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Biomedical subjects

P Jedlicka

Publications and source records attributed to P Jedlicka.

At least 19 recordsLinked to original sources

Inhibitory transmission, activity-dependent ionic changes and neuronal network oscillations.

Oscillatory network activity arises from interactions between synaptic and intrinsic membrane properties of neurons. In this review, we summarize general mechanisms of synchronous neuronal oscillations. In addition, we focus on recent experimental and computational studies which suggest that activity-dependent changes of ionic environment can affect both the synaptic and intrinsic neuronal properties and influence the network behavior. GABA(A) receptor (GABA(A)R)-mediated signaling, that is based on Cl(-) and HCO(3)(-) permeability, is thought to be important for the oscillogenesis and synchronization in cortical networks. A remarkable feature of GABAergic synapses is that prolonged GABA(A)R activation may lead to switching from a hyperpolarizing to a depolarizing response. This is partly due to a positive shift of the GABA(A) R reversal potential (E(GABA)) that is generated by GABA-induced Cl(-) accumulation in neurons. Recent studies suggest that activity-dependent E(GABA) changes may have important implications for the mechanisms of gamma oscillations and seizure-like discharges. Thus, a better understanding of the impact of intracellular Cl(-) dynamics on network behavior may provide insights into the mechanisms of physiological and pathological brain rhythms. Combination of experiments and simulations is a promising approach for elucidating which properties of the time-varying ionic environment can shape the dynamics of a given circuit.

Biological Clocks↗

Synaptic plasticity, metaplasticity and BCM theory.

In many regions of the brain, the activity-dependent changes in synaptic strength depend on the frequency and timing of presynaptic stimulation and postsynaptic activity (synaptic plasticity), as well as the history of activity at those synapses (metaplasticity). The Bienenstock, Cooper and Munro (BCM) theory made several assumptions about how synapses modify and these have helped to guide various neurobiological and neurocomputational experiments. There does appear to be a good correspondence of the synaptic plasticity and metaplasticity experimental data with the BCM model. (Fig. 1, Ref. 57.).

Action Potentials↗

Multiple functions of Drosophila heat shock transcription factor in vivo.

Heat shock transcription factor (HSF) is a transcriptional activator of heat shock protein (hsp) genes in eukaryotes. In order to elucidate the physiological functions of HSF in Drosophila, we have isolated lethal mutations in the hsf gene. Using a conditional allele, we show that HSF has an essential role in the ability of the organism to survive extreme heat stress. In contrast to previous results obtained with yeast HSF, the Drosophila protein is dispensable for general cell growth or viability. However, it is required under normal growth conditions for oogenesis and early larval development. These two developmental functions of Drosophila HSF are genetically separable and appear not to be mediated through the induction of HSPs, implicating a novel action of HSF that may be unrelated to its characteristic function as a stress-responsive transcriptional activator.

Alleles↗

Characterization of hUCRBP (YY1, NF-E1, delta): a transcription factor that binds the regulatory regions of many viral and cellular genes.

The UCRBP (YY1, delta, NF-E1) protein has been isolated for its ability to bind to the UCR (upstream conserved region) site present in the conserved murine leukemia virus long terminal repeat. UCRBP carries a highly charged N-terminal domain and four C2-H2-type zinc fingers at its C-terminal end. The present study reveals the following results: (i) The UCR site is present in the upstream and/or regulatory regions of numerous mammalian cellular and viral genes to which both recombinant and cellular UCRBP bind. UCR sites are also found in the regulatory regions of repetitive sequences including human LINE-1 elements and mouse intracisternal-A particle sequences. (ii) By immunological and UV cross-linking experiments, we found that two proteins, of approx. 68 kDa and an antigenically related protein of approx. 40 kDa, account for much of the UCR-binding activity in T-lymphocytes. (iii) There is evidence that UCRBP acts as a phosphoprotein. Eight consensus phosphorylation sites are found in the deduced amino-acid sequence of human UCRBP. The cellular UCR-binding activity was abolished by phosphatase treatment, and there is an incremental increase in apparent molecular mass between the cytoplasmic and nuclear forms of the protein, suggesting phosphorylation. (iv) Although UCRBP has been previously shown to act as a transcriptional repressor, we show here that UCRBP can also act as a positive transactivator of a reporter driven by UCR elements when used in co-transfection assays. This transactivation occurred in a dose-restricted manner and was absent at high concentrations of a UCRBP expression plasmid, indicating a complex mode of function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanism of activation of protein synthesis initiation in mitogen-stimulated T lymphocytes.

The pronounced stimulation of protein synthesis in T lymphocytes in response to mitogens is partly due to increased cell size and hence ribosome number. There is also a large increase in translation rate per ribosome as a result of an increased rate of initiation. In response to mitogen, levels of both eukaryotic initiation factor (eIF)-2 and guanine nucleotide exchange factor, GEF, increase in parallel with ribosomes which is consistent with a general increase in the translational machinery but cannot explain the increase in activity per ribosome. However, as total eIF-2 accumulates, the ratio of phosphorylated eIF-2 alpha (eIF-2(alpha P] to eIF-2 alpha decreases. Further, the levels of eIF-2(alpha P) and GEF in resting T lymphocytes are similar. As eIF-2(alpha P) inhibits GEF by effectively sequestering the exchange factor in an inactive 1:1 complex, the level of GEF available for protein synthesis initiation must be very low in resting cells. Hence, as GEF is synthesized and rises above the level of eIF-2(alpha P), there will be a disproportionate increase in GEF available for initiation compared with the increase in total GEF. This increase in available GEF is probably great enough to support the increase in translation rate per ribosome as well as the increase in ribosome number.

Animals↗

Improved carrier detection of haemophilia A using novel RFLPs at the DXS115 (767) locus.

Two novel restriction fragment length polymorphisms (RFLPs) around the DXS115 (767) locus, detectable with the restriction enzymes MspI, are described. Since DXS115 is closely linked to the factor VIII gene (F8C), the MspI RFLP was employed in haemophilia A carrier detection. The utility of these RFLPs lies in the increased applicability and accuracy of diagnoses carried out in cases where available intragenic markers are uninformative.

Deoxyribonuclease HpaII↗