Divergence In Sensitivity Research Articles

Cloning and Characterization of Trypanosoma congolense and T. vivax Nucleoside Transporters Reveal the Potential of P1-Type Carriers for the Discovery of Broad-Spectrum Nucleoside-Based Therapeutics against Animal African Trypanosomiasis.

African Animal Trypanosomiasis (AAT), caused predominantly by Trypanosoma brucei brucei, T. vivax and T. congolense, is a fatal livestock disease throughout Sub-Saharan Africa. Treatment options are very limited and threatened by resistance. Tubercidin (7-deazaadenosine) analogs have shown activity against individual parasites but viable chemotherapy must be active against all three species. Divergence in sensitivity to nucleoside antimetabolites could be caused by differences in nucleoside transporters. Having previously characterized the T. brucei nucleoside carriers, we here report the functional expression and characterization of the main adenosine transporters of T. vivax (TvxNT3) and T. congolense (TcoAT1/NT10), in a Leishmania mexicana cell line ('SUPKO') lacking adenosine uptake. Both carriers were similar to the T. brucei P1-type transporters and bind adenosine mostly through interactions with N3, N7 and 3'-OH. Expression of TvxNT3 and TcoAT1 sensitized SUPKO cells to various 7-substituted tubercidins and other nucleoside analogs although tubercidin itself is a poor substrate for P1-type transporters. Individual nucleoside EC50s were similar for T. b. brucei, T. congolense, T. evansi and T. equiperdum but correlated less well with T. vivax. However, multiple nucleosides including 7-halogentubercidines displayed pEC50>7 for all species and, based on transporter and anti-parasite SAR analyses, we conclude that nucleoside chemotherapy for AAT is viable.

Revisiting the functional significance of binocular cues for perceiving motion-in-depth

Binocular differencing of spatial cues required for perceiving depth relationships is associated with decreased sensitivity to the corresponding retinal image displacements. However, binocular summation of contrast signals increases sensitivity. Here, we investigated this divergence in sensitivity by making direct neural measurements of responses to suprathreshold motion in human adults and 5-month-old infants using steady-state visually evoked potentials. Interocular differences in retinal image motion generated suppressed response functions and correspondingly elevated perceptual thresholds compared to motion matched between the two eyes. This suppression was of equal strength for horizontal and vertical motion and therefore not specific to the perception of motion-in-depth. Suppression is strongly dependent on the presence of spatial references in the image and highly immature in infants. Suppression appears to be the manifestation of a succession of spatial and interocular opponency operations that occur at an intermediate processing stage either before or in parallel with the extraction of motion-in-depth.

Comparative studies of groundwater vulnerability assessment

Pollution of groundwater is a primary issue because aquifers are susceptible to contamination from land use and anthropogenic impacts. Groundwater susceptibility is intrinsic and specific. Intrinsic vulnerability refers to an aquifer that is susceptible to pollution and to the geological and hydrogeological features. Vulnerability assessment is an essential step in assessing groundwater contamination. This approach provides a visual analysis for helping planners and decision makers to achieve the sustainable management of water resources. Comparative studies are applying different methodologies to result in the basic evaluation of the groundwater vulnerability. Based on the comparison of methods, there are several advantages and disadvantages. SI can be overlaid on DRASTIC and Pesticide DRASTIC to extract the divergence in sensitivity. DRASTIC identifies low susceptibility and underestimates the pollution risk while Pesticide DRASTIC and SI represents better risk and is recommended for the future. SINTACS method generates very high vulnerability zones with surface waters and aquifer interactions. GOD method could be adequate for vulnerability mapping in karstified carbonate aquifers at small–moderate scales, and EPIK method can be used for large scale. GOD method is suitable for designing large area such as land management while DRASTIC has good accuracy and more real use in geoenvironmental detailed studies.

Rapid and Parallel Adaptive Evolution of the Visual System of Neotropical Midas Cichlid Fishes.

Midas cichlid fish are a Central American species flock containing 13 described species that has been dated to only a few thousand years old, a historical timescale infrequently associated with speciation. Their radiation involved the colonization of several clear water crater lakes from two turbid great lakes. Therefore, Midas cichlids have been subjected to widely varying photic conditions during their radiation. Being a primary signal relay for information from the environment to the organism, the visual system is under continuing selective pressure and a prime organ system for accumulating adaptive changes during speciation, particularly in the case of dramatic shifts in photic conditions. Here, we characterize the full visual system of Midas cichlids at organismal and genetic levels, to determine what types of adaptive changes evolved within the short time span of their radiation. We show that Midas cichlids have a diverse visual system with unexpectedly high intra- and interspecific variation in color vision sensitivity and lens transmittance. Midas cichlid populations in the clear crater lakes have convergently evolved visual sensitivities shifted toward shorter wavelengths compared with the ancestral populations from the turbid great lakes. This divergence in sensitivity is driven by changes in chromophore usage, differential opsin expression, opsin coexpression, and to a lesser degree by opsin coding sequence variation. The visual system of Midas cichlids has the evolutionary capacity to rapidly integrate multiple adaptations to changing light environments. Our data may indicate that, in early stages of divergence, changes in opsin regulation could precede changes in opsin coding sequence evolution.

Significant Divergence in Sensitivity to Antimalarial Drugs between Neighboring Plasmodium falciparum Populations along the Eastern Border of Myanmar.

Malaria parasites in different areas where malaria is endemic display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to 10 drugs. Despite their close proximity, the Kachin parasites displayed higher 50% inhibitory concentrations than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine, and dihydroartemisinin. Genotyping of genes associated with drug resistance also showed significant differences in the prevalence rates of mutant alleles between the two regions. Particularly, major pfdhfr mutations mediating pyrimethamine resistance and the pfdhps A437G mutation had significantly higher frequencies in the Kachin parasites (P < 0.005). Moreover, when pfdhfr and pfdhps were considered together, the wild-type allele was found only in the Wa samples (22.6%). In addition, the pfmdr1 Y184F mutation reached 38.7% in the Kachin parasites, compared to 9.7% in the Wa parasites, whereas N86Y was only detected in the Wa parasites, at 22.6%. Furthermore, the F446I mutation and all mutations in the propeller domain of the PfK13 gene were significantly more frequent in the Kachin parasites. Collectively, this work demonstrates that even in spatially closely separated regions, parasites can exhibit drastic differences in drug sensitivities and genetic makeups underlying drug resistance, which may reflect regionally different drug histories and genetic drift of these isolated parasite populations.

Seasonal divergence in the sensitivity of evapotranspiration to climate and vegetation growth in the Yellow River Basin, China

AbstractSeasonal variations in terrestrial evapotranspiration (ET) in the Yellow River Basin (YRB) have crucial impacts on the seasonal trajectories of the regional water cycle, vegetation growth, and local climate feedback. However, the possibly divergent roles of climate and vegetation growth variations in controlling seasonal ET patterns remain poorly quantified. This study therefore quantifies the interannual sensitivity and attribution of ET to climate and vegetation growth variations in different seasons and different biomes in the YRB in China between 1982 and 2011, using the satellite‐derived normalized difference vegetation index (NDVI), FLUXNET‐based upscaled ET, and concurrent climate data. The results reveal a clear seasonal divergence in the interannual sensitivity of ET to climate and vegetation growth variations in the YRB. Interannual precipitation and NDVI variations play a dominant role in controlling seasonal ET variations in the YRB, with temperature having a marginal effect. Interannual ET sensitivity to precipitation weakens with an increasing mean annual precipitation gradient in almost all seasons, especially in summer and autumn. More importantly, a seasonally varying role of vegetation growth in mediating seasonal ET was discovered, and a crucial role of late‐growing‐season vegetation growth in controlling the seasonal trajectory of regional ET was explicitly identified. These results suggest that ongoing intensive vegetation restoration has crucial impacts on seasonal water‐cycle patterns and consequent terrestrial‐atmospheric biogeochemical feedback in the YRB.

Simple, rapid, inexpensive platform for the diagnosis of malaria by loop mediated isothermal amplification (LAMP)

We attempted to improve the loop-mediated isothermal amplification (LAMP) method for malaria diagnosis by using a simple DNA extraction procedure, and a portable device performing both the amplification and detection of LAMP in one platform. Additionally, the device served as a heating block for the DNA preparation. We refer this method as LAMP-Tube scanner, and evaluated using 209 microscopically positive malaria samples and compared them to RDTs and LAMP-Thermocycler. Two most common human infecting Plasmodium species were detected. The LAMP-Tube scanner method is found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was closely less than 60min. Sensitivity and specificity of LAMP-Tube scanner in detecting Plasmodium falciparum were 95% and 93.3%, compared to microscopy and 98.3% and 100% respectively, compared to standard LAMP-Thermocycler. In addition, it showed a detection limit of 10 and 40 copies of the parasitemia for Plasmodium vivax and P. falciparum. Accordingly, in comparison to the results obtained by microscopy, the LAMP-Tube scanner had a less divergence in sensitivity and specificity, and yielded results similar to those of LAMP-Thermocycler. This method has the great potential as a field usable molecular tool for the diagnosis of malaria and is an alternative to conventional PCR-based diagnostic methods for field use.

Assessing resistance to head blight in wheat cultivars inoculated with different Fusarium isolates

Four winter wheat cultivars, differing in resistance to Fusarium head blight (FHB), were spray inoculated under field conditions for three years with 18 isolates of two Fusarium species (F. graminearum and F. culmorum) obtained from different regions of the Czech Republic. Deoxynivalenol (DON) contamination, FHB severity (VSS), Fusarium damaged kernels (FDK) and reductions of thousand grain weight and grain weight per spike were measured to describe the aggressiveness level of isolates. Highly significant correlations were found between these traits, but correlation coefficients ranged from 0.45 to 0.99. Analyses of variance showed significant effects of year, cultivar, isolate and Fusarium species on all traits. Experimental year accounted for the highest proportion of variation (37&amp;ndash;59%), followed by cultivar (11&amp;ndash;39%), isolate (9&amp;ndash;18%) and species (1&amp;ndash;3%). Two-way and three-way interactions between the main factors were also statistically significant, but with generally lower contribution to total variation. Though the examined isolates of two Fusarium species differed largely in quantitative aggressiveness, they did not show any evident qualitative differences in virulence. Pathogenic specialization of isolates was relatively higher in FDK. This trait appeared to be less affected by the disease level than the content of DON, which strongly reflected environmental conditions, cultivar resistance and pathogenicity of an isolate. Under highly variable weather conditions the significance of differences between the cultivars was not often detected by a single isolate and it was necessary to look for isolate groups in order to get a higher percentage of significant differences and prove the moderate resistance of the cultivar Arina. The highest number of significant differences between the cultivars was reached after selection of isolates, the application of which resulted in pronounced cultivar effects (lower interaction with years) and which showed high correspondence with the average reaction of cultivars in different years (R&lt;sup&gt;2&lt;/sup&gt;). Divergence in sensitivity to the environment could be another criterion for selecting sources of inoculum.

Antioxidants in blood from sheep lines divergently selected for facial eczema resistance

Romney sheep have been evaluated for resistance to facial eczema (FE) using a process which involves challenge with the FE toxin, sporidesmin, and they have been bred in selection lines for increased resistance (R) or susceptibility (S) to FE. There is evidence that sporidesmin exerts its toxic effects by generating reactive oxygen species, and protection can be afforded by a number of antioxidants and antioxidant enzymes. Our objective was to summarise three separate experiments to determine whether the R and S lines differed in antioxidant mechanisms, in search of a non‐invasive genetic marker. Lines were compared for the activities of four enzymes in blood in Experiment 1, superoxide dismutase (SOD), catalase (CAT), glu‐tathione peroxidase (GPX), and glutathione reduct‐ase (GR), and for the concentration of the tri‐peptide thiol, glutathione (GSH). SOD, CAT, and GSH were also recorded in Experiment 2, and GPX alone in Experiment 3. Heritabilities were estimated for SOD, CAT, and GSH. SOD activity was lower and CAT activity was higher in the R than in the S line (P < 0.01 for both enzymes). GPX activity was higher in the R than in the S line in Experiment 1 (P = 0.002) and Experiment 3 (P = 0.06), whilst neither GR activity nor GSH concentration differed significantly between lines. Heritability estimates for SOD, CAT, and GSH were 0.19 ± 0.11, 0.63 ± 0.14, and 0.34 ± 0.14, respectively. It is concluded that selection for divergence in sensitivity to sporidesmin in sheep may have been successful partly because of correlated responses in activities of three antioxidant enzymes (SOD, CAT, and GPX), capable of scavenging reactive oxygen species. However, the divergence between resistant and susceptible sheep in blood antioxidant activity was not large enough to be a reliable indicator of individual FE resistance.

Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries.

The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic responses upon pressure steps, resulting from an increase in calcium in combination with a high contractile element calcium sensitivity. Y-27632, believed to be a specific p160ROCK inhibitor, caused concentration-dependent inhibition of basal tone, with near full inhibition at 3 microM. At this concentration, myogenic responses were absent and stepwise pressure elevation resulted in severe vascular distension. Y-27632 did not affect pressure-induced changes in intracellular calcium but rather reduced pressure-induced as well as phenylephrine-induced calcium sensitisation. Thus in the presence of the blocker, for a given calcium concentration, tone was greatly reduced, and the divergence in sensitivity between pressure and phenylephrine as stimuli on the one hand and potassium on the other disappeared. K+ (125 mM) and ionomycin still caused contraction in the presence of the p160ROCK blocker. These data show that in pressurised small arteries the Rho-p160ROCK pathway is active in the absence of vasoconstrictors, keeping the vessels in a state of high calcium sensitivity and basal tone.