Antistress cross-effects of extracellular metabolites of bacteria, archaea, and yeasts: A review

This paper reviews examples of specific and global responses of microorganisms and the characteristics of stress responses involving extracellular signaling metabolites. Information regarding the protective and reactivating effects produced by active exometabolites of representatives of domains of bacteria, archaea, and eukaryotes is summarized, and interdomain cross-responses to stressors are demonstrated.     

Phosphatases join kinases in DNA-damage response pathways

An inappropriate imbalance of kinase and phosphatase activities could be deleterious to cellular processes such as proliferation. Cellular responses to DNA damage use signal-transduction pathways involving phosphorylation events, and such modifications must be reversible to make these responses transient, rather than permanent, events. Three recent articles describe roles for two phosphatases in signaling pathways that are activated after DNA damage.     

Protein kinase C, calcium and phospholipid degradation.

In most cells, calcium signals are transient, while the resulting physiological responses often persist longer. The sustained activation of protein kinase C has been postulated to be essential for maintaining such cellular responses. It is becoming clear that an elaborate network involving protein kinase C, calcium and degradation of membrane phospholipids may generate several molecules that are necessary for sustaining the activation of protein kinase C itself. Multiple members of the protein kinase C family show distinct responses to calcium and the phospholipid degradation products, suggesting their unique functions in cell signalling.     

Long latency transient evoked potentials to rapid random stimulation: responses to single and multiple concurrent stimuli

In EP testing, regular (periodic) stimulation at increasing rates produces progressive fusion of responses into steady-state wave forms. When stimuli are presented randomly in time this fusion does not occur. Medium and long latency transient EPs can be recorded to stimulation at interstimulus intervals which are much shorter than the EP wave form latencies. Individual transient EPs can be obtained to multiple independent stimuli presented concurrently when the stimuli are presented randomly to one another. The ability to obtain responses to rapid stimulation and to multiple independent stimuli provides opportunities for increased efficiency and complexity of testing, particularly involving long latency responses.     

Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC-mediated suppression of adaptive immune responses. Recently, we demonstrated that triiodothyronine (T3) has potent immunostimulatory effects on bone marrow-derived mouse DCs through a mechanism involving T3 binding to cytosolic thyroid hormone receptor (TR) β1, rapid and sustained Akt activation and IL-12 production. Here we explored the impact of GCs on T3-mediated DC maturation and function and the intracellular events underlying these effects. Dexamethasone (Dex), a synthetic GC, potently inhibited T3-induced stimulation of DCs by preventing the augmented expression of maturation markers and the enhanced IL-12 secretion through mechanisms involving the GC receptor. These effects were accompanied by increased IL-10 levels following exposure of T3-conditioned DCs to Dex. Accordingly, Dex inhibited the immunostimulatory capacity of T3-matured DCs on naive T-cell proliferation and IFN-γ production while increased IL-10 synthesis by allogeneic T cell cultures. A mechanistic analysis revealed the ability of Dex to dampen T3 responses through modulation of Akt phosphorylation and cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). In addition, Dex decreased TRβ1 expression in both immature and T3-maturated DCs through mechanisms involving the GC receptor. Thus GCs, which are increased during the resolution of inflammatory responses, counteract the immunostimulatory effects of T3 on DCs and their ability to polarize adaptive immune responses toward a T helper (Th)-1-type through mechanisms involving, at least in part, NF-κB- and TRβ1-dependent pathways. Our data provide an alternative mechanism for the anti-inflammatory effects of GCs with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits.     

Trans-signaling by cytokine and growth factor receptors

Although ligand-induced dimerization or oligomerization of receptors is a well established mechanism of growth factor signaling, increasing evidence indicates that biological responses are often mediated by receptor trans-signaling mechanisms involving two or more receptor systems. These include G protein-coupled receptors, cytokine, growth factor and trophic factor receptors. Greater responsiveness and inhibitory signaling responses are provided when different signaling pathways merge through receptor trans-signaling.     

Protein Kinases in Plants in the Transduction of Abiotic and Biotic Signals

The effects of extrinsic and intrinsic factors upon signaling pathways involving protein kinases are reviewed with particular reference to monomeric GTP-binding proteins and MAP kinases. The possible roles of feedback control and interactions between cascades in plant responses are stressed.     

Testing for Independence of Binary Responses

In the context of experiments involving visual inspection of random dot patterns the problem of testing the null hypothesis of independence of binary responses is considered. A flexible model for dependence between binary responses is proposed. Two tests, optimal under different versions of the model, are derived. These two tests turn out to involve the same computations as the Wilcoxon two sample test and the runs test respectively.     

Dendritic cell biology during malaria

Malaria is an infectious disease that causes serious morbidity and mortality worldwide. The disease is associated with a variety of clinical syndromes ranging from asymptomatic to lethal infections involving anaemia, organ failure, pulmonary and cerebral disease. The molecular and cellular factors responsible for the differences in disease severity are poorly understood but parasite-specific immune responses are thought to play a critical role in pathogenesis. Dendritic cells have an essential role in linking innate and adaptive immune responses and here we review their role in the context of malaria.     

Mixed effects models with bivariate and univariate association parameters for longitudinal bivariate binary response data

When two binary responses are measured for each study subject across time, it may be of interest to model how the bivariate associations and marginal univariate risks involving the two responses change across time. To achieve such a goal, marginal models with bivariate log odds ratio and univariate logit components are extended to include random effects for all components. Specifically, separate normal random effects are specified on the log odds ratio scale for bivariate responses and on the logit scale for univariate responses. Assuming conditional independence given the random effects facilitates the modeling of bivariate associations across time with missing at random incomplete data. We fit the model to a dataset for which such structures are feasible: a longitudinal randomized trial of a cardiovascular educational program where the responses of interest are change in hypertension and hypercholestemia status. The proposed model is compared to a naive bivariate model that assumes independence between time points and univariate mixed effects logit models.     

Auxin as compère in plant hormone crosstalk

The architecture of many hormone perceptions and signalling pathways has been recently well established, together with an awareness that plant hormone responses are the product of networks of interactions involving multiple hormones. As growth is quantitative, so are hormone responses, which underlie a systems approach to development and response. Auxin is arguably one of the best characterised hormones in plant development, and despite many excellent reviews on auxin perception, polar transport, and signal transduction, too little attention has been given to auxin crosstalk. This review, therefore, gives a précis of recent developments in hormone crosstalk involving auxin. For decades, the literature has described the involvement of multiple hormones in particular processes, although the mechanistic bases underlying points of crosstalk have been harder to pinpoint. Crosstalk falls into different categories, such as direct, indirect, or co-regulation. One conclusion for auxin crosstalk is that crosstalk operates extensively via the metabolism of other hormones, however, microarray approaches are increasingly identifying co-regulated genes and nodes of crosstalk at shared signalling components. Auxin crosstalk is often local, and is spatially and temporally regulated to provide adaptive value to environmental conditions and fine-tuning of responses.     

T cell recognition of nonpolymorphic determinants on H-2 class I molecules

Recognition of polymorphic determinants on class I or class II MHC Ag is required for T lymphocyte responses. Using cell-size artificial membranes (pseudocytes) bearing H-2 class I Ag it is demonstrated that T cells can, in addition, recognize nonpolymorphic determinants on class I proteins. Pseudocytes bearing class I alloantigen stimulate in vitro generation of secondary allogeneic CTL responses. At a suboptimal alloantigen surface density, incorporation of class I molecules identical to those of the responder cells (self-H-2) or from third-party cells resulted in dramatically enhanced responses, whereas incorporation of class II proteins had no effect. The receptor that mediates recognition of conserved class I determinants has not been identified, but results of antibody blocking studies are consistent with the Lyt-2/3 complex of CTL having this role. Thus, class I proteins on Ag-bearing cells can have two distinct roles in T cell activation, one involving recognition of polymorphic determinants by the Ag-specific receptor and the other involving recognition of conserved determinants.     

A haplotype-specific Resistance gene regulated by BONZAI1 mediates temperature-dependent growth control in Arabidopsis

Plant growth homeostasis and defense responses are regulated by BONZAI1 (BON1), an evolutionarily conserved gene. Here, we show that growth regulation by BON1 is mediated through defense responses. BON1 is a negative regulator of a haplotype-specific Resistance (R) gene SNC1. The bon1-1 loss-of-function mutation activates SNC1, leading to constitutive defense responses and, consequently, reduced cell growth. In addition, a feedback amplification of the SNC1 gene involving salicylic acid is subject to temperature control, accounting for the regulation of growth and defense by temperature in bon1-1 and many other mutants. Thus, plant growth homeostasis involves the regulation of an R gene by BON1 and the intricate interplay between defense responses and temperature responses.     

Protein polymorphism and evolution in the genus Tetrahymena.

Immunoblotting tests involving cytoskeletal protein arrays and fluorescence microscopical examinations of whole cells using monoclonal antibody 424A8 gave substantially different results in three evolutionary subgroups within the genus Tetrahymena. These responses are described and some implications of the evolutionary divergence indicated in this ciliated protozoan are discussed.     

Inhibitory effects of tetramethyl and tetraethyl derivatives of pyrazine on dog saphenous vein.

The effects of two structurally similar pyrazine derivatives, tetramethylpyrazine (TMP) and tetraethylpyrazine (TEP) on the contractile responses of dog saphenous vein to KCl (via membrane depolarization), phenylephrine (PHE, alpha 1-adrenergic agonist), and B-HT 920 (alpha 2-adrenergic agonist) were investigated. The relaxant or inhibitory effect of TMP and TEP was most potent on KCl-induced responses and least potent on PHE-induced responses. Their effect on KCl-induced responses was more prominent at 30 mM KCl than at 100 mM KCl. In Ca(2+)-free medium, PHE and B-HT 920 elicited transient responses, which were also markedly and reversibly inhibited by TMP and TEP. Similar results were also obtained when prostaglandin F2 alpha was used as an agonist. In all four types of contractile responses involving different receptors, the inhibitory effect of TEP was consistently more potent than that of TMP. We conclude that both TMP and TEP behave as a nonselective smooth muscle relaxant having similar and multiple actions including their general interference with the processes involving both Ca2+ entry and intracellular Ca2+ release.     

Replacement interaction diagrams in interspecific competition experiments

Replacement interaction diagrams offer a new approach in displaying results of interspecific competition experiments. They allow visual assessment of both actual and relative responses of two species in a replacement series to treatments arranged in a factorial array. Yield data are plotted on a semi-logarithmic scale along the vertical axis. Treatments are arranged on the horizontal axis. The degree of interspecific interference or competition in mixed populations is best assessed by comparing the species response in a mixture with that in the monoculture. In competition experiments involving a number of treatment variables, replacement interaction diagrams highlight trends in treatment responses and allow some comparisions of responses between plant frequences.     

Effect of paraventricular nucleus lesions on cardiovascular responses elicited by stimulation of the subfornical organ in the rat

It has recently been reported that stimulation of the region of the subfornical organ (SFO) elicits an increase in arterial pressure. However, the mechanisms and forebrain neural circuitry that are involved in this cardiovascular response have not been elucidated. The present study was done in urethane-anaesthetized rats to determine whether selective activation of SFO neurons elicit cardiovascular responses and whether these responses were mediated by a pathway involving the paraventricular nucleus of the hypothalamus (PVH). Stimulation sites which required the lowest threshold current (30 microA) to elicit a pressor response and at which the largest rise in mean arterial pressure (MAP; 22 +/- 2 mmHg) was elicited at a constant current intensity (150 microA) were histologically localized in the region of the SFO. Short (mean peak latency; 4 +/- 2 s) and long (mean peak latency; 61 +/- 8 s) latency increases in MAP were observed during and after electrical stimulation of the SFO, respectively. Cardiac slowing accompanied the short latency pressor response and cardioacceleration was observed in most (57%) of the cases to accompany the late pressor response. Microinjection of L-glutamate into the SFO consistently elicited cardiovascular responses qualitatively similar to those observed during electrical stimulation. Ganglionic blockade abolished the short latency increase in MAP and the accompanying bradycardia. However, the long latency pressor and cardioacceleratory responses were not altered by ganglionic blockade and adrenalectomy. Selective bilateral electrolytic or kainic acid lesions of the region of the PVH significantly attenuated the cardiovascular responses elicited by stimulation of the SFO. These data suggest that activation of neurons in the SFO elicit cardiovascular responses partially mediated by sympathetic outflow through a neural pathway involving the PVH.