Sensitivity of DF-ICP-MS, PERALS and alpha-spectrometry for the determination of actinides: A comparison

We applied three techniques (DF-ICP-MS, PERALS and alpha-spectrometry) for the determination of minor actinides at environmental levels. For each method the limit of detection and the resolution were estimated in order to study the content and isotopic composition of the actinides. Two international reference materials, IAEA-135 (Irish Sea Sediment) and IAEA-300 (Baltic Sea sediment) were analyzed for activity concentrations of 238Pu, 239Pu, 240Pu, 241Pu and 241Am. The sensitivities of the three determination techniques were compared.

Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel

Gastro-intestinal nematodes in ruminants, especially Haemonchus contortus, are a global threat to sheep and cattle farming. The emergence of drug resistance, and even multi-drug resistance to the currently available classes of broad spectrum anthelmintics, further stresses the need for new drugs active against gastro-intestinal nematodes. A novel chemical class of synthetic anthelmintics, the Amino-Acetonitrile Derivatives (AADs), was recently discovered and the drug candidate AAD-1566 (monepantel) was chosen for further development. Studies with Caenorhabditis elegans suggested that the AADs act via nicotinic acetylcholine receptors (nAChR) of the nematode-specific DEG-3 subfamily. Here we identify nAChR genes of the DEG-3 subfamily from H. contortus and investigate their role in AAD sensitivity. Using a novel in vitro selection procedure, mutant H. contortus populations of reduced sensitivity to AAD-1566 were obtained. Sequencing of full-length nAChR coding sequences from AAD-susceptible H. contortus and their AAD-1566-mutant progeny revealed 2 genes to be affected. In the gene monepantel-1 (Hco-mptl-1, formerly named Hc-acr-23H), a panel of mutations was observed exclusively in the AAD-mutant nematodes, including deletions at intron-exon boundaries that result in mis-spliced transcripts and premature stop codons. In the gene Hco-des-2H, the same 135 bp insertion in the 5' UTR created additional, out of frame start codons in 2 independent H. contortus AAD-mutants. Furthermore, the AAD mutants exhibited altered expression levels of the DEG-3 subfamily nAChR genes Hco-mptl-1, Hco-des-2H and Hco-deg-3H as quantified by real-time PCR. These results indicate that Hco-MPTL-1 and other nAChR subunits of the DEG-3 subfamily constitute a target for AAD action against H. contortus and that loss-of-function mutations in the corresponding genes may reduce the sensitivity to AADs.

United we stand, divided we fall: a meta-analysis of experiments on clonal integration and its relationship to invasiveness

Fragmentation and vegetative regeneration from small fragments may contribute to population expansion, dispersal and establishment of new populations of introduced plants. However, no study has systematically tested whether a high capacity of vegetative regeneration is associated with a high degree of invasiveness. For small single-node fragments, the presence of internodes may increase regeneration capacity because internodes may store carbohydrates and proteins that can be used for regeneration. We conducted an experiment with 39 stoloniferous plant species to examine the regeneration capacity of small, single-node fragments with or without attached stolon internodes. We asked (1) whether the presence of stolon internodes increases regeneration from single-node fragments, (2) whether regeneration capacity differs between native and introduced species in China, and (3) whether regeneration capacity is positively associated with plant invasiveness at a regional scale (within China) and at a global scale. Most species could regenerate from single-node fragments, and the presence of internodes increased regeneration rate and subsequent growth and/or asexual reproduction. Regeneration capacity varied greatly among species, but showed no relationship to invasiveness, either in China or globally. High regeneration capacity from small fragments may contribute to performance of clonal plants in general, but it does not appear to explain differences in invasiveness among stoloniferous clonal species.

Root Foraging Increases Performance of the Clonal Plant Potentilla reptans in Heterogeneous Nutrient Environments

Background Plastic root-foraging responses have been widely recognized as an important strategy for plants to explore heterogeneously distributed resources. However, the benefits and costs of root foraging have received little attention. Methodology/Principal Findings In a greenhouse experiment, we grew pairs of connected ramets of 22 genotypes of the stoloniferous plant Potentilla reptans in paired pots, between which the contrast in nutrient availability was set as null, medium and high, but with the total nutrient amount kept the same. We calculated root-foraging intensity of each individual ramet pair as the difference in root mass between paired ramets divided by the total root mass. For each genotype, we then calculated root-foraging ability as the slope of the regression of root-foraging intensity against patch contrast. For all genotypes, root-foraging intensity increased with patch contrast and the total biomass and number of offspring ramets were lowest at high patch contrast. Among genotypes, root-foraging intensity was positively related to production of offspring ramets and biomass in the high patch-contrast treatment, which indicates an evolutionary benefit of root foraging in heterogeneous environments. However, we found no significant evidence that the ability of plastic foraging imposes costs under homogeneous conditions (i.e. when foraging is not needed). Conclusions/Significance Our results show that plants of P. reptans adjust their root-foraging intensity according to patch contrast. Moreover, the results show that the root foraging has an evolutionary advantage in heterogeneous environments, while costs of having the ability of plastic root foraging were absent or very small.

Genetic diversity among Mycoplasma species bovine group 7: clonal isolates from an outbreak of polyarthritis, mastitis, and abortion in dairy cattle

A comprehensive genetic analysis of 60 Mycoplasma sp. bovine group 7 isolates from different geographic origins and epidemiological settings is presented. Twenty-four isolates were recovered from the joints of calves during sporadic episodes of polyarthritis in geographically distinct regions of Queensland and New South Wales, Australia, including two clones of the type strain PG5O. A further three Australian isolates were also recovered from the tympanic bulla, retropharyngeal lymph node and the lung and another three isolates had unconfirmed histories. Six isolates originated from Germany, Portugal, Nigeria, and France. Twenty-four epidemiologically related isolates of Mycoplasma sp. bovine group 7 were recovered from multiple tissue sites and body fluids of infected calves with polyarthritis, mastitic milk, and from the stomach contents, lung and liver from aborted foetuses in three large, centrally managed dairy herds in New South Wales, Australia. Restriction endonuclease analysis (REA) of genomic DNA differentiated 29 Cfol profiles among these 60 isolates and grouped all 24 epidemiologically related isolates in a defined pattern showing a clonal origin. Three isolates of this clonal cluster were recovered from mastitic milk and the synovial exudate of clinically-affected calves and appeared sporadically for periods up to 18 months after the initial outbreak of polyarthritis indicating a persistent, close association of the organism with cattle in these herds. The Cfol profile representative of the clonal cluster was distinguishable from profiles of isolates recovered from multiple, unrelated cases of polyarthritis in Queensland and New South Wales and from other countries. All 24 isolates from the clonal cluster possessed a plasmid (pBG7AU) with a molecular size of 1022 bp. DNA sequence analysis of pBG7AU identified two open reading frames sharing 81 and 99% DNA sequence similarity with hypothetical replication control proteins A and B respectively, previously described in plasmid pADB201 isolated from M. mycoides subspecies mycoides. Other isolates of bovine group 7, epidemiologically unrelated to the clonal cluster, including two clones of the type strain PG5O, possessed a similar-sized plasmid. These data confirm that Mycoplasma sp. bovine group 7 is capable of migrating to, and multiplying within, different tissue sites within a single animal and among different animals within a herd.

Variation of a test's sensitivity and specificity with disease prevalence

BACKGROUND Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. METHODS We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. RESULTS Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. INTERPRETATION The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

ANOVA kernels and RKHS of zero mean functions for model-based sensitivity analysis

Given a reproducing kernel Hilbert space (H,〈.,.〉)(H,〈.,.〉) of real-valued functions and a suitable measure μμ over the source space D⊂RD⊂R, we decompose HH as the sum of a subspace of centered functions for μμ and its orthogonal in HH. This decomposition leads to a special case of ANOVA kernels, for which the functional ANOVA representation of the best predictor can be elegantly derived, either in an interpolation or regularization framework. The proposed kernels appear to be particularly convenient for analyzing the effect of each (group of) variable(s) and computing sensitivity indices without recursivity.

Invasive clonal plant species have a greater root-foraging plasticity than non-invasive ones

Clonality is frequently positively correlated with plant invasiveness, but which aspects of clonality make some clonal species more invasive than others is not known. Due to their spreading growth form, clonal plants are likely to experience spatial heterogeneity in nutrient availability. Plasticity in allocation of biomass to clonal growth organs and roots may allow these plants to forage for high-nutrient patches. We investigated whether this foraging response is stronger in species that have become invasive than in species that have not. We used six confamilial pairs of native European clonal plant species differing in invasion success in the USA. We grew all species in large pots under homogeneous or heterogeneous nutrient conditions in a greenhouse, and compared their nutrient-foraging response and performance. Neither invasive nor non-invasive species showed significant foraging responses to heterogeneity in clonal growth organ biomass or in aboveground biomass of clonal offspring. Invasive species had, however, a greater positive foraging response in terms of root and belowground biomass than non-invasive species. Invasive species also produced more total biomass. Our results suggest that the ability for strong root foraging is among the characteristics promoting invasiveness in clonal plants.

Suppression of OCT4B enhances sensitivity of lung adenocarcinoma A549 cells to cisplatin via increased apoptosis

BACKGROUND Resistance to chemotherapy in lung adenocarcinoma remains a major obstacle. We examined the potential role of Octamer-binding transcription factor-4B (OCT4B) in enhancing sensitivity of lung adenocarcinoma cells to cisplatin. MATERIALS AND METHODS RNAi interference was used to examine the role of OCT4B in cisplatin-treated A549 cells. Cells were transfected with OCT4B siRNA prior to a 48-h cisplatin treatment. Propidium iodide (PI) and caspase-3 staining were used to determine cell viability and apoptosis. Cell-cycle analysis was performed to evaluate alterations in phase distribution. RESULTS OCT4B suppression in cells increased the number of non-viable, PI(+), and apoptotic, caspase-3(+) cells in the presence and absence of cisplatin treatment. Importantly, cisplatin treatment of OCT4B-suppressed cells resulted in a marked transition of cells from G0/G1 to G2/M phase. CONCLUSION Silencing of OCT4B confers sensitivity to cisplatin treatment in A549 cells via cell-cycle regulation, increased proliferation and enhancement of cisplatin-induced apoptosis. OCT4B clearly protects A549 cells from apoptosis.

Splitting of a prevalent Mycobacterium bovis spoligotype by variable-number tandem-repeat typing reveals high heterogeneity in an evolving clonal group

Mycobacterium bovis populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115 M. bovis isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by M. bovis SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.

Aerobic exercise but not resistance exercise reduces intrahepatic lipid content and visceral fat and improves insulin sensitivity in obese adolescent girls: a randomized controlled trial

It is unclear whether regular exercise alone (no caloric restriction) is a useful strategy to reduce adiposity and obesity-related metabolic risk factors in obese girls. We examined the effects of aerobic (AE) vs. resistance exercise (RE) alone on visceral adipose tissue (VAT), intrahepatic lipid, and insulin sensitivity in obese girls. Forty-four obese adolescent girls (BMI ≥95th percentile, 12-18 yr) with abdominal obesity (waist circumference 106.5 ± 11.1 cm) were randomized to 3 mo of 180 min/wk AE (n = 16) or RE (n = 16) or a nonexercising control group (n = 12). Total fat and VAT were assessed by MRI and intrahepatic lipid by proton magnetic resonance spectroscopy. Intermuscular AT (IMAT) was measured by CT. Insulin sensitivity was evaluated by a 3-h hyperinsulinemic (80 mU·m(2)·min(-1)) euglycemic clamp. Compared with controls (0.13 ± 1.10 kg), body weight did not change (P > 0.1) in the AE (-1.31 ± 1.43 kg) and RE (-0.31 ± 1.38 kg) groups. Despite the absence of weight loss, total body fat (%) and IMAT decreased (P < 0.05) in both exercise groups compared with control. Compared with control, significant (P < 0.05) reductions in VAT (Δ-15.68 ± 7.64 cm(2)) and intrahepatic lipid (Δ-1.70 ± 0.74%) and improvement in insulin sensitivity (Δ0.92 ± 0.27 mg·kg(-1)·min(-1) per μU/ml) were observed in the AE group but not the RE group. Improvements in insulin sensitivity in the AE group were associated with the reductions in total AT mass (r = -0.65, P = 0.02). In obese adolescent girls, AE but not RE is effective in reducing liver fat and visceral adiposity and improving insulin sensitivity independent of weight loss or calorie restriction.