The Glypicans

Summary: Proteoglycans, produced by most eukaryotic cells are versatile components of pericellular and extracellular matrix. They are composed of protein core to which one or more glycosamino-glycan (GAG) chains are attached. One of few families of proteoglycans are glypicans. All glypicans share similar features as core protein of 60 kDa, 14 conserved cysteine residues, a special region localized near the plasma membrane, containing 2 or more Ser-Gly sequences for GAG attachment, hydrophobic C- and N-terminal parts of core protein similar to signal peptide, as well as linkage with external leaflet of the plasma membrane via a glycosylpho-sphatidylinositol. The glypicans  are implicated in cell division, adhesion, migration and modulation of growth factor activities. Mutation in glypicans may cause few congenital diseases and premature death.

Key words: proteoglycans, glypicans

Biochemical and Molecular Aspects - of Leaf Senescence

Summary: Senescence is a developmental stage of the plant life cycle, leading to the death of specific cells, organs for instance leaves, or whole organisms. Initiation of the leaf senescence and its normal process require expression of many specific genes, called senescence-associated genes � sags. Different senescence-enhanced genes encoding degradative enzymes such as: proteases, nucleases, also enzymes involved in lipid and carbohydrate metabolism, enzymes involved in nitrogen mobilization, were identified. Significant chromatin condensation, non-random, internucleosomal fragmentation of nuclear DNA (nDNA) and enhanced expression of genes, of which products are specific cysteine proteases in senescing mesophyll prove, that leaf senescence is genetically defined process involving mechanisms of the programmed cell death (PCD).

Key words: cysteine proteases, internucleosomal fragmentation of nuclear DNA, leaf senescence, mesophyll, programmed cell death (PCD), sags genes  

Signal Functions of ATP in the Central Nervous System

Summary: ATP cooperating with the P2 purinoceptors plays a role of neurotransmitter in the CNS. Both types of these purinoceptors (P2X and P2Y) are present in CNS. These receptors are found in all structures of the brain, but the P2X to P2Y ratio is characteristic for every structure. This ratio might change during the development and maturation of the brain structures. The special role in CNS is played by P2X purinoceptors, which are the ion channels characterized by low selectivity and fast transmission. On the other hand, the action of P2Y purinoceptors is mediated by the G proteins. The function of P2Y is connected to the activation of the intracellular second messengers. The sequence comparison of cloned P2 purinoceptors has revealed the differences not only between P2X and P2Y types, but also between members of this groups. The enzymes belonging to the E-NTPDase family play the special role in the ATP mediated neurotransmission. They break the signal and co-operate with 5'-nucleotidase in generation of other neurotransmitters. The antagonistic action of substrates and products of the chain of these enzymatic reactions suggests that the cell metabolism would depend on the [ATP]/[Ado] ratio. 

Key words: ATP, ecto-enzymes, ecto-apyrase, ecto-ATPase, E-NTPDase, purinoceptors P2, P2X receptor, P2Y receptor

Dendritic Cells for Immunotherapy

Summary: Dendritic cells are professional antigen-presenting cells. They are found in the skin, blood, lymph nodes and other organs. Two their subpopulations are present in an organism � myeloblastic and lymphoblastic, and this is the only example that we know. Dendritic cells play a key role in immunological response. The clinical and experimental studies suggest their use in tumor treatment, viral infections and autoimmunological disorders. In this review the biology of dendritic cells, their physiology, in vitro culturing methods and clinical use is described.

Key words: antigen-presenting cells, dendritic cells, immunotherapy

Embrion Spatial Differentiation Mechanisms

Summary: Te overall body plan of the organism is laid down during oogenesis, and in early embryogenesis. In many types of eggs some specific factors (determinants) are symmetrically deposited within these cells what results thereafter in differential mitoses of embryos. The overall body plan of embryo results from a hierarchy and spatially self-limiting activations of fairly universal classes of genes coding some transcription factors essential for pattern formation in different types of embryos, and from activations of genes controlling the geometry of cleavage. Implementation of instructions concerning the emergence of the body plan specificies the main anteroposterior and dorso-ventral reference axes and the proportional assessment of the primary regionalization of embryos. Two kinds of mechanisms creating positional information are presented: 1) based on cross-talks of signalling pathways either among particular cells within the embryos, or between the embryo and adjacent somatic cells of the ovary, and 2) based on mechanism polarising and orienting mitoses. The emergence of positional information within the embryos is discussed in terms of appearance of gradients of morphogens, the primary embryonal induction, lateral inhibition and mechanisms of segmentation. The recent idea of evolution of homeotic genes by their tandem duplications and diversification is summarized, that results in combinatory networks of the homeotic genes, monitoring specification of the body parts.

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Mechanisms of Interleukin 1 Signal Transduction

Summary: Interleukin 1 (IL-1) is one of the major proinflammatory cytokines responsible for the regulation of immune and inflammatory response. In this paper we present up-to date information concerning the mechanisms of intracellular signal transduction induced by this cytokine. Interleukin 1 effects on target cells are mediated via membrane receptors. One of them (type I) is responsible for interleukin 1 intracellular signaling, whereas the other (type II) is a natural regulator of the cytokine activity. Interleukin 1 receptors belong to a large superfamily of proteins showing similarities either in intra- or extracellular domains. A group of highly conserved  Toll proteins has  been distinguished within this superfamily; these proteins play important roles in immune systems of various organisms, from plants to a man. Interaction of interleukin 1 with its type I receptor leads to the association of adaptor proteins with the receptor, and in turn to the formation of receptor complex which initiates signaling pathways. One of the major pathways of intracellular signal transduction of interleukin 1 leads to mobilization of the transcription factor NF-kB. NF-kB is necessary for transcription initiation of almost all genes, which  products  participate in inflammatory response. Activation of other transcription factors by interleukin 1 is often mediated by protein kinases of MAP kinase family. In spite of recent achievements in clarifying the IL-1 signaling mechanisms, still there is a need for intense research on interactions between distinct signaling pathways and their significance for different activities of interleukin 1.

Key words: interleukin 1, IL-1 receptors, signal transduction, transcription factor NF-kB, MAP kinases
 

Detection of Intracellular Cytokines by Flow Cytometry: Application and Problems

Summary: Cytokines are proteins regulating the development and duration of normal and pathological immune response. They are responsible for the transduction of informations among immune system cells and are involved in the communication between the immune and neuroendocrine  systems. Cytokines play roles in the immune response, hematopoiesis, apoptosis, inflammation and homeostasis. Distinct lymphocyte populations are characterized by the spectrum of synthesized cytokines and their production may be altered in diseases. Analysis of cytokines expression may be helpful in the evaluation of functional status of the immune system. Flow cytometry is the method of choice for the analysis of single cells. Antigens can be detected with specific fluorochrome-labeled antibodies on the cell surface and within the cells, after fixation and permeabilization of the cell membrane. This method offers a wide range of  research possibilities, but also creates problems.

Keywords: lymphocyte, intracellular cytokines, flow cytometry

Nobel Prize 2000 in Medicine and Physiology for the Studies on the Signal Transduction in the Nervous System

Summary: Nobel laureates '2000 in Physiology and Medicine were Arvid Carlsson, Paul Greengard, and Eric Kandel. Their discoveries have been crucial for our understanding of the mechanisms of signal transduction inside and between nerval cells. Carlsson discovered that dopamine is a neurotransmitter � the substance, which actively takes part in the signal transduction in synapses. He showed that its depletion results in movement dysfunction similar to one observed in Parkinson's disease. The symptoms could be treated with the dopamine precursor: L-dopa. Greengard showed that neurotransmitter, when bound to its specific membrane receptor, turns on the cascade of processes which lead to long-lasting changes in the functioning of the nerve cell. He also provided evidence that phosphorylation of proteins is an important way to change their function and that this phenomenon is not only common in the cell but also crucial for its physiology. Describing the function of DARP-32 protein � the phosphatase-1 inhibitor, he proposed the model according to which DARP-32 could serve as a modulator of the influences of dopamine on other neurotransmitters, i.g., glutamate. Eric Kandel built the molecular model of the changes, in a presynaptic neuron and synapse, which occur during the formation of short- and long-term memory traces. According to Kandel during short-term memory formation some proteins are transiently phosphorylated, wheras the formation of long-term memory demands synthesis of new proteins, changes in gene expression and is followed by morphological changes of neuronal connections.

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