Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia

Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient’s genotypes was analyzed with the patient’s response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The “G allele” of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.

     

Effect of Different Gibberellins on the Growth of the Hypocotyl

It has been stated earlier that hypocotyls of different plants show different growth response to added GA₃. It was suggested that this difference may be due to the requirement of some specific gibberellin. Hence hypocotyl growth response of three groups of plants has been studied with different gibberellins: group one showing no or insignificant growth response, group two showing 150–200 per cent growth response and group three showing 300–500 per cent growth response to added GA₃. Eight gibberellins were used, viz., GA₁, GA₂, GA₃, GA₄, GA₅, GA₇, GA₈ and GA₉, to test if this varying response is connected with the requirement of some specific gibberellin. In general, the results obtained do not favour this view. Iberis amara, a plant showing no response to added GA₃, Dianthus sp., a plant showing 150 to 200 per cent response and Lactuca satwa, Antirrhinum majus and Nicotiana tabacum, plants showing 300 to 500 per cent response, were promoted by all the gibberellins tested to a similar extent as by GA₃, with the exception of GA₈ which was inactive in most of the cases.     

Immune response to the Slp alloantigen in the mouse:H-2-linked qualitative and quantitative control

Immunization of inbred mouse strains lacking the Slp allotype results in the production of Slp antibodies in some strains but elicits no detectable response in other strains. Analysis of standard inbred and congenic resistant strains reveals that both the qualitative and quantitative ability to respond to the Slp allotype is associated with theH-2 haplotype of the recipient. Three different response phenotypes can be identified utilizing complement fixation and quantitative immunodiffusion tests. Strains which carry theH-2 ^q haplotype are high responders,H-2 ^k strains are intermediate in response, whileH-2 ^b andH-2 ^v strains produce no detectable antibody. The characteristic response patterns of high and intermediate responders were manifest by day 35 of immunization and continued as discrete response types after a second booster. Quantitative data in the immune response of the intra-H-2 recombinant B10.A(4R) suggest that the recombination event which established theH-2 ^h4 chromosome disturbs the proper function of the genetic determinant controlling response to Slp.     

Responses of the saucer scallop Amusium balloti to potential predators

A high natural mortality rate has been documented for the saucer scallop Amusium balloti, an Australian scallop found on sediment bottoms at 30–60 m deep, but little is known about the causes of mortality. We studied escape responses of A. balloti to five consumers common in the bycatch of the scallop fishery as a means of identifying potential predators. The scallop showed a negligible to weak response when touched with the sea star Pentaceraster regulus and the red portunid crab Portunus rubromarginatus. The response was similar to that observed when the scallop was touched with a plastic object. In contrast, A. balloti showed a consistent and vigorous swimming response to contact with the slipper lobster Thenus orientalis, the blue swimmer crab Portunus pelagicus and the coral crab Charybdis cruciata. This was not a generalized response to crustaceans, given the scallop's weak response to the red portunid crab. This is the first report of a scallop that has a strong swimming escape response to contact with decapod crustacean predators.     

Genetic and functional analyses of the primary in vitro CTL: Response of NZB lymphocytes toH-2-compatible cells

Spleen cells from NZB mice make an unexpected primary cytotoxic T lymphocyte (CTL) response to BALB/c cells in vitro. In this study, it is shown that this response is comprised of at least three independent components. These include a response to antigens recognized in association with H-2^d products, a response to Qa-1^b-associated antigens which is notH-2-restricted and a response directed toward antigens not associated with either H-2^d- or Qa-1^b-coded determinants. The last response appears to be the weakest of the three. In addition, cells from NZB F₁ mice which were either homozygous (Qa-1 ^a /Qa-1 ^a ) or heterozygous (Qa-1 ^a /Qa-1 ^b ) forQa-1 alleles, all responded to BALB/c cells. These data suggest that the NZB CTL response to BALB/c cells is not solely dependent on antigens coded for by genes in theH-2D-Tla region for either the sensitization or effector phases of the response. The ontogeny of the NZB anti-BALB/c CTL response coincides with that of a number of B-cell abnormalities but is shown in experiments with-suppressed NZB mice to be independent of B-cell dysfunction. Studies with (NZB x B10.D2)F₁ + B10.D2 mice demonstrated that the anti-BALB/cCTL response to antigens coded for outside ofQa-1 is governed by at least two genes. Finally, it is shown that another conventionallyH-2-restricted response, that to TNP-modified isologous cells, is neither significantly cross-reactive nor markedly elevated in NZB mice. — The foregoing observations suggest that some subsets of NZB T lymphocytes are intrinsically abnormal. The possibilities that the apparent hyperreactivity of NZB CTL precursors, evidenced in the response to BALB/c cells, is primary or results from the secondary effects of excess T-cell help are discussed.     

Genetic control of contact sensitivity in mice: Effect ofH-2 and nonH-2 loci

The genetic control of delayed-type hypersensitivity in mice was investigated by contact sensitization with picryl chloride. Distribution patterns of contact sensitivity in 11 inbred strains of mice showed significant differences among strains. Comparison of levels of response between congenic-resistant lines and their inbred partners, at 9 to 11 weeks of age, revealed a clear association betweenH-2 haplotype and the magnitude of response. Testing ofH-2 recombinants further suggested the influence of two genes mapping at either end of theH-2 complex. While theH-2K ^d andH-2D ^k alleles were associated with a high response, theH-2K ^k ,H-2K ^b ,H-2D ^d , andH-2D ^b alleles were associated with a low response. Analysis of the ontogeny of response suggested that theH-2 haplotype manifests its effect through the maturation of contact sensitivity. On both the C57BL/6By and C57BL/10Sn backgrounds, theH-2 ^d haplotype was associated with early maturation of response, while theH-2 ^b haplotype was associated with late maturation. Analysis of the response of congenic lines with different genetic backgrounds and of CXB recombinant-inbred lines further revealed the marked effects of yet other genes on this trait.     

A comparative approach to examine competitive response of 48 wetland plant species

Abstract. Competitive ability can be separated into competitive effect (ability to suppress neighbours) and competitive response (ability to tolerate suppressive effect from neighbours), but little is known about the competitive response of plants. A screening trial was conducted in outdoor plant pots where competitive response was measured for 48 wetland species during four months grown with seven established sward species: Acorus calamus, Carex crinita, Eleocharis smallii, Lythrum salicaria, Penthorum sedoides, Scirpus acutus and Typha angustifolia. Competitive response was calculated as 100 (x₁–x₂)/x₁, where x₁ is the weight of the target plant grown alone and x₂ the weight of the target plant grown in the swards. Despite significant differences in biomass and survivorship of the target plants between the sward species, the correspondence, W, of the rank order of the competitive response of target plants grown in the seven sward species was 0.70 (P < 0.001). The competitive response values were not significantly correlated with independent measures of competitive effect, relative growth rate or functional classification. Published competitive effect values, however, were significantly positively correlated with RGR. The results suggest a different approach towards the study of competitive response, with a conceptual model including three different response types: (1) escape; (2) foraging; and (3) persistence.     

ETB-type receptors mediate endothelin-stimulated contraction in the aortic vascular smooth muscle of the spiny dogfish shark,Squalus acanthias

Using various agonists, and the specific antagonist BQ-123, we have examined the sensitivity to endothelin of the vascular smooth muscle of the ventral aorta of the spiny dogfish shark, Squalus acanthias. Human endothelin-1 produced significant contraction of isolated vascular smooth muscle rings, with an EC₅₀ of 10 nmol·1^-1. The presence of an intact endothelium did not alter this response but the magnitude of the contraction was greater in rings with an intact endothelium. The response to 0.2 mol·1^-1 endothelin-1 was equivalent to that of 0.1 mmol·1^-1 acetylcholine, and significantly greater than that to 80 mmol·1^-1 KCl, suggesting high sensitivity even to the heterologous, mammalian peptide. The Hill plot of the contractile response was a straight line with a slope of 1.12, indicating that a single receptor was mediating the response. Endothelin-1, endothelin-3, and sarafotoxin S6c produced similar concentration-response curves, and the response to endothelin-1 was insensitive to the ET_A-specific inhibitor BQ-123. Our data are consistent with the hypothesis that the receptor involved in the contractile response to endothelin of shark aortic vascular smooth muscle is of the ET_B-rather than the ET_A-type.Abbreviations ACh acetylcholine - ANP atrial natriuretic peptide - CA celiacomesenterie artery - CRC concentration response curve - DMSO dimethylsulphoxide - ET endothelin - STX sarafotoxin - VSM vascular smooth muscle - EDCF endothelium derived contraction factor     

Interaction between the predator Xylocoris sordidus and Bacillus thuringiensis bioinsecticides

Xylocoris species (Hemiptera: Anthocoridae) are known to occur in various habitats and attack a diversity of agriculturally important prey. Other groups of organisms, such as strains of Bacillus thuringiensis Berliner (Bt) bacteria, also have been extensively studied and applied as biological control agents. The use of these Bt-bioinsecticides in association with predators may be a good strategy in integrated pest management. This work had the objective to study predator behaviour, predatory capacity, and functional response of fifth-instar nymphs of Xylocoris sordidus (Reuter) to eggs of Plutella xylostella (L.) (Lepidoptera: Plutellidae) and Corcyra cephalonica (Stainton) (Lepidoptera: Pyralidae) treated with one of three commercial Bt-bioinsecticides. The predator presented a type II functional response to untreated P. xylostella eggs (control) and to eggs treated with Agree, whereas the response was type III to P. xylostella eggs treated with Xentari and Dipel. However, on a diet of C. cephalonica eggs the predator displayed a type II response curve on eggs treated with each of the three bioinsecticides, and a type III response on untreated eggs. Bioinsecticides based on B. thuringiensis may be used in association with X. sordidus predators to control lepidopterous pest species.     

Stomatal responses of C3, C3-C4 and C4Flaveria species to light and intercellular CO2 concentration: implications for the evolution of stomatal behaviour

Stomatal function mediates physiological trade‐offs associated with maintaining a favourable H₂O balance in leaf tissues while acquiring CO₂ as a photosynthetic substrate. The C₃ and C₄ species appear to have different patterns of stomatal response to changing light conditions, and variation in this behaviour may have played a role in the functional diversification of the different photosynthetic pathways. In the current study, we used gain analysis theory to characterize the stomatal conductance response to light intensity in nine different C₃, C₄ and C₃‐C₄ intermediate species Flaveria species. The response of stomatal conductance (g_s) to a change in light intensity represents both a direct (related to a change in incident light intensity, I) and indirect (related to a change in intercellular CO₂ concentration, C_i) response. The slope of the line relating the change in g_s to C_i was steeper in C₄ species, compared with C₃ species, with C₃‐C₄ species having an intermediate response. This response reflects the greater relative contribution of the indirect versus direct component of the g_s versus I response in the C₄ species. The C₃‐C₄ species, Flaveria floridana, exhibited a C₄‐like response whereas the C₃‐C₄ species, Flaveria sonorensis and Flaveria chloraefolia, exhibited C₃‐like responses, similar to their hypothesized position along the evolutionary trajectory of the development of C₄ photosynthesis. There was a positive correlation between the relative contribution of the indirect component of the g_s versus I response and water use efficiency when evaluated across all species. Assuming that the C₃‐C₄ intermediate species reflect an evolutionary progression from fully expressed C₃ ancestors, the results of the current study demonstrate an increase in the contribution of the indirect component of the g_s versus I response as taxa evolve toward the C₄ extreme. The greater relative contribution of the indirect component of the stomatal response occurs through both increases in the indirect stomatal components and through decreases in the direct. Increases in the magnitude of the indirect component may be related to the maintenance of higher water use efficiencies in the intermediate evolutionary stages, before the appearance of fully integrated C₄ photosynthesis.     

The wavy growth 3 E3 ligase family controls the gravitropic response in Arabidopsis roots

Regulation of the root growth pattern is an important control mechanism during plant growth and propagation. To better understand alterations in root growth direction in response to environmental stimuli, we have characterized an Arabidopsis thaliana mutant, wavy growth 3 (wav3), whose roots show a short‐pitch pattern of wavy growth on inclined agar medium. The wav3 mutant shows a greater curvature of root bending in response to gravity, but a smaller curvature in response to light, suggesting that it is a root gravitropism‐enhancing mutation. This wav3 phenotype also suggests that enhancement of the gravitropic response in roots strengthens root tip impedance after contact with the agar surface and/or causes an increase in subsequent root bending in response to obstacle‐touching stimulus in these mutants. WAV3 encodes a protein with a RING finger domain, and is mainly expressed in root tips. RING‐containing proteins often function as an E3 ubiquitin ligase, and the WAV3 protein shows such activity in vitro. There are three genes homologous to WAV3 in the Arabidopsis genome [EMBRYO SAC DEVELOPMENT ARREST 40 (EDA40), WAVH1 and WAVH2 ], and wav3 wavh1 wavh2 triple mutants show marked root gravitropism abnormalities. This genetic study indicates that WAV3 functions positively rather than negatively in root gravitropism, and that enhancement of the gravitropic response in wav3 roots is dependent upon the function of WAVH2 in the absence of WAV3. Hence, our results demonstrate that the WAV3 family of proteins are E3 ligases that are required for root gravitropism in Arabidopsis.     

Gracilaria and its epiphytes: 4. The response of two Gracilaria species to Ulva lactuca in a bacteria-limited environment

The responses of Gracilaria lemaneiformis, an easily epiphytized host,and the relatively resistant G. cornea mutant, to the green alga Ulva lactuca were studied using biculture experiments with and withoutantibiotics. Both Gracilaria species grown with and without U.lactuca showed different levels of growth rate, release of hydrogenperoxide and of halogenated hydrocarbons. These quantitative differencesled to a successful response against Ulva lactuca in the case of G.cornea mutant and to a failure in response in the case of G.lemaneiformis. The response of each Gracilaria species to U.lactuca was qualitatively similar to its response to bacteria. This suggeststhe involvement of oligosaccharide elicitors produced in the presence ofepiphytes and bacteria. A clear Gracilaria inhibition was demonstratedwith extracts of the culture medium. It appears that hydrogen peroxide,halogenated hydrocarbons and oligosaccharides may be components of theinhibitory activity of the extracts. The responses of Gracilaria speciesto the presence of U. lactuca suggest the characterization of adefence response.     

Identification of PprM: a modulator of the PprI-dependent DNA damage response in Deinococcus radiodurans

Deinococcus radiodurans possesses a DNA damage response mechanism that acts via the PprI protein to induce RecA and PprA proteins, both of which are necessary in conferring extreme radioresistance. In an effort to further delineate the nature of the DNA damage response mechanism in D. radiodurans, we set out to identify novel components of the PprI-dependent signal transduction pathway in response to radiation stress. Here we demonstrate the discovery of a novel regulatory protein, PprM (a modulator of the PprI-dependent DNA damage response), which is a homolog of cold shock protein (Csp). Disruption of the pprM gene rendered D. radiodurans significantly sensitive to γ-rays. PprM regulates the induction of PprA but not that of RecA. PprM belongs in a distinct clade of a subfamily together with Csp homologs from D. geothermalis and Thermus thermophilus. Purified PprM is present as a homodimer under physiological conditions, as the case with Escherichia coli CspD. The pprA pprM double-disruptant strain exhibited higher sensitivity than the pprA or pprM single disruptant strains, suggesting that PprM regulates other hitherto unknown protein(s) important for radioresistance besides PprA. This study strongly suggests that PprM is involved in the radiation response mediated by PprI in D. radiodurans.     

Induction of different defences by two enemies in the rotifer Keratella tropica: response priority and sensitivity to enemy density

1. Keratella tropica has qualitatively distinct spine‐development responses to kairomones released by the predatory rotifer Asplanchna and the cladoceran interference competitor Daphnia. Asplanchna induces a fourfold lengthening of the right posterior spine (to c.100 μm), a shortening or loss of the left posterior spine and a lengthening of two pairs of anterior spines. Daphnia induces a moderate elongation of both right and left posterior spines. This study tests three hypotheses regarding the sensitivity of these responses to enemy density, and the response priority when both enemies are present. 2. First, since K. tropica and Brachionus calyciflorus have similarly pronounced and effective spine‐development responses to Asplanchna, with no appreciable demographic cost, they should be similarly sensitive to Asplanchna density. This was the case. Both showed an exponential response to increasing Asplanchna density, well described by an asymptotic exponential regression model, and exhibited 50% maximal spine development at statistically similar Asplanchna densities–2.5 and 1.7 μg dry weight L^?1 (1.8 and 1.2 individuals L^?1), respectively. Strong selection for these Asplanchna‐induced responses clearly has led to a coupling of exuberant and effective morphological defence with an unrivalled sensitivity to predator density. 3. Second, since K. tropica’s response to Daphnia is much less pronounced and effective than its response to Asplanchna, it should be less sensitive to Daphnia density. This hypothesis was supported. Spine development increased linearly with increasing Daphnia density and was 50% maximal at 454 μg dry weight Daphnia L^?1, a biomass density 180 times greater than that inducing a comparable response to Asplanchna. 4. Third, since K. tropica’s response to Daphnia does not reduce Asplanchna predation, K. tropica should respond to Asplanchna when both enemies are present at densities sufficient to induce spine development. This was the case. The presence of Daphnia neither reduced nor increased the length of the right posterior spine; it only limited the extent to which the left spine was reduced or lost.     

Stomatal response to humidity in a sugarcane field: simultaneous porometric and micrometeorological measurements*

Abstract. Gas exchange data obtained with wellventilated leaf cuvettes provide clear evidence of a stomatal response to leaf-air vapour pressure difference (V). In contrast, remotely sensed leaf temperatures with specific assumptions regarding canopy boundary layer characteristics, have been interpreted to mean that stomata do not respond to V. We address this apparent discrepancy in a sugarcane field by simultaneous application of a single-leaf, porometric technique and a whole-canopy, Bowen ratioenergy balance technique. These methods indicated significant stomatal response to V in well-irrigated sugarcane. Stomatal responses to V in the field were obscured by strong covariance of major environmental parameters so that opening responses to light and closing responses to V tended to offset each other. Low boundary layer conductance significantly uncoupled V at the leaf surface (V_s) from V determined in the bulk atmosphere (V_a). This reduced the range of the stimulus, V_s, thereby reducing the range of the stomatal response, without indicating low stomatal sensitivity to V. Stomatal responses to V_a may be smaller than expected from V response curves in cuvettes, since V_s rather than the conventionally measured V_a is analogous to V in a well-stirred cuvette. Recently published conclusions that remotely sensed canopy temperatures are inconsistent with stomatal response to V may be based on erroneous estimates of canopy boundary layer conductance and thus of V_s, use of air saturation deficit rather than V to express evaporative demand, and investigation at higher levels of evaporative demand than those eliciting maximal stomatal response.     

Phototactic behaviour in Aphidius gifuensis (Hymenoptera:Braconidae)

We investigated the spectral sensitivity and response to light intensity of Aphidius gifuensis (Hymenoptera: Braconidae), a key natural enemy of the green peach aphid, Myzus persicae (Hemiptera: Aphididae). We used 15 monochromatic lights (emitting various specific wavelengths from 340 to 689 nm) and white light. Monochromatic light of different wavelengths and white light elicited photopositive behaviour from A. gifuensis. The strongest response was stimulated by blue light (492 nm), which induced a movement of 43.5 cm, a response that differed from all other groups. This was followed by green light (568 nm) and UV-light (380 nm). There was no significant response to orange light (601 nm) or red light (649, 668 and 689 nm) from A. gifuensis. The response intensity curve for A. gifuensis to monochromatic light (492 nm) decreased as light intensity increased. At 568 nm, the phototactic response showed an ‘S’ shaped curve. But at 628 nm, the phototactic response rose continuously with increasing intensity. We report here that the visual system of A. gifuensis is composed of three spectrum receptors, attuned to UV, blue and green light. While light intensity is a key factor in determining the photopositive response of A. gifuensis, the effect of intensity varies by wavelength.