Genetic regulation of the antibody response to H-2Db alloantigens in mice

The cytotoxic antibody response to the H-2D^b alloantigen has been investigated in ten strains of the C57BL/10 background. Three types of responses could be distinguished: no detectable response, an IgM response, and an IgG response. The IgG response is influenced by the D and probably the I-A region of the H-2 complex, whereas the IgM response is dependent on the allele for the E chain. The hypothesis is proposed that regulatory T cells, which recognize the antigen in context of self MHC molecules, determine the outcome of an anti-H-2D^b immunization in which the I-E molecule restricts the IgM response and the I-A molecule restricts the IgG response; the D molecule is probably responsible for activation of suppressor T cells which suppress only the IgG response.     

Scototaxis and target perception in the camel tickHyalomma dromedarii

The camel tick,Hyalomma dromedarii, exhibited positive scototaxis in an arena, e.g. it oriented towards a black or grey target in front of a white background. The degree of the scototactic response varied with the size and the elevation of the target, with its luminance contrast, with its shape and with the speed by which the target was moved: (1) the response to stationary and moving targets increased with increasing target size; (2) presentation of the targets at an elevation of 11^o–15^o induced the highest response; (3) the response decreased with decreasing luminance contrast of the target; (4) targets with the shape of a disk, a triangle standing on a vertex, a vertical bar or a silhouette of a dromedary caused high responses; a low response was observed when the target was a horizontal bar and there was no response to a striped pattern; (5) the smaller the size of a disk, the faster it had to be moved to elicit an optimum response.The smallest disk which elicited a significant response appeared under a visual angle of 4.8^o for a thick at the starting point. The smallest dromedary-shaped silhouette which elicited a significant response corresponded to the silhouette of a real dromedary at a distance of 18 m.     

Metabolic Respiration Induces AMPK- and Ire1p-Dependent Activation of the p38-Type HOG MAPK Pathway

Evolutionarily conserved mitogen activated protein kinase (MAPK) pathways regulate the response to stress as well as cell differentiation. In Saccharomyces cerevisiae, growth in non-preferred carbon sources (like galactose) induces differentiation to the filamentous cell type through an extracellular-signal regulated kinase (ERK)-type MAPK pathway. The filamentous growth MAPK pathway shares components with a p38-type High Osmolarity Glycerol response (HOG) pathway, which regulates the response to changes in osmolarity. To determine the extent of functional overlap between the MAPK pathways, comparative RNA sequencing was performed, which uncovered an unexpected role for the HOG pathway in regulating the response to growth in galactose. The HOG pathway was induced during growth in galactose, which required the nutrient regulatory AMP-dependent protein kinase (AMPK) Snf1p, an intact respiratory chain, and a functional tricarboxylic acid (TCA) cycle. The unfolded protein response (UPR) kinase Ire1p was also required for HOG pathway activation in this context. Thus, the filamentous growth and HOG pathways are both active during growth in galactose. The two pathways redundantly promoted growth in galactose, but paradoxically, they also inhibited each other''s activities. Such cross-modulation was critical to optimize the differentiation response. The human fungal pathogen Candida albicans showed a similar regulatory circuit. Thus, an evolutionarily conserved regulatory axis links metabolic respiration and AMPK to Ire1p, which regulates a differentiation response involving the modulated activity of ERK and p38 MAPK pathways.     

Infant anticipatory stress

In humans, anticipatory stress involves activation of the limbic–hypothalamic–pituitary–adrenal axis, which releases stress hormones such as cortisol in response to an impending stressor. Conditioning of the stress response to anticipate and prepare for future challenges is a hallmark of adaptation. It is unknown whether human infants in the first year of life have developed the neural circuitry to support the anticipation of stressful events in an attachment context. Here, we show that human infants at six months of age produce an anticipatory stress response, as indicated by the release of stress hormones, when re-exposed after 24 h to a context in which they demonstrated a stress response to a disruption in the parent–infant relationship. Although infant stress response (cortisol elevation) was greater to the stressful event (parent unresponsiveness) than to the second exposure to the stress context (room, chair, presence of parent and experimenter, etc.), it was greater in the stress group than in the control group on both days. Results suggest that human infants have the capacity to produce an anticipatory stress response that is based on expectations about how their parents will treat them in a specific context.     

The adjuvant activity of synthetic N-acetylmuramyl-dipeptide: evidence of initial target cells for the adjuvant activity.

MurNAc-l-Ala-d-isoGln (N-acetylmuramyl-l-alanyl-d-isoglutamine, MDP), a synthetic compound, acts as an adjuvant on the humoral immune response and on the T cell-mediated immune response. In this report, we attempted to directly demonstrate the initial target cells of MDP for its adjuvant activity in vitro by using cell separation procedures.It was demonstrated that MDP enhanced the immune response following direct interaction with antigen-stimulated T and B lymphocytes, but nonstimulated lymphocytes, shortly after triggering by antigen, and that there was no macrophage requirement for MDP to elicite the adjuvant action in the primary anti-SRBC PFC response in vitro. It has also been demonstrated that the adjuvant activity of MDP is due to an enhancing effect which is different from the possible mitogenic activity to spleen cells and MDP replaces neither a function of macrophages, which is substituted by 2-mercaptoethanol nor a helper function of T cells.     

Abscisic Acid Elicits the Water-Stress Response in Root Hairs of Arabidopsis thaliana

Water stress has been shown to cause root hairs to become short and bulbous. Because abscisic acid (ABA) mediates a variety of water-stress responses, we investigated the response of Arabidopsis thaliana root hairs to ABA. When wild-type root hairs were treated with ABA, they exhibited the water-stress response. The Arabidopsis mutants abi1 and abi2, which are insensitive to ABA at the seedling stage, did not display the root hair response. These data suggest that ABA may mediate the response of root hairs to water stress. The drought response of root hairs resulting in an inhibition of tip growth will provide an easy screen to select mutations that are insensitive to ABA and/or involved in tip growth.     

Tropic Responses of Phycomyces Sporangiophores to Gravitational and Centrifugal Stimuli

A low-speed centrifuge was used to study the tropic responses of Phycomyces sporangiophores in darkness to the stimulus of combined gravitational and centrifugal forces. If this stimulus is constant the response is a relatively slow tropic reaction, which persists for up to 12 hours. The response is accelerated by increasing the magnitude of the gravitational-centrifugal force. A wholly different tropic response, the transient response, is elicited by an abrupt change in the gravitational-centrifugal stimulus. The transient response has a duration of only about 6 min. but is characterized by a high bending speed (about 5°/min.). An analysis of the distribution of the transient response along the growing zone shows that the active phase of the response has a distribution similar to that of the light sensitivity for the light-growth and phototropic responses. Experiments in which sporangiophores are centrifuged in an inert dense fluid indicate that the sensory mechanism of the transient response is closely related to the physical deformation of the growing zone caused by the action of the gravitational-centrifugal force on the sporangiophore as a whole. However, the response to a steady gravitational-centrifugal force is most likely not connected with this deformation, but is probably triggered by the shifting of regions or particles of differing density relative to one another inside the cell.     

Studies on transplantation immunity: III. The secondary response to dissociated allogeneic cells

The secondary response of CBA mice to dissociated (A X CBA)F₁ lymphoid cells has been studied with the aid of the ⁵¹Cr-labeling technique. The effect of a secondary dose is independent of the time interval between primary and secondary doses over a wide range, due presumably to the remarkably stable status induced by a single stimulus. No clear evidence of a true secondary has been found for the liver or spleen responses, which are largely mediated by antibody production. The lymph node response, which is largely cell mediated, does possess a true secondary. The dose response data for the lymph nodes show that the primary response has an initial impetus into tolerance, reversed by sensitisation; and that the secondary response is simpler in form than the primary. Only a restricted range of primary and secondary doses are capable of eliciting a secondary response. Various peculiarities of the secondary suggest that it may arise as an in vivo form of “mixed lymphocyte reaction.”     

No indications of an enhanced UV-light-induced unscheduled DNA synthesis in splenocytes of mice following a low-dose irradiation in vivo or in vitro

One of the open questions regarding the adaptive response to ionizing radiation is whether it can be induced in G₀ lymphocytes. In the majority of experiments in which an adaptive response in G₀ lymphocytes was observed, the adapting dose was applied in vivo. In order to investigate whether there is some in vivo component of adaptive response, mouse splenocytes of the C57BL/6 strain were irradiated with 0.1 Gy x-rays either in vivo or in vitro, and their UV-light-induced unscheduled DNA synthesis (UDS) levels were determined autoradiographically. An augmented UV-light-induced UDS following an adapting dose applied in vivo has previously been described by several authors in splenocytes of C57BL/6 mice, indicating that the adapting dose enhanced the DNA repair capacity of lymphocytes. In the present investigation, however, no evidence of an adaptive response could be seen regardless of whether the adapting dose was given in vivo or in vitro. Those results present a further indication for the fact that the adaptive response to ionizing radiation is not always inducible, even in lymphocytes of an inbred mouse strain in which its existence has been reported before.     

Different cell cycle modifications repress apoptosis at different steps independent of developmental signaling in Drosophila

Apoptotic cell death is important for the normal development of a variety of organisms. Apoptosis is also a response to DNA damage and an important barrier to oncogenesis. The apoptotic response to DNA damage is dampened in specific cell types during development. Developmental signaling pathways can repress apoptosis, and reduced cell proliferation also correlates with a lower apoptotic response. However, because developmental signaling regulates both cell proliferation and apoptosis, the relative contribution of cell division to the apoptotic response has been hard to discern in vivo. Here we use Drosophila oogenesis as an in vivo model system to determine the extent to which cell proliferation influences the apoptotic response to DNA damage. We find that different types of cell cycle modifications are sufficient to repress the apoptotic response to ionizing radiation independent of developmental signaling. The step(s) at which the apoptosis pathway was repressed depended on the type of cell cycle modification—either upstream or downstream of expression of the p53-regulated proapoptotic genes. Our findings have important implications for understanding the coordination of cell proliferation with the apoptotic response in development and disease, including cancer and the tissue-specific responses to radiation therapy.     

The auxin-resistant diageotropica mutant of tomato responds to gravity via an auxin-mediated pathway

 Hypocotyls of the diageotropica (dgt) mutant of tomato (Lycopersicon esculentum Mill.) do not elongate in response to exogenous auxin, but can respond to gravity. This appears paradoxical in light of the Cholodny-Went hypothesis, which states that shoot gravicurvature results from asymmetric stimulation of elongation by auxin. While light-grown dgt seedlings can achieve correct gravitropic reorientation, the response is slow compared to wild-type seedlings. The sensitivity of dgt seedlings to inhibition of gravicurvature by immersion in auxin or auxin-transport inhibitors is similar to that of wild-type plants, indicating that both an auxin gradient and auxin transport are required for the gravitropic response and that auxin uptake, efflux, and at least one auxin receptor are functional in dgt. Furthermore, dgt gravicurvature is the result of asymmetrically increased elongation as would be expected for an auxin-mediated response. Our results suggest differences between elongation in response to exogenous auxin (absent in dgt) and elongation in response to gravistimulation (present but attenuated in dgt) and confirm the presence of two phases during the gravitropic response, both of which are dependent on functional auxin transport. Received: 16 July 1999 / Accepted: 24 September 1999     

Light Response of a Giant Aplysia Neuron

Illumination of an Aplysia giant neuron evokes a membrane hyperpolarization which is associated with a membrane conductance increase of 15%. The light response is best elicited at 490 nM: the neuron also has an absorption peak at this wavelength. At the resting potential (-50 to -60 mV) illumination evokes an outward current in a voltage-clamped cell. This current reverses sign very close to E_K calculated from direct measurements of internal and external K⁺ activity. Increases in external K⁺ concentration shift the reversal potential of the light-evoked response by the same amount as the change in E_K. Decreases in external Na⁺ or Cl^- do not affect the response. Therefore, the response is attributed to an increase in K⁺ conductance. Pressure injection of Ca²⁺ into this neuron also hyperpolarizes the cell membrane. This effect is also due largely to an increase in K⁺ conductance. The light response after Ca²⁺ injection does not appear to be altered. Pressure injection of EGTA abolished or greatly reduced the light response. The effect was reversible. We suggest that light acts upon a single pigment in this neuron, releasing Ca²⁺ which in turn increases K⁺ conductance, thereby hyperpolarizing the neuronal membrane.     

Studies on Isolated Protoplasts and Vacuoles: II. THE ACTION OF GROWTH SUBSTANCES

The response of isolated protoplasts to indol-3-yl acetic acidwas investigated, and they were found to undergo a rapid water-uptakewith ultimate rupture of the plasmalemma and release of thelarge central vacuole. The use of a photomicrographic methodshowed that this response was optimal at 10^-5 M indol-3-yl aceticacid. No such response could be detected for isolated vacuoles.¹⁴C-labelled indol-3-yl acetic acid was used to obtain furtherinsight into the site of action of this growth substance. Evidenceis presented which suggests that the site of action of indol-3-ylacetic acid, for this response, is the plasmalemma, where itfacilitates an increased uptake of solutes which is followedby an osmotic water uptake.     

Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila

The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.     

Maturation of the angiotensin II cardiovascular response in the embryonic White Leghorn chicken (Gallus gallus)

Angiotensin II (Ang II) is an important regulator of cardiovascular function in adult vertebrates. Although its role in regulating the adult system has been extensively investigated, the cardiovascular response to Ang II in embryonic vertebrates is relatively unknown. We investigated the potential of Ang II as a regulator of cardiovascular function in embryonic chickens, which lack central nervous system control of cardiovascular function throughout the majority of incubation. The cardiovascular response to Ang II in embryonic chickens was investigated over the final 50% of their development. Ang II produced a dose-dependent increase in arterial pressure on each day of development studied, and the response increased in intensity as development progressed. The Ang II type-1 receptor nonspecific competitive peptide antagonist [Sar¹ ile⁸] Ang II blocked the cardiovascular response to subsequent injections of Ang II on day 21 only. The embryonic pressure response to Ang II (hypertension only) differed from that of adult chickens, in which initial hypotension is followed by hypertension. The constant level of gene expression for the Ang II receptor, in conjunction with an increasing pressure response to the peptide, suggests that two Ang II receptor subtypes are present during chicken development. Collectively, the data indicate that Ang II plays an important role in the cardiovascular development of chickens; however, its role in maintaining basal function requires further study.     

Immune response genes in chickens

The immunogenecity in chickens of the synthetic polypeptide TGAL is shown to be highly batch-dependent. Antibodies of at least two quite different specificities were formed: an MHC-linked anti-TG response, and a non-TG response (probably to poly-alanine) which is not linked to the MHC. Immunization with the random copolymer GT also gave rise to an anti-TG antibody response which showed a firm linkage to theB complex. It is concluded that GT may serve as a useful marker for an MHC-linked gene in chickens. Surprisingly, conjugation of GT to the immunogenic carrier MBSA did not convert low GT responder chickens to high responders. This finding raises the possibility that the low responder status may be the result of specific suppressor cells.     

Water Stress and Apical Morphogenesis in Barley

The formation of new primordia on the apical meristem of barley(Hordeum vulgare L.) was inhibited at levels of soil water potential(-1 bar and less) which had little or no effect on growth ofthe plant. Both leaf growth and morphogenesis of lateral spikeletson the developing ear proceeded at reduced rates at water-potentiallevels which completely suppressed primordium formation. Thissensitivity of the apex to stress was unaffected by floral initiationand was apparently not due to changes in water potential inthe apical tissues. Primordium formation was inhibited eventhough apical water potential was unchanged. Water stress suppressedthe response of the apical meristem to an increase in the photoperiodto which the plant was exposed. In some circumstances, however,the photoperiodic response was displayed after the stress wasrelieved. During an episode of moderate water stress it waspossible to observe an increase in the rate of primordium formationin response to an increase in light intensity.     

Biphasic Regulation in Ligand-Receptor Interactions

Abstract

A model is examined in which an excess of activator may inhibit the response in a ligand-receptor interaction. The equation accounts for biphasic responses in which an effector stimulates the response at low concentrations and then inhibits the response at higher concentrations, towards a limit that can be higher, identical or lower than the initial value. Reciprocal features could be observed according to the values of the involved parameters. A maximum 7 dimensions can be found in the space of the parameters of the equation which is of the simple form: v = (A + B + C). Sⁿ/(H + Sⁿ).     

On the role of persistent signaling and autocatalysis in the T-cell independent immune response

A kinetic model of the T-cell independent immune response is presented which includes two new mechanistic features. First, a persistent signaling mechanism is hypothesized which requires that proliferating cell receptor sites be continuously occupied in order for mitotic proliferation to occur. Second, an autocatalytic mechanism is introduced (coupled with the persistent signaling mechanism) which results in rapid termination of the B-cell response upon sufficient reduction of the antigen population.