Differential allocation and deployment of direct and indirect defences by Vicia sepium along elevation gradients

Dissecting drivers of plant defence investment remains central for understanding the assemblage of communities across different habitats. There is increasing evidence that direct defence strategies against herbivores, including secondary metabolites production, differ along ecological gradients in response to variation in biotic and abiotic conditions. In contrast, intraspecific variation in indirect defences remains unexplored. Here, we investigated variation in herbivory rate, resistance to herbivores, and indirect defences in ant-attracting Vicia species along the elevation gradient of the Alps. Specifically, we compared volatile organic compounds (VOCs) and ant attraction in high and low elevation ecotypes. Consistent with adaptation to the lower herbivory conditions that we detected at higher elevations in the field, high elevation plants were visited by fewer ants and were more susceptible to herbivore attack. In parallel, constitutive volatile organic compound production and subsequent ant attraction were lower in the high elevation ecotypes. We observed an elevation-driven trade-off between constitutive and inducible production of VOCs and ant attraction along the environmental cline. At higher elevations, inducible defences increased, while constitutive defence decreased, suggesting that the high elevation ecotypes compensate for lower indirect constitutive defences only after herbivore attack. Synthesis. Overall, direct and indirect defences of plants vary along elevation gradients. Our findings show that plant allocation to defences are subject to trade-offs depending on local conditions, and point to a feedback mechanism linking local herbivore pressure, predator abundance and the defence investment of plants.

Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent blood exposures in patients with solid tumours.

Patient's preference is for oral chemotherapy when both oral and i.v. are available, provided that efficacy is equivalent. Reliable switch from oral to i.v. is possible if correspondence between respective doses has been established. Vinorelbine oral was developed as a line extension of VRL i.v. on the basis that similar AUCs result in similar activities. From a first crossover study on 24 patients receiving VRL 25 mg/m2 i.v. and 80 mg/m2 oral data extrapolation concluded on AUCs bioequivalence between Vinorelbine 30 mg/m2 i.v. and 80 mg/m2 oral. A new trial was performed to support this calculation. In a crossover design study on patients (PS 0-1) with advanced solid tumours (44% breast carcinoma), VRL was administered (30 mg/m2 i.v., 80 mg/m2 oral) with a standard meal and 5-HT3 antagonists, at 2 weeks interval. Pharmacokinetics was performed over 168 h and VRL was measured by LC-MS/MS. Statistics included bioequivalence tests. Forty-eight patients were evaluable for PK: median age 58 years (25-71), PS0/PS1: 20/28, M/F: 11/37. Mean AUCs were 1,230 +/- 290 and 1,216 +/- 521 ng/ml for i.v. and oral, respectively. The confidence interval of the AUC ratio (0.83-1.03) was within the required regulatory range (0.8-1.25) and proved the bioequivalence between the two doses. The absolute bioavailability was 37.8 +/- 16.0%, and close to the value from the first study (40%). Patient tolerability was globally comparable between both forms with no significant difference on either haematological or non-haematological toxicities (grade 3-4). This new study, conducted on a larger population, confirmed the reliable dose correspondence previously established between vinorelbine 80 mg/m2 oral and 30 mg/m2 i.v.

The Interleukin-1 receptor antagonist is a direct target gene of PPARalpha in liver.

BACKGROUND/AIMS: The Peroxisome Proliferator-Activated Receptor (PPAR) alpha belongs to the superfamily of Nuclear Receptors and plays an important role in numerous cellular processes, including lipid metabolism. It is known that PPARalpha also has an anti-inflammatory effect, which is mainly achieved by down-regulating pro-inflammatory genes. The objective of this study was to further characterize the role of PPARalpha in inflammatory gene regulation in liver. RESULTS: According to Affymetrix micro-array analysis, the expression of various inflammatory genes in liver was decreased by treatment of mice with the synthetic PPARalpha agonist Wy14643 in a PPARalpha-dependent manner. In contrast, expression of Interleukin-1 receptor antagonist (IL-1ra), which was acutely stimulated by LPS treatment, was induced by PPARalpha. Up-regulation of IL-1ra by LPS was lower in PPARalpha -/- mice compared to Wt mice. Transactivation and chromatin immunoprecipitation studies identified IL-1ra as a direct positive target gene of PPARalpha with a functional PPRE present in the promoter. Up-regulation of IL-1ra by PPARalpha was conserved in human HepG2 hepatoma cells and the human monocyte/macrophage THP-1 cell line. CONCLUSIONS: In addition to down-regulating expression of pro-inflammatory genes, PPARalpha suppresses the inflammatory response by direct up-regulation of genes with anti-inflammatory properties.

Decision-theoretic analysis of forensic sampling criteria using Bayesian decision networks

Sampling issues represent a topic of ongoing interest to the forensic science community essentially because of their crucial role in laboratory planning and working protocols. For this purpose, forensic literature described thorough (Bayesian) probabilistic sampling approaches. These are now widely implemented in practice. They allow, for instance, to obtain probability statements that parameters of interest (e.g., the proportion of a seizure of items that present particular features, such as an illegal substance) satisfy particular criteria (e.g., a threshold or an otherwise limiting value). Currently, there are many approaches that allow one to derive probability statements relating to a population proportion, but questions on how a forensic decision maker - typically a client of a forensic examination or a scientist acting on behalf of a client - ought actually to decide about a proportion or a sample size, remained largely unexplored to date. The research presented here intends to address methodology from decision theory that may help to cope usefully with the wide range of sampling issues typically encountered in forensic science applications. The procedures explored in this paper enable scientists to address a variety of concepts such as the (net) value of sample information, the (expected) value of sample information or the (expected) decision loss. All of these aspects directly relate to questions that are regularly encountered in casework. Besides probability theory and Bayesian inference, the proposed approach requires some additional elements from decision theory that may increase the efforts needed for practical implementation. In view of this challenge, the present paper will emphasise the merits of graphical modelling concepts, such as decision trees and Bayesian decision networks. These can support forensic scientists in applying the methodology in practice. How this may be achieved is illustrated with several examples. The graphical devices invoked here also serve the purpose of supporting the discussion of the similarities, differences and complementary aspects of existing Bayesian probabilistic sampling criteria and the decision-theoretic approach proposed throughout this paper.

Bacillus thuringiensis: fermentation process and risk assessment: a short review

Several factors make the local production of Bacillus thuringiensis (Bt) highly appropriate for pest control in developing nations. Bt can be cheaply produced on a wide variety of low cost, organic substrates. Local production results in considerable savings in hard currency which otherwise would be spent on importation of chemical and biological insecticides. The use of Bt in Brazil has been limited in comparison with chemical insecticides. Although Bt is imported, some Brazilian researchers have been working on its development and production. Fermentation processes (submerged and semi-solid) were applied, using by-products from agro-industries. As the semi-solid fermentation process demonstrated to be interesting for Bt endotoxins production, it could be adopted for small scale local production. Although promising results had been achieved, national products have not been registered due to the absence of a specific legislation for biological products. Effective actions are being developed in order to solve this gap. Regardless of the biocontrol agents being considered atoxic and harmless to the environment, information related to direct and indirect effects of microbials are still insufficient in many cases. The risk analysis of the use of microbial control agents is of upmost importance nowadays, and is also discussed.

Large multi-gene phylogenetic trees of the grasses (Poaceae): progress towards complete tribal and generic level sampling.

In this paper we included a very broad representation of grass family diversity (84% of tribes and 42% of genera). Phylogenetic inference was based on three plastid DNA regions rbcL, matK and trnL-F, using maximum parsimony and Bayesian methods. Our results resolved most of the subfamily relationships within the major clades (BEP and PACCMAD), which had previously been unclear, such as, among others the: (i) BEP and PACCMAD sister relationship, (ii) composition of clades and the sister-relationship of Ehrhartoideae and Bambusoideae + Pooideae, (iii) paraphyly of tribe Bambuseae, (iv) position of Gynerium as sister to Panicoideae, (v) phylogenetic position of Micrairoideae. With the presence of a relatively large amount of missing data, we were able to increase taxon sampling substantially in our analyses from 107 to 295 taxa. However, bootstrap support and to a lesser extent Bayesian inference posterior probabilities were generally lower in analyses involving missing data than those not including them. We produced a fully resolved phylogenetic summary tree for the grass family at subfamily level and indicated the most likely relationships of all included tribes in our analysis.

"Silence... Nous sommes en direct avec Allah". Réflexions sur l'émergence d'intervenants musulmans en contexte carcéral.

L'accompagnement spirituel dans les prisons suisses est dominé par un modèle monoculturel d'inspiration chrétienne. Or, la présence importante de détenus de confession musulmane dans les établissements pénitentiaires incitent ceux-ci à organiser un soutien spirituel adapté à cette catégorie de leur population. Dans quel cadre légal cet accompagnement spirituel se déroule-t-il? Quelle forme prend-il ? Quels sont ceux (et plus rarement celles) qui assistent spirituellement les détenus musulmans ? Cet article propose de répondre à ces questions en énonçant les principes juridiques relatifs à l'exercice de la religion en contexte carcéral. Puis, sur la base de matériaux qualitatifs et quantitatif, il présente cinq profils d'intervenants musulmans de prison : l'imam, l'aumônier, le grand-frère, le médiateur et le visiteur.

The use of polyvinyl alcohol glutaraldehyde as solid-phase in ELISA for plague

Discs of polyvinyl alcohol cross-linked with glutaraldehyde were synthesized under acid catalysis (H2SO4). Then, the antigen F1 purified from Yersinia pestis was covalently linked to this modified polymer. Afterwards, an enzyme-linked immunosorbent assay (ELISA) was established for the diagnosis of plague in rabbit and human. The best conditions for the method were achieved by using 1.3 ¼g of F1 prepared in 0.067 M phosphate buffer, pH 7.2, containing 1 M NaCl (PBS); anti-IgG peroxidase conjugate diluted 6,000 times and as a blocking agent 3% w/v skim milk in PBS. The titration of positive rabbit serum according to this procedure detected antibody concentrations up to 1:12,800 times. The present method, the conventional ELISA and passive haemagglutination assay are compared.

The new direct oral anticoagulants in special indications: rationale and preliminary data in cancer, mechanical heart valves, anti-phospholipid syndrome, and heparin-induced thrombocytopenia and beyond.

The present review will briefly summarize the interplay between coagulation and inflammation, highlighting possible effects of direct inhibition of factor Xa and thrombin beyond anticoagulation. Additionally, the rationale for the use of the new direct oral anticoagulants (DOACs) for indications such as cancer-associated venous thromboembolism (CAT), mechanical heart valves, thrombotic anti-phospholipid syndrome (APS), and heparin-induced thrombocytopenia (HIT) will be explored. Published data on patients with cancer or mechanical heart valves treated with DOAC will be discussed, as well as planned studies in APS and HIT. Although at the present time published evidence is insufficient for recommending DOAC in the above-mentioned indications, there are good arguments in favor of clinical trials investigating their efficacy in these contexts. Direct inhibition of factor Xa or thrombin may reveal interesting effects beyond anticoagulation as well.

Direct Determination of mechanical properties in shallow formations by (ultra) sonic methods

For several decades mechanical properties of shallow formations (soil) obtained by sonic to ultrasonic wave testing were reported to be greater than those based on mechanical tests. The present article relying on a statistical analysis of more than 300 tests shows that elastic moduli of the soil can indeed be obtained from (ultra)sonic tests and that they are identical to those resulting from mechanical tests.

Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism.

OBJECTIVE: This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). DESIGN: Cross-sectional study. PATIENTS AND METHODS: 74 men (19-74 years, mean 51·4 ± 1·4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. RESULTS: 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4·2 ± 0·3 nm, P < 0·0001). T levels remained suppressed at 120 min compared with baseline (13·7 ± 0·6 vs 16·5 ± 0·7 nm, P < 0·0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9·7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0·0001). CONCLUSIONS: Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state.

Let-7a Is a Direct EWS-FLI-1 Target Implicated in Ewing's Sarcoma Development.

Ewing's sarcoma family tumors (ESFT) are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA) expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC) and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

Human mercury exposure associated with small-scale gold mining in Burkina Faso.

PURPOSE: In Burkina Faso, gold ore is one of the main sources of income for an important part of the active population. Artisan gold miners use mercury in the extraction, a toxic metal whose human health risks are well known. The aim of the present study was to assess mercury exposure as well as to understand the exposure determinants of gold miners in Burkinabe small-scale mines.METHODS: The examined gold miners' population on the different selected gold mining sites was composed by persons who were directly and indirectly related to gold mining activities. But measurement of urinary mercury was performed on workers most susceptible to be exposed to mercury. Thus, occupational exposure to mercury was evaluated among ninety-three workers belonging to eight different gold mining sites spread in six regions of Burkina Faso. Among others, work-related exposure determinants were taken into account for each person during urine sampling as for example amalgamating or heating mercury. All participants were medically examined by a local medical team in order to identify possible symptoms related to the toxic effect of mercury.RESULTS: Mercury levels were high, showing that 69% of the measurements exceeded the ACGIH (American Conference of Industrial Hygienists) biological exposure indice (BEI) of 35 µg per g of creatinine (µg/g-Cr) (prior to shift) while 16% even exceeded 350 µg/g-Cr. Basically, unspecific but also specific symptoms related to mercury toxicity could be underlined among the persons who were directly related to gold mining activities. Only one-third among the studied subpopulation reported about less than three symptoms possibly associated to mercury exposure and nearly half of them suffered from at least five of these symptoms. Ore washers were more involved in the direct handling of mercury while gold dealers in the final gold recovery activities. These differences may explain the overexposure observed in gold dealers and indicate that the refining process is the major source of exposure.CONCLUSIONS: This study attests that mercury exposure still is an issue of concern. North-South collaborations should encourage knowledge exchange between developing and developed countries, for a cleaner artisanal gold mining process and thus for reducing human health and environmental hazards due to mercury use.