Differences In Response Sensitivity Research Articles

Swimming behaviour in two ecologically similar three-spined (Gasterosteus aculeatus L.) and nine-spined sticklebacks (Pungitius pungitius L.): a comparative approach for modelling the toxicity of metal mixtures.

Sticklebacks (Gasterosteiformes) are increasingly used in ecological and evolutionary research and have become well established as role model species for biologists. However, ecotoxicology studies concerning behavioural effects in sticklebacks regarding stress responses, mainly induced by chemical mixtures, have hardly been addressed. For this purpose, we investigated the swimming behaviour (including mortality rate based on 96-h LC50 values) of two ecologically similar three-spined (Gasterosteus aculeatus) and nine-spined sticklebacks (Pungitius pungitius) to short-term (up to 24 h) metal mixture (MIX) exposure. We evaluated the relevance and efficacy of behavioural responses of test species in the early toxicity assessment of chemical mixtures. Fish exposed to six (Zn, Pb, Cd, Cu, Ni, and Cr) metals in the mixture were either singled out by the Water Framework Directive as priority or as relevant substances in surface water, which was prepared according to the environmental quality standards (EQSs) of these metals set for inland waters in the European Union (EU) (Directive 2013/39/EU). The performed behavioural analysis showed the main effect on the interaction between time, species, and treatment variables. Although both species exposed to MIX revealed a decreasing tendency in swimming activity, these species' responsiveness to MIX was somewhat different. Substantial changes in the activity of G. aculeatus were established after a 3-h exposure to MIX solutions, which was 1.43-fold lower, while in the case of P. pungitius, 1.96-fold higher than established 96-h LC50 values for each species. This study demonstrated species-specific differences in response sensitivity to metal-based water pollution, indicating behavioural insensitivity of P. pungitius as model species for aquatic biomonitoring and environmental risk assessments.

Rapid Reaction, Slow Dissociation Aggregation, and Synergetic Multicolor Emission for Imaging the Restriction and Regulation of Biosynthesis of Cys and GSH.

Biosynthesis is a necessary process to maintain life. In recent years, research has fully shown that three kinds of biothiols (Cys, Hcy, GSH) mainly play the role in oxidative stress and maintaining cell homeostasis in cells, and that abnormal concentrations will lead to the occurrence of cardiovascular diseases, cancers, etc. Various fluorescent probes have shown unprecedented advantages in detecting their concentrations and studying their biological functions. As a matter of fact, these three kinds of biothiols are generated in the process of biosynthesis in vivo. It is of great significance to understand their biosynthetic pathways and elucidate their synthetic relationships. In this work, to α,β-unsaturated ketones conjugated ethylenediamine coumarin and pyrandione was introduced boron fluoride and, through its strong electron deficiency effect, afforded a molecule having near-infrared emission and regulated the rigidity of molecules. At the same time, the conjugated double bond is used to respond to molecular rigidity. The rapid response of the probe to biothiols and the slow dissociation aggregation of the probe itself through the response environment could monitor the absence of biothiols in cells. In addition, based on the difference in sensitivity of response of Cys and GSH to the probe, this work studied the interaction between biosynthetic pathways of Cys and GSH in cells through enzyme inhibition for the first time. The relationship of restriction and regulation of biosynthesis in vivo was revealed.

Application of a behavioural and biochemical endpoint in ecotoxicity testing with Exaiptasia pallida.

Exaiptasia pallida has been applied as a cnidarian model to assess the toxicity of various contaminants using endpoints related to growth, reproduction and mortality. However, increasingly accepted behavioural and biochemical endpoints are underrepresented in ecotoxicity testing with cnidarian species. The aim of this study was to assess the suitability of tentacle retraction and superoxide dismutase activity as behavioural and biochemical endpoints for ecotoxicity testing with E. pallida. A concentration-dependent, tentacle retraction response was found in sub-lethal toxicity testing for anemones exposed to 1–65 μg L−1 Cu and 2–630 μg L−1 Zn for 24 and 96 h. Semi-quantitative and quantitative approaches to tentacle retraction analysis showed a difference in response sensitivity, however, both methods resulted in similar 24- and 96-h EC50 values for Cu and Zn. Additionally, tentacle retraction analysis provided the benefit of identifying recovery in anemones previously exposed to 359 μg L−1 Zn following a 96-h recovery period. Conversely, no significant difference in superoxide dismutase activity was detected in anemones exposed to the Cu and Zn solutions compared with controls, after either 24- or 96-h exposures. These findings support the ease of application and sensitivity of tentacle retraction as an endpoint in ecotoxicity testing with E. pallida and recommend its suitability for use in acute, sub-lethal toxicity testing. Moreover, evidence of recovery in E. pallida following exposure suggests that recovery should be incorporated into future toxicity assessments.

Autistic traits modulate cortical responses to affective but not discriminative touch.

The sense of touch is primarily considered a discriminative and exteroceptive sense, facilitating the detection, manipulation and exploration of objects, via an array of low-threshold mechanoreceptors and fast conducting A-beta (Aβ) afferents. However, a class of unmyelinated, low-threshold mechanoreceptors identified in the hairy skin of mammals have been proposed to constitute a second, anatomically distinct system coding the affective qualities of touch. Unlike Aβs, which increase their firing rate linearly with the velocity of a stimulus moving across their receptive field, the response of these C-tactile afferents (CTs) is described by an inverted 'U' curve fit, responding optimally to a skin temperature stimulus moving at between 1 and 10cm/s. Given the distinct velocity tuning of these fast and slow touch fibres, here we used event-related potentials to compare the time course of neural responses to 1st (fast) and 2nd (slow) touch systems. We identified a higher amplitude P300 in response to fast, Aβ-targeted, versus slow CT-targeted, stroking touch. In contrast, we identified a previously described, C-fibre specific, ultra-late potential (ULP) associated with CT-targeted input. Of special note as regards the function of CTs is that the amplitude of the ULP was negatively correlated with self-reported levels of autistic traits, which is consistent with the hypothesized affective and social significance of this response. Taken together, these findings provide further support for distinct discriminative and affective touch systems and suggests the temporal resolution of EEG provides an as yet underutilized tool for exploring individual differences in response sensitivity to CT-targeted touch.

Relative effective potencies of dioxin-like compounds in rodent and human lung cell models

Toxicity of dioxin-like compounds (DLCs), such as polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls, is largely mediated via aryl hydrocarbon receptor (AhR) activation. AhR-mediated gene expression can be tissue-specific; however, the inducibility of AhR in the lungs, a major target of DLCs, remains poorly characterized. In this study, we developed relative effective potencies (REPs) for a series of DLCs in both rodent (MLE-12, RLE-6TN) and human (A549, BEAS-2B) lung and bronchial epithelial cell models, using expression of both canonical (CYP1A1, CYP1B1) and less well characterized (TIPARP, AHRR, ALDH3A1) AhR target genes. The use of rat, murine and human cell lines allowed us to determine both species-specific differences in sensitivity of responses to DLCs in lung cellular models and deviations from established WHO toxic equivalency factor values (TEF) values. Finally, expression of selected AhR target genes was determined in vivo, using lung tissues of female rats exposed to a single oral dose of DLCs and compared with the obtained in vitro data. All cell models were highly sensitive to DLCs, with murine MLE-12 cells being the most sensitive and human A549 cells being the least sensitive. Interestingly, we observed that four AhR target genes were more sensitive than CYP1A1 in lung cell models (CYP1B1, AHRR, TIPARP and/or ALDH3A1). We found some deviations, with strikingly low REPs for polychlorinated biphenyls PCBs 105, 167, 169 and 189 in rat RLE-6TN cells-derived REPs for a series of 20 DLCs evaluated in this study, as compared with WHO TEF values. For other DLCs, including PCBs 126, 118 and 156, REPs were generally in good accordance with WHO TEF values. This conclusion was supported by in vivo data obtained in rat lung tissue. However, we found that human lung REPs for 2,3,4,7,8-pentachlorodibenzofuran and PCB 126 were much lower than the respective rat lung REPs. Furthermore, PCBs 118 and 156 were almost inactive in these human cells. Our observations may have consequences for risk assessment. Given the differences observed between rat and human data sets, development of human-specific REP/TEFs, and the use of CYP1B1, AHRR, TIPARP and/or ALDH3A1 mRNA inducibility as sensitive endpoints, are recommended for assessment of relative effective potencies of DLCs.

An Observed Effect of p53 Status on the Bystander Response to Radiation-Induced Cellular Photon Emission.

In this study, we investigated the potential influence of p53 on ultraviolet (UV) signal generation and response of bystander cells to the UV signals generated by beta-irradiated cells. Five cell lines of various p53 status (HaCaT, mutated; SW48, wild-type; HT29, mutated; HCT116+/+, wild-type; HCT116-/-, null) were irradiated with beta particles from tritium. Signal generation (photon emission at 340 ± 5 nm) was quantified from irradiated cells using a photomultiplier tube. Bystander response (clonogenic survival) was assessed by placing reporter cell flasks directly superior to irradiated signal-emitting cells. All cell lines emitted significant quantities of UV after tritium exposure. The magnitudes of HaCaT and HT29 photon emission at 340 nm were similar to each other while they were significantly different from the stronger signals emitted from SW48, HCT116+/+ and HCT116-/- cells. In regard to the bystander responses, HaCaT, HCT116+/+ and SW48 cells demonstrated significant reductions in survival as a result of exposure to emission signals. HCT116-/- and HT29 cells did not exhibit any changes in survival and thus were considered to be lacking the mechanisms or functions required to elicit a response. The survival response was found not to correlate with the observed signal strength for all experimental permutations; this may be attributed to varying emission spectra from cell line to cell line or differences in response sensitivity. Overall, these results suggest that the UV-mediated bystander response is influenced by the p53 status of the cell line. Wild-type p53 cells (HCT116+/+ and SW48) demonstrated significant responses to UV signals whereas the p53-null cell line (HCT116-/-) lacked any response. The two mutated p53 cell lines exhibited contrasting responses, which may be explained by unique modulation of functions by different point mutations. The reduced response (cell death) exhibited by p53-mutated cells compared to p53 wild-type cells suggests a possible role of the assessed p53 mutations in radiation-induced cancer susceptibility and reduced efficacy of radiation-directed therapy.

Comparative study of early interactions in mother–child dyads and care centre staff–child within the context of Chilean crèches

Bowlby developed the concept of 'caregiver' to refer to significant adults with whom young children interact daily. Not only parents are considered significant caregivers but also the care centre staff where the child attends regularly. Within caregiver-infant interactions, sensitive response on the part of the adult is a key concept in the assessment of the quality of the relationship, as it integrates the experiences and emotions that will influence the attainment of a secure attachment and a favourable emotional, social and cognitive development in the child. This study is a comparative analysis between the dyadic interactions between a child and its principal caregivers in the home and in the crèche; it is based on a group of 185 children between 8 and 24 months old, who attend a crèche regularly. The Care-Index instrument was used to assess interaction between children and adults, analysing sensitive response in the adults and cooperativeness in the children. The sensitive response of adults to children was complementary; mothers and primary caregivers showed greater sensitivity in the affective aspects of the interaction, while the care centre staff showed greater sensitivity in the cognitive aspects. The fact that caregivers show significant differences in response sensitivity is consistent with existing studies, as are corresponding significant differences in the children's cooperativeness, which demonstrates that a child could benefit from interacting with adults whose different skills could strengthen diverse aspects of health child development. The presence of children in the crèche can be a positive experience in that it favours quality exchanges with the child, developing cognitive aspects of the interaction which are cultivated to a lesser degree by mothers or primary caregivers who principally develop affective aspects.

Comparative roles of acetylcholine and noradrenaline in controlling the spontaneous activity of cortical neurons

The effects of acetylcholine and noradrenaline on the spike activity of neurons recorded in guinea pig parietal cortex slices were studied. Iontophoretic application of these two neurotransmitters to cortical neurons induced similar responses consisting of slowly developing and prolonged increases in spike activity. Differences in the temperature sensitivity of responses to acetylcholine and noradrenaline were identified. When the incubation medium temperature was increased from 32-34 degrees C to 35-36 degrees C, the effects of acetylcholine on neuron spike activity increased sharply, with the result that neurons which showed no spontaneous activity at 32-34 degrees C became sensitive to acetylcholine. The temperature-dependent increases in the extent of responses to acetylcholine were accompanied by stable increases in the level of spontaneous activity. Responses to application of noradrenaline showed no significant change when the temperature increased from 32-34 degrees C to 35-36 degrees C. Since neuron responses to the iontophoretic application of glutamate, the major excitatory neurotransmitter in the cortex, remained constant over this range of temperatures, the data obtained here lead to the conclusion that acetylcholine is the main regulator of the level of spontaneous activity of cortical neurons.

Comparative study on the in vitro/in vivo estrogenic potencies of 17β-estradiol, estrone, 17α-ethynylestradiol and nonylphenol

The estrogenic activity of compounds was evaluated in a comparative approach both with in vitro and in vivo assays. By comparing simultaneously obtained experimental data, we evaluated the differences in response sensitivity (by EC10) and concentration–response relationships (including EC50) in order to get an idea about the predictive value of in vitro assays for in vivo estrogenic potencies or effects in fish. Two human estrogen receptor-based assays, the MVLN-assay (transformed MCF-7 human breast cancer cell line) and the yeast estrogen screen (YES-screen) were used for the in vitro evaluation of the estrogenic potencies. An in vivo model with the female zebrafish ( Danio rerio) with plasma vitellogenin (VTG) as a biomarker for exposure and the ovarian somatic index (OSI) as an effect endpoint was used for the in vivo work. Compounds tested were 17β-estradiol (E2), estrone (E1), 17α-ethynylestradiol (EE2) and the alkylphenolic compound nonylphenol (NP). All compounds were found to be estrogenic in both in vitro assays and were able to induce VTG and to reduce the ovarian somatic index in female zebrafish. The MVLN-assay appeared up to 15 times more sensitive than the YES-screen. Concentration–response relationships, determined by EC10 and EC50 (concentration of test compound causing 10% or 50% effect compared to control) for VTG and OSI were of the same order of magnitude, indicating that VTG induction as an exposure biomarker can be predictive for effects on ovaries in females. We further demonstrated that for E1 and NP, the in vitro observed estrogenic potencies, based on EC50 values, were of the same order of magnitude as the in vivo estrogenic potencies. For EE2, a difference between in vitro and in vivo relative estrogenic potency was observed, being about 25 times more potent in vivo than could be expected based on the in vitro results. These experimental results showed the suitability of in vitro assays for screening purposes with qualitative assessment of estrogenicity, but they meanwhile point to the need of in vivo tests for an accurate hazard assessment for wildlife.

Design and Synthesis of Bipyridyl-Containing Conjugated Polymers: Effects of Polymer Rigidity on Metal Ion Sensing

Three conjugated polymers comprised of 9,9-dioctylfluorene and 2,2‘-bipyridine, which are alternatively linked by the C−C single bond (P1), vinylene bond (P2), or ethynylene bond (P3), have been synthesized via the Suzuki reaction, the Wittig−Horner reaction, and the Heck reaction, respectively. The optical, electrochemical, and other physical properties of the polymers are dependent on the linkers. The polymer linked by the C−C single bond exhibits a much larger Stokes shift compared with the other two polymers, indicative of higher extended and rigid backbone conformations in the polymers linked by the vinylene and ethynylene bonds. All the three polymers are sensitive to the existence of a variety of transition metal ions due to the chelation between the 2,2‘-bipyridyl moieties and the metal ions. For the metal ions which have moderate and weak coordination ability with the 2,2‘-bipyridyl moieties, an obvious difference in response sensitivity is observed among the three polymers: P1 has the highest s...

A test of catastrophe models of anxiety and sports performance against multidimensional anxiety theory models using the method of dynamic differences

Guastello's method of dynamic differences was used to fit catastrophe and multidimensional anxiety theory based behavior surfaces to data obtained from eight experienced golfers. The subjects were first taught to self-report their cognitive anxiety, somatic anxiety, and self-confidence levels as a single integer on a scale from 1 (low) to 27 (high). These single integer scales were then used to monitor levels of cognitive anxiety, somatic anxiety, and self-confidence, together with physiological arousal (operationalized as heart rate), prior to each putt during a Stapleford golf competition. All data was standardized within subjects in order to control for individual differences in response sensitivity and putting ability. Preliminary examination of the results suggested that the catastrophe models were superior to the multidimensional anxiety theory models, and that the inclusion of self-confidence significantly improved the goodness of fit of both models. However, further tests of other control models suggested that the apparent superiority of the catstrophe models was probably due to the inclusion of a temporal factor in Guastello's method of dynamic differences. It was concluded that the results do not offer any clear evidence for the superiority of either catastrophe or multidimensional anxiety theory based models of anxiety and performance. They do suggest that self-confidence is an important factor in performance which is at least partially independent of cognitive anxiety. They also suggest that future research might benefit considering performance as an ongoing temporal process rather than a discrete event.

Induction of chromosome aberrations by fusarium T-2 toxin in cultured human peripheral blood lymphocytes and Chinese hamster fibroblasts.

T-2 toxin is an important representative of trichothecenes produced by various species of imperfect fungi, mainly Fusarium genus. It is a naturally occurring toxin that can cause severe diseases in human and animals. No definite data demonstrating the carcinogenic potential of T-2 toxin had been reported up to now. We demonstrated that T-2 toxin reproducibly induced chromosomal structural aberrations both in cultured human peripheral blood lymphocytes as well as in V79 Chinese hamster fibroblasts. The mean percentage of cells with aberration of human lymphocytes from normal individuals induced by T-2 toxin is 49-fold (9.8%) of the mean percentage of corresponding control cultures without T-2 toxin (0.2%). T-2 toxin induced chromosome type (76%) as well as chromatid type (24%) of aberrations; among them, acentric fragment (46%) was the most common type, and chromatid gap, deletion, and chromosome gap were the next most common. T-2 toxin can induce aberrations in cells at different phases of the cell cycle. There are definite dose-effect relationships within a certain range of dosage of T-2 toxin in experiments with both human peripheral blood lymphocytes and V79 cells. T-2 toxin exhibited three types of effects on cells, namely, mitogenic at lowest concentration, clastogenic (chromosome aberration) at median concentration, and cytotoxic at higher concentration. The dose-effect curves of these three effects are partly overlapping. There is some interindividual difference in sensitivity of response for the clastogenic effect of T-2 toxin, but no resistant individual was observed. Sex or age effect was not observed. The above results suggest that T-2 toxin has carcinogenic potentials. The dosage of aflatoxin that can induce chromosomal aberration of human peripheral blood lymphocytes is thousands-fold of the dosage of T-2 toxin as shown in this report. T-2 toxin might have more hazardous potentials than had been previously considered. The carcinogenic potential of T-2 toxin and related trichothecenes and their possible roles in carcinogenesis of upper gastrointestinal (G.I.) tract cancers need to be further investigated.

Responses of vestibulospinal neurons to neck and macular vestibular inputs in the presence or absence of the paleocerebellum.

1. The role of the paleocerebellum in determining the responses of lateral vestibular nucleus (LVN) neurons either to independent or combined stimulation of macular vestibular and neck receptors has been investigated in decerebrate cats. Sinusoidal rotation around the longitudinal axis at 0.026 Hz, 5-10 degrees, represented the constant input parameters. Among the tested neurons, 100 and 131 units were recorded in animals with intact cerebellum and following partial cerebellectomy, respectively. The units were classified according to their anatomical location in either the rostroventral (cLVN) or dorsocaudal (ILVN) part of the LVN; units also were activated antidromically from the spinal cord. 2. The majority of units responded to stimulation of macular receptors both in preparations with intact cerebellum (75.0%) or with partial cerebellectomy (71.8%), the response being primarily in phase with the direction of animal orientation. The proportion of responding units and their response sensitivity were greater in the cLVN than ILVN in each preparation; no significant differences in mean firing rate and response sensitivity were observed between the two preparations for each subdivision of the LVN. In animals with cerebellum intact, the majority of cLVN and ILVN units were excited during side-down tilt; following partial cerebellectomy, this predominant response pattern still was present in cLVN but was reversed in ILVN. 3. About one-half of the units responded to sinusoidal stimulation of neck receptors in both preparations, the response being mainly in phase with the direction of neck orientation. In the intact cerebellum preparations, the proportion of cLVN units responding to neck rotation was greater than that of ILVN units, but no difference in response sensitivity was observed between these units. Following partial cerebellectomy, the proportion of cLVN units responsive to the neck input was reduced but that of ILVN units was not; however, the average response sensitivity was halved for both cLVN and ILVN units. In preparations with cerebellum intact, most of the cLVN units were excited during side-down neck rotation, whereas ILVN units were excited mainly by rotation in the opposite sense; following partial cerebellectomy, the majority of units were excited during side-up neck rotation, not only in ILVN but also in cLVN. 4. Units receiving a convergent input from both receptors were more numerous in cLVN (72.7%) than ILVN (41.8%) in preparations with intact cerebellum; following partial cerebellectomy, this disproportion of responsive units in the two divisions (45.3% and 44.9%, respectively) disappeared, due to a reduced number of cLVN units responding to the neck input. In both preparations, the macular input had a relatively greater influence on the cLVN whereas the neck input was more effective on the ILVN. 5...

Adreno-cortical and medullary responses to adenosine 3'.5'-monophosphate.

By means of direct arterial perfusion of the isolated intact dog adrenal glands it has been found that adenosine 3′,5′-monophosphate stimulates the continuous secretion of hydrocortisone. During the period of administration of the nuclcotide, the character and magnitude of steroid secretion was comparable to that seen during perfusion of ACTH. Steroidogenesis by rat and guinea pig adrenal slices incubated with 3′,5′-monophosphate was alsostudied, and a species difference in sensitivity of response has been demonstrated. Cathechol amine secretion, studied in the dog adrenal preparation, was unaffected by perfusion of either ACTH or the nucleotide.