erk1/2) regulate phosphorylation of the microtubule-associated protein tau and processing of the amyloid protein beta, both events critical to the pathophysiology of Alzheimer's disease (AD). Here we report that enhanced and prolonged Erk1/2 phosphorylation in response to bradykinin (BK) was detected in fibroblasts of both familial and sporadic AD, but not age-matched controls (AC). The AD-associated abnormality in Erk1/2 phosphorylation was not seen in fibroblasts from Huntington's disease patients with dementia.

The roles of the cerebellum and basal ganglia in timing and error prediction.

Recent evidence that the cerebellum and the basal ganglia are activated during the performance of cognitive and attention tasks challenges the prevailing view of their primary function in motor control. The specific roles of the basal ganglia and the cerebellum in cognition, however, have been difficult to identify. At least three functional hypotheses regarding their roles have been proposed.

Combinatorial peptide libraries and biometric score matrices permit the quantitative analysis of specific and degenerate interactions between clonotypic TCR and MHC peptide ligands.

The interaction of TCRs with MHC peptide ligands can be highly flexible, so that many different peptides are recognized by the same TCR in the context of a single restriction element. We provide a quantitative description of such interactions, which allows the identification of T cell epitopes and molecular mimics. The response of T cell clones to positional scanning synthetic combinatorial libraries is analyzed with a mathematical approach that is based on a model of independent contribution of individual amino acids to peptide Ag recognition.

Dissociating the role of the medial and lateral anterior prefrontal cortex in human planning.

The anterior prefrontal cortex is known to subserve higher cognitive functions such as task management and planning. Less is known, however, about the functional specialization of this cortical region in humans. Using functional MRI, we report a double dissociation: the medial anterior prefrontal cortex, in association with the ventral striatum, was engaged preferentially when subjects executed tasks in sequences that were expected, whereas the polar prefrontal cortex, in association with the dorsolateral striatum, was involved preferentially when subjects performed tasks in sequences that were contingent on unpredictable events.

Defective HIV-1 provirus encoding a multitarget-ribozyme inhibits accumulation of spliced and unspliced HIV-1 mRNAs, reduces infectivity of viral progeny, and protects the cells from pathogenesis.

A HeLa T4 cell line containing a defective human immunodeficiency virus type 1 (HIV-1) DNA (HD4) was isolated. After transactivation with Tat, the HD4 DNA was transcribed into a single 3.7-kb mRNA that encodes a chimeric CD4/Env protein and a multitarget-ribozyme directed against multiple sites within the gp120 coding region of HIV-1 RNA (Chen et al.

Selection of retrovirally transduced cells to enhance the efficiency of gene therapy.

Retrovirally mediated gene transfer is the approach of choice for many laboratories interested in gene therapy. One problem, however, is that the efficiency of therapeutic gene transfer to some important target cells is low. A strategy employed by a number of investigators to overcome this shortcoming is to construct recombinant viruses that employ selection modalities.

Abnormalities of p16, p15 and CDK4 genes in recurrent malignant astrocytomas.

Abnormalities in the p16, p15 and CDK4 genes that regulate transition through the G1 phase of the cell cycle have been implicated in the malignant progression of astrocytomas. The results of the present study demonstrate that dysfunction of these genes also occurs during recurrence of glial tumors that were highly malignant at first presentation. Analysis of 10 matched pairs of high grade malignant astrocytomas and their subsequent recurrences identified three distinct groups.

Cerebral white matter in the centrum semiovale exhibits a larger N-acetyl signal than does gray matter in long echo time 1H-magnetic resonance spectroscopic imaging.

Long echo time (272 ms) 1H magnetic resonance spectroscopic imaging was used to measure the relative magnitudes of the N-acetylaspartate (NAA) signal in a variety of anatomically defined brain structures (centrum semiovale, thalamus, medial frontal cortex, and genu of the corpus callosum) composed primarily of gray matter or white matter. Six normal young adult humans aged 30-40 were studied. With a 95% level of statistical confidence, the white matter in the centrum semiovale (CSO) produced a more intense NAA signal than did the gray matter in the thalamus and the frontal cortex.

NBQX inhibits AMPA-induced locomotion after injection into the nucleus accumbens.

The role of glutamate receptors in locomotor activity was investigated by examining the ability of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX), a non-NMDA antagonist, to inhibit the stimulation of locomotion produced by the activation of various excitatory amino acid receptors in the nucleus accumbens. NBQX inhibited the stimulation of locomotor activity produced by intra-accumbens alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) at doses which had no effect on the locomotion produced by kainate or NMDA. Furthermore, this dose of NBQX had no effect on locomotion when injected alone into this brain region.

Evidence for the involvement of a potential second tumor suppressor gene on chromosome 17 distinct from p53 in malignant astrocytomas.

Molecular analysis of malignant astrocytomas demonstrated three distinct groups of tumors with chromosome 17p abnormalities, which include (a) deletion of the p53 locus (17p13.1) and mutations in the remaining allele, (b) deletion of the p53 locus but no detectable mutations in the remaining allele, and (c) deletions not including the p53 locus but mutations in one of the alleles. Furthermore, deletion mapping analysis demonstrated allelic loss of genes distal to D17S28/D17S5 markers (17p13.