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vol. 55
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issue 2
303-318
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Prometalloproteases are activated by serine proteases, MMP-3, leucocytic elastase, furin, furin-like proteases and by membrane-type metalloproteases as well. They form complex with some proMMPs and thus they modify their activation.
EN
Histamine is a physiological mediator which exerts both effector and regulatory functions through its receptors on various cells. The aim of the study was to investigate changes in histamine receptor expression on peripheral blood lymphocytes affected by stimulation with both specific and nonspecific stimuli. Lymphocytes were obtained from both healthy and allergic subjects. Cells were incubated with various allergens (mixed grass pollen, Lolium perenne, Dermatophagoides pteronyssinus 1, bee venom, phospholipase A2) and nonspecific (fMLP, PMA/ionomycin, LPS) stimuli. The percentage of histamine-binding cells was determined with a fluorescence microscope after incubation with histamine-fluorescein. In control subjects histamine binding after stimulation with allergens was not significantly changed. In contrast, in allergic subjects stimulation with specific allergens resulted in significantly increased histamine binding. Nonspecific stimulation caused increased histamine binding to lymphocytes in both allergic subjects and healthy controls. We conclude that specific and nonspecific activation of lymphocytes is associated with increased expression of histamine receptors.
EN
Activation of the innate immune system is a prerequisite for the maturation of dendritic cells (DC) and macrophages (M?) followed by clonal expansion of the lymphocytes, targeting cells expressing 'non-self' angitens. Microbes usually have a component competent to active DC/M? for antigens presentation. This component has been colled adjuvant, but recently renamed pathogen-associated molecular pattern (PAMP) or modulin based on its molecular identification. Here, we propose the hypothesis that DC/M? express two sorts of receptors for PAMP, whose signaling pathways lead to a sufficient antigen (Ag)-presenting state. In bacterial infection, a Toll-like receptor (TLR) and an uptake receptor participate in DC maturation and M? activation. Likewise, with a number of viruses, two of the receptors with short consensus repeats (SCR), immunoglobulin-like domains or chemokine receptor-like motifs etc. induce functional modulation of DC/M?. In immune therapy for cancer, primary activation of the innate system would be essential for tumor Ag-specific T cell augmentation. Cancer cells express tumor-associated Ag but barely co-express PAMP, which situation does not allow for the activation of innate immune responses. Supplementing tumor-associated Ag with PAMP may be an effective therapy for patients with cancer. Here, we discuss the possibility of an innate immune therapy for cancer with references to bacillus Culmet guillen cell-wall skeleton (GCG-CWS).
EN
The secretion of interleukin (IL)-2 is a key event in T cell activation. IL-2 allows T cells to enter into the S phase of the cell cycle and divide. After the activation phase takes place, T lymphocytes proliferate and differentiate to generate effector T cells. Thereby, T helper (Th) precursor cells, which are functionally immature, may become Th1 or Th2 effector cells. These subsets are responsible for cell-mediated immunity and humoral responses, respectively. Both, T cell activation and Th differentiation are processes that depend on changes in the pattern of gene expression. The expression and changes in the genes responsible for these events are regulated by transcription factors. This review will focus on both transcription factors involved in the control of IL-2, as well as those that are key in T helper differentiation.
EN
In the last two decades T cell function has been analyzed in vitro from many different angles with a great deal of attention dedicated to the basic requirements of activation. During this time a compendium of information has been collected and has proven to be invaluable. Paradoxically very little is known about T cell activation and function in vivo. In the last decade a number of models have been developed which allow the tracking of Ag-activated T cells in vivo and these studies have been instrumental in advancing the field of T cell biology. In particular, a new and emerging paradigm of T cell immunity is evolving.
EN
Co-variation between subjectively estimated mood/activation and EEG characteristics, based on spectral power parameters, was investigated. Subjective estimation of mood was made by using Thayer's Activation-Deactivation Adjective Checklist, which yielded two dimensions: Energy-Tiredness (with Energy pole having positive valence connotation) and Tension-Calmness (negative connotation for Tension). A within-subject design with two sessions of EEG recording immediately followed by mood assessment was applied. These were separated by a cognitive task, introduced in order to modify the subjects' mood. The correlations between changes in mood estimation and changes in EEG spectral power parameters were calculated. Both ADACL dimensions co-varied with EEG in a specific way according to frequency and localization. Subjective estimation of Energy correlated negatively with alpha1 and, surprisingly, positively with delta, theta1 as well as theta2 relative power. Estimation of Tension correlated positively with theta1 and beta1, and negatively with alpha2 relative power. Presented results suggest that the adjective description of mood has objectively-measurable brain correlates in the EEG.
EN
The functional characterization and subsequent purification of T cell growth factor/interleukin (IL)-2 in the early 1980s established this secreted protein as a key mediator of immune cell activation and provided the prototype that enabled the discovery of numerous cytokines over the ensuing two decades. While soluble immunoregulatory factors were initially identified functionally as biological activities present in the culture supernatants of activated lymphocytes/monocytes, this methodology shifted radically following the completion of the human genome sequence. Computer-generated structural modeling algorithms have replaced functional assays and biochemical purification as the initial means of discovering new cytokines. To date, a total of 31 interleukins, as well as over a dozen other related hematopoietic factors, have been identified. These cytokines and their receptors may be grouped on the basis of structural homologies as well as by shared ligand and receptor subunits. The challenge now at hand is to define the biological functions of the newly identified cytokines and to elucidate the common and divergent roles of related family members. This point is well illustrated by the IL-12/IL-23/IL-27 family, whose members share ligand and receptor subunits and play somewhat overlapping roles in innate and adaptive immune responses. These three cytokines are not entirely redundant, as they may preferentially activate na?ve or memory T cells, induce discrete T cell cytokine profiles, contribute to distinct stages of host immune responses to infectious agents, and differentially promote autoimmunity. Further elucidation of the unique functions of the IL-12 family members may lead to improved immunodiagnostics and therapies.
EN
Initiation and propagation of the immune response is the result of a series of coordinated cellular and biochemical interactions that lead to the activation of multiple cell types. It is now clear that an optimal immune response requires a precise and rapid communication between different cell subsets. This phenomenon, referred to as cross-talk, is believed to be an essential component of the immune response that provides necessary inflammatory mediators and cytolytic activity for controlling infections and diseases. An example of an effective cooperation between different cell types has been recently illustrated by the finding that specific activation of CD1 restricted natural killer T cells (NK T) can quickly lead to the activation of other subsets of cells such as natural killer (NK) and CD8 T cells.
EN
Nuclear factor kB (NF-kB) is common proinflammatory transcription factor involved in expression of c.a. 300 different genes. It is usually present in the cytosol as an inactive complex and upon activation translocates into the nucleus. The mechanisms of activation of NF-kB are complex and they involve several different signaling pathways and plethora of proteins. In this minireview we describe the main deciphered as well as suggested mechanisms regulating of NF-kB activity
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Brain correlates of right-handedness

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EN
Recent development of neuroimaging techniques has opened new possibilities for the study of the relation between handedness and the brain functional architecture. Here we report fMRI measurements of dominant and non-dominant hand movement representation in 12 right-handed subjects using block design. We measured possible asymmetry in the total volume of activated neural tissue in the two hemispheres during simple and complex finger movements performed either with the right hand or with the left hand. Simple movements consisted in contraction/extension of the index finger and complex movements in successive finger-thumb opposition from little finger to index finger. A general predominance of left-hemisphere activation relative to right hemisphere activation was found. Increasing the complexity of the motor activity resulted in an enlargement of the volume of consistently activated areas and greater involvement of ipsilateral areas, especially in the left hemisphere. Movements of the dominant hand elicited large contralateral activation (larger than movements of the non-dominant hand) and relatively smaller ipsilateral activation. Movements of the non-dominant hand resulted in a more balanced pattern of activation in the two hemispheres, due to relatively greater ipsilateral activation. This suggests that the dominant (right) hand is controlled mainly by the contralateral (left) hemisphere, whereas the non-dominant hand is controlled by both left and right hemispheres. This effect is especially apparent during execution of complex movements. The expansion of brain areas involved in motor control in the hemisphere contralateral to the dominant hand may provide neural substrate for higher efficiency and a greater motor skill repertoire of the preferred hand.
EN
T cell activation is a key event triggering an antigen specific immune response of the organism. The process is induced primarily by signal generated by direct interaction of T cell receptor (TCR) with antigen bound to major histocompatibile complex (MHC) on antigen presenting cell (APC). Although the signal is critical to excite immune response, however additional, costimulating signal is required. The major second signal is generated by interaction of CD28 molecule expressed on most T lymphocytes with its natural ligands CD80 and CD86 located on APCs. Signal excited by CD28 triggering involves multiple second messenger cascades, leading to activation of transcription factors and finally results in cell proliferation, cytokine production, and generation of effector function. The importance of CD28-delivered costimulatory signals was proven in experiments with CD28-deficient mice. T cells from these mice exhibit, impaired pattern of cytokine secretion, defects in T cell dependent antibody production. Certain forms of immunopathology might result from the aberrant regulation of CD28 expression.
EN
A multitude of heat shock transcription factors (HSFs) have been isolated and characterized from various plant species (17-23). Based on a phylogeny analysis of the DNA binding domains and organization of oligomerization domains, they have been assigned to class A and B of the plant HSF family (20,24 and this paper). None of the tested soybean or Arabidopsis HSF class B members were able to function as transcriptional activators and are, therefore, considered to be inert (26,59). Conversely, class A HSFs from tomato and Arabidopsis displayed an intrinsic transcriptional activation potential (26,50). There seems to be variation among plant class A HSFs regarding their transcriptional activation functions: some play a key role in activation of the heat shock response, while others act in an auxiliary capacity as HSF activity boosters (54). In contrast, the class B inert HSFs are able to trans-attenuate the transcriptional activity of activator HSFs (26). We postulated that heat shock regulation in plants may differ from metazoans by partitioning negative and positive functional domains onto separate HSF proteins (59). In plants two classes of HSFs exist: class A members which function as activators of HSP gene expression, and a novel class B (inert HSFs) which is largely specialized for repression, or attenuation, of the heat shock response.
EN
'Arousal' at a particular time has been defined as the energetic state at that moment, reflected in electrodermal activity and measured by skin conductance level. In contrast, task related 'activation' has been defined as the change in arousal from a resting baseline to the task situation. The present study, replicating some aspects of a previous investigation of these ideas in children, aimed to further explore whether the separation of 'arousal' and 'activation' was useful in describing state effects on the phasic Orienting Response (OR) and behavioral performance. A continuous performance task (CPT) was used with normal adults. It was found that the magnitude of the mean phasic OR to targets was dependent on arousal, but not on task-related activation. A performance measure (reaction time) improved with increasing activation, but not with arousal. These findings support our previous suggestions concerning the value of conceptualizing arousal and activation as separable aspects of the energetics of physiological and behavioral function.
EN
The force needed to press the key in a simple reaction time task was measured as a function of stimulus intensity for visual and auditory stimuli in the three experiments using a total 45 male and female human objects.Intensity ranged from 0.316 to 1995 cd/sq.m for visual stimuli and from ranged from 47 to 102 dB for auditory stimuli.We found, an in agreement with Angel's original study, that for auditory stimuli higher intensity is accompanied by a larger force.Suprisingly, in the case of visual stimuli the intensity does not influence the force.These findings are explained by the assumption that the changes of force reflect the changes of unspecific activation level evoked by immediate arousal.Thus, the different behaviour of force for these two modalities is in agreement with the common view that loud auditory stimuli are arousing while intense visual ones are not.
EN
Activation of caspases is the key event during apoptosis. Abnormalities of this phenomenon play an important role in the pathogenesis of several disorders and may have important clinical implications, including the development of novel therapeutic strategies. Currently, these problems are extensively investigated in several experimental and clinical studies.
EN
A plethora of heat shock transcription factors (HSFs) has been obtained from various plant species (33,45-48,50,51). The Arabidopsis genome sequencing project provided confirmation of the existence of at least twenty one HSFs which were classified into three major classes, A, B and C, and numerous subclasses (9). Members of HSF class A displayed differential transcriptional activities in tobacco protoplasts that varied from 15- to 50-fold above the control level. This diversity of activity levels may reflect HSF variations regarding their transcriptional activation functions- some of the members might be the major heat inducible HSFs (class A1 HSFs), while others act in an auxiliary capacity as HSF activity boosters (38). Two new class B HSFs showed no transcriptional activation potential; however, they differed significantly in their ability to bind to heat shock elements (HSEs). The efficiency in HSE binding was linked directly with the ability to suppress the activity of endogenous tobacco HSFs. The suppression of endogenous HSFs by class B members provides further evidence that class B HSFs are not transcriptional activators, but are able to trans-attenuate the transcriptional activity of bona fide activator HSFs (34,41). The transcriptional competency of class C HSFs has not been determined.
EN
Based on previous work indicating different neural substrates, two aspects of energetic state, 'arousal' and 'activation', have been conceptualized separately in our laboratory. 'Arousal' has been defined as the energetic state at any particular time, and task-related 'activation' as the task-related change in state from resting baseline to the task situation. Both are reflected in electrodermal activity and measured by skin conductance level. Our previous studies in this area have indicated that physiological responses to stimuli in a task are dependent on the arousal level at the time of stimulus presentation, rather than the task-related activation. In contrast, performance on the task is dependent on the task-related activation, rather than the current arousal level. That is, different aspects of the individual's state determine physiological and behavioral responses. Those studies had examined between-subjects differences in arousal and activation. The present study investigated the relevance of this separation in an across-subjects examination of fluctuations in arousal and activation, and their effects on physiological and behavioral responses, during a continuous performance task. It was found that the magnitude of the phasic orienting reflex to the targets during the task was dependent mainly on arousal, rather than task-related relative activation. Reaction time improved with increasing relative activation, but not with arousal. These findings support our earlier conclusions relating to the usefulness of arousal and activation as distinguishable features of the energetics of physiological and behavioral functions.
EN
Mast cells (MCs) are both central effectors and signaling cells in allergic reactions. Their key role in the immunopathology of asthma and other allergic diseases has been well documented. Molecular events leading to MC activation have not been yet fully established, however. Recent studies emphasize the key role of the protein tyrosine kinases Lyn and Fyn in MC signal transduction. The finding that Lyn kinase negatively regulates MC degranulation and that Fyn kinase enhances this effector response is of great importance. This creates new possibilities for therapeutic intervention in asthma and other allergic diseases. This review summarizes current knowledge on MC intracellular signaling and discusses the most recent strategies for the treatment of allergic diseases based on MC signaling pathway inhibition.
EN
The first line of treatment for many human autoimmune diseases involves the use of anti-inflammatory or immunosuppressive drugs such as prednisone or other steroids that not only suppress the underlying autoimmune disease, but lead to global suppression of the immune system. The sequelae of this approach include increased risk of infection, carcinogenesis, and osteoporosis. Moreover, such broad spectrum immunosuppression tends to have transient therapeutic benefit, as in many cases the disease becomes refractory to these drugs. There is a clear need for more specific means to restore immune tolerance to the specific autoantigens implicated in disease pathology. This review provides an overview of some of these newer, more specific therapeutic approaches to restoring immune tolerance to autoantigens, with an emphasis on those approaches that have been or will soon be tested in controlled clinical trials. Covered here are peptide- or protein-based therapeutics, oral tolerance, and cellular and gene therapy approaches to restoring antigen-specific immune tolerance.
EN
One of the most important factors that affect the developmental competences of mammalian somatic cell nuclear transfer (SCNT) embryos is artificial activation of reconstructed oocytes (clonal cybrids). However, calcium signal transduction in a cytosol of such oocytes that has been initiated incorrectly by physical or chemical activating factors (electric pulses or specific ionophore antibiotics) can stimulate not only the development of cloned embryos. It can also induce apoptotic cell death following considerable elevation in intracellular calcium concentration and thereby excitotoxicity of Ca2+ ions. Therefore, the basic objective of this paper is to present the current knowledge on the mechanisms regulating biochemical and biophysical proapoptotic changes within SCNT embryos via the process of excitotoxic calcium signal transmission resulting from an improper artificial activation of clonal cybrid.
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