Activation of metabotropic glutamate 5 and NMDA receptors underlies the induction of persistent bursting and associated long-lasting changes in CA3 recurrent connections.

The aim of this study was to describe the induction and expression mechanisms of a persistent bursting activity in a horizontal slice preparation of the rat limbic system that includes the ventral part of the hippocampus and the entorhinal cortex. Disinhibition of this preparation by bicuculline led to interictal-like bursts in the CA3 region that triggered synchronous activity in the entorhinal cortex. Washout of bicuculline after a 1 hr application resulted in a maintained production of hippocampal bursts that continued to spread to the entorhinal cortex.

Determination of group I metabotropic glutamate receptor subtypes involved in the frequency of epileptiform activity in vitro using mGluR1 and mGluR5 mutant mice.

In mouse hippocampal slices, bicuculline elicited spontaneous epileptiform bursts with a duration of 200-300 ms and with a frequency of five to six events per minute. Application of group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG) increased the burst frequency up to 300% at concentrations of 50 to 100 microM, while it decreased the burst duration below 100 ms. In slices of subtype I mGluR1 or subtype I mGluR5 knockout mice, bicuculline elicited spontaneous epileptiform bursts with similar duration and frequency as those measured in wild-type mice but without the previous effects seen following application of DHPG at concentrations up to 100 microM.

Insulin-secreting beta-cell dysfunction induced by human lipoproteins.

Diabetes is associated with significant changes in plasma concentrations of lipoproteins. We tested the hypothesis that lipoproteins modulate the function and survival of insulin-secreting cells. We first detected the presence of several receptors that participate in the binding and processing of plasma lipoproteins and confirmed the internalization of fluorescent low density lipoprotein (LDL) and high density lipoprotein (HDL) particles in insulin-secreting beta-cells.

The mif gene is transcriptionally regulated by glucose in insulin-secreting cells.

Macrophage migration inhibitory factor (MIF) is an important regulator of glucose homeostasis. In pancreatic beta-cells, MIF expression is regulated by glucose and its secretion potentiates the glucose-induced insulin secretion. The molecular mechanisms by which glucose mediates its effect on MIF expression are not elucidated.

Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments.

MEKK1, a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase, generates anti-apoptotic signaling as a full-length protein but induces apoptosis when cleaved by caspases. Here, we show that caspase-dependent cleavage of MEKK1 relocalizes the protease-generated 91-kDa kinase fragment from a particulate fraction to a soluble cytoplasmic fraction. Relocalization of MEKK1 catalytic activity is necessary for the pro-apoptotic function of MEKK1.

Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosis.

Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) kinases (MEKKs) are serine/threonine kinases that are upstream regulators of MAPKs. Here, the role of the amino-terminal (N-terminal) domain of MEKK1-4 on the regulation of different intracellular signaling pathways, apoptosis, and cell proliferation has been assessed by comparing the responses induced by the full-length (FL) MEKKs to those induced by the kinase domains only. For each MEKK, the pattern of activation of NF kappa B, the ERK MAPK pathway, and the c-Jun N-terminal kinase (JNK) MAPK pathway markedly differed between the kinase domain and the FL form.

EEG coherence studies in the normal brain and after early-onset cortical pathologies.

Visual corpus callosum (CC) preferentially interconnects neurons selective for similar stimulus orientation near the representations of the vertical meridian. These properties allow studying the CC functionality with EEG coherence analysis. Iso-oriented and orthogonally-oriented gratings were presented to the two hemifields, either close to the vertical meridian or far from it.

Islet-brain1/JNK-interacting protein-1 is required for early embryogenesis in mice.

Islet-brain1/JNK-interacting protein-1 (IB1/JIP-1) is a scaffold protein that organizes the JNK, MKK7, and MLK1 to allow signaling specificity. Targeted disruption of the gene MAPK8IP1 encoding IB1/JIP-1 in mice led to embryonic death prior to blastocyst implantation. In culture, no IB1/JIP-1(-/-) embryos were identified indicating that accelerated cell death occurred during the first cell cycles.

Methylene blue-fast green staining of hemopoietic colonies in agar cultures.

A simple technique is described for the routine in situ identification of the cellular composition of colonies and clusters in agar cultures of hemopoietic cells. The entire culture, dried and formalin vapor fixed within a Petri dish, is stained with a mixture of methylene blue and fast green. By this method cellular ribonucleoproteins (RNP), deoxyribonucleoproteins (DNP) and some cationic (arginine and lysine containing) proteins are detected.