Age differences in biological monitoring of chemical exposure: a tentative description using a toxicokinetic model

AIM: Specific factors responsible for interindividual variability should be identified and their contribution quantified to improve the usefulness of biological monitoring. Among others, age is an easily identifiable determinant, which could play an important impact on biological variability. MATERIALS AND METHODS: A compartmental toxicokinetic model developed in previous studies for a series of metallic and organic compounds was applied to the description of age differences. Young male physiological and metabolic parameters, based on Reference Man information, were taken from preceding studies and were modified to take into account age based on available information about age differences. RESULTS: Numerical simulation using the kinetic model with the modified parameters indicates in some cases important differences due to age. The expected changes are mostly of the order of 10-20%, but differences up to 50% were observed in some cases. CONCLUSION: These differences appear to depend on the chemical and on the biological entity considered. Further work should be done to improve our estimates of these parameters, by considering for example uncertainty and variability in these parameters. [Authors]

Policy -Strategy Option Description, January 30, 2009

Like many states, Iowa faces significant challenges on the energy front.  Energy prices have  surged in recent years to record levels before declining precipitously following the financial  crisis that broke in September 2008.  Despite this pullback, the fundamentals that contributed to  higher energy prices are expected to return once economies rebound. Oil prices have gone up  on increased demand, driven in large part by developing countries such as China and India,  whose economies have been rapidly expanding.  Natural gas prices have also fluctuated  dramatically, trading in a range from $4.50 to $13.00/MMBtu over the past year, but are unlikely  to remain at low levels over the long term.  As shown in our analysis later on in this report, the  difference in levelized cost of electricity from a gas‐fired combined cycle plant can vary  significantly depending on the fuel cost.    Dependence on others for energy supply involves significant risks and uncertainties.  Thus, if  Iowa wishes to reduce its dependence on others – or even achieve energy independence – Iowa  needs to pursue actions on a numbers of fronts.  Following the status quo is not an option.    A carbon tax would change the energy landscape in Iowa.  Since Iowa is currently 75%  dependent on coal, a carbon tax could mean that generators, and in turn ratepayers, could be on  the hook for higher electricity prices, though it remains to be seen exactly what the tax scheme  will be.  In addition to existing plants, a carbon tax would also have a significant impact on the  cost of new generation plant.  We have modeled carbon taxes ranging from $0‐50/ton in our  analysis in the Appendix.  However, if a more aggressive carbon policy came into play resulting  in market values of for example, $100/ton or even $200/ton, then that could raise the cost of coal‐  and gas‐fired generation significantly, making alternatives such as wind more economical.

Maladies inflammatoires cryptogéniques de l'intestin de novo après transplantation hépatique: rapport de quatre nouveaux cas et revue de la littérature [De novo inflammatory bowel diseases after liver transplantation: description of four new cases and a review of the literature]

Inflammatory bowel diseases are a result of an aberrant mucosal immune response to gut microflora. Several groups have reported newly diagnosed inflammatory bowel diseases following solid organ transplantation and subsequent immunosuppressive therapy. We describe four cases of newly diagnosed inflammatory bowel diseases following liver transplantation in a pool of 120 transplanted patients. These patients had no prior history of inflammatory bowel diseases or primary sclerosing cholangitis and were immunosuppressed. Two patients were transplanted for a hepatitis C related cirrhosis, one for alcoholic cirrhosis and one patient for autoimmune cirrhosis. Three patients were diagnosed with ulcerative colitis and one with Crohn's disease. These four patients were on a cyclosporin monotherapy when their inflammatory bowel diseases were diagnosed. These data suggest that cyclosporin monotherapy following solid organ transplantation does not prevent development of inflammatory bowel diseases.

Molecular identification and characterization of the Arabidopsis delta(3,5),delta(2,4)-dienoyl-coenzyme A isomerase, a peroxisomal enzyme participating in the beta-oxidation cycle of unsaturated fatty acids.

Degradation of unsaturated fatty acids through the peroxisomal beta-oxidation pathway requires the participation of auxiliary enzymes in addition to the enzymes of the core beta-oxidation cycle. The auxiliary enzyme delta(3,5),delta(2,4)-dienoyl-coenzyme A (CoA) isomerase has been well studied in yeast (Saccharomyces cerevisiae) and mammals, but no plant homolog had been identified and characterized at the biochemical or molecular level. A candidate gene (At5g43280) was identified in Arabidopsis (Arabidopsis thaliana) encoding a protein showing homology to the rat (Rattus norvegicus) delta(3,5),delta(2,4)-dienoyl-CoA isomerase, and possessing an enoyl-CoA hydratase/isomerase fingerprint as well as aspartic and glutamic residues shown to be important for catalytic activity of the mammalian enzyme. The protein, named AtDCI1, contains a peroxisome targeting sequence at the C terminus, and fusion of a fluorescent protein to AtDCI1 directed the chimeric protein to the peroxisome in onion (Allium cepa) cells. AtDCI1 expressed in Escherichia coli was shown to have delta(3,5),delta(2,4)-dienoyl-CoA isomerase activity in vitro. Furthermore, using the synthesis of polyhydroxyalkanoate in yeast peroxisomes as an analytical tool to study the beta-oxidation cycle, expression of AtDCI1 was shown to complement the yeast mutant deficient in the delta(3,5),delta(2,4)-dienoyl-CoA isomerase, thus showing that AtDCI1 is also appropriately targeted to the peroxisome in yeast and has delta(3,5),delta(2,4)-dienoyl-CoA isomerase activity in vivo. The AtDCI1 gene is expressed constitutively in several tissues, but expression is particularly induced during seed germination. Proteins showing high homology with AtDCI1 are found in gymnosperms as well as angiosperms belonging to the Monocotyledon or Dicotyledon classes.

Marine and transitional Middle/Upper Eocenen units of the Southeastern Pyrenean Foreland Basin (NE Spain)

The stratigraphic basis of this work has allowed the use of larger foraminifers in the biostratigraphic characterisation of the new Shallow Benthic Zones (SBZ). This part of the volume presents a description of the sedimentary cycles formed by the transgressive-regressive systems of the Lutetian and Bartonian in the southeastern sector of the Ebro Foreland Basin. Concerning the Lutetian deposits studied in the Amer-Vic and Empordà areas, four sedimentary cycles have been characterised. The first and second are found within the Tavertet/Girona Limestone Formation (Reguant, 1967; Pallí, 1972), while the third and fourth cycles cover the Coll de Malla Marl Formation (Clavell et al., 1970), the Bracons Formation (Gich, 1969, 1972), the Banyoles Marl Formation (Almela and Ríos, 1943), and the Bellmunt Formation (Gich, 1969, 1972). In the Bartonian deposits studied in the Igualada area, two transgressive-regressive sedimentary cycles have been characterised in the Collbàs Formation (Ferrer, 1971), the Igualada Formation (Ferrer, 1971), and the Tossa Formation (Ferrer, 1971). The Shallow Benthic Zones (SBZs) recognised within the Lutetian are the following: SBZ 13, from the Early Lutetian, in the transgressive system of the first cycle; SBZ 14, from the Middle Lutetian, in the second cycle and the lower part of the transgressive system of the third cycle; SBZ 15, from the Middle Lutetian, in the remaining parts of the third system; SBZ 16, from the Late Lutetian, throughout the fourth cycle. The association of larger foraminifers in the first and second cycles of the Bartonian in the Igualada area has been used as the basis for the definition of SBZs 17 and 18 recognised in the Bartonian of the western Tethys.

Small RNA-dependent expression of secondary metabolism is controlled by Krebs cycle function in Pseudomonas fluorescens.

Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the rhizosphere of crop plants, elaborates and excretes several secondary metabolites with antibiotic properties. Their synthesis depends on three small RNAs (RsmX, RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two-component system at high cell population densities. To find regulatory links between primary and secondary metabolism in P. fluorescens and in the related species Pseudomonas aeruginosa, we searched for null mutations that affected central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp reporter constructs but without slowing down the growth rate in rich media. Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase isoenzyme) resulted in up-regulation of the three small RNAs and secondary metabolism in the absence of detectable nutrient limitation. These effects required the GacS sensor kinase but not the accessory sensors RetS and LadS. An analysis of intracellular metabolites in P. fluorescens revealed a strong positive correlation between small RNA expression and the pools of 2-oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates (already known to control GacA-dependent virulence factors in P. aeruginosa) exert a critical trigger function in secondary metabolism via the expression of GacA-dependent small RNAs.

Serum antimüllerian hormone levels remain stable through the menstrual cycle and after oral or vaginal administration of synthetic sex steroids

Rapport de synthèse : Objectif de l'étude : étudier si l'administration orale ou vaginale d'hormones contraceptives influence les concentrations sériques d'hormone antimüllérienne (AMH). Design : essai prospectif chez des femmes recrutées par annonce. Les femmes désireuses d'avoir une contraception ont été randomisées entre une contraception orale et une contraception vaginale. Celles qui ne souhaitaient pas de contraception ont été incluses dans le groupe témoin. Cadre de l'étude : unité de médecine de la reproduction d'un hôpital universitaire. Patientes : vingt-quatre jeunes femmes en bonne santé avec des cycles menstruels réguliers qui n'avaient pas utilisé de contraception hormonale pendant les trois mois précédant l'étude. Intervention : contraception orale ou vaginale du 5ème au 25ème jour du cycle menstruel dans les groupes contraception versus pas de contraception dans le groupe témoin. Mesure d'issue : variations inter et intra-cycle des concentrations sériques d'AMH dans les trois groupes: groupe témoin en cycle spontané et groupes sous contraception oestroprogestative orale ou vaginale. Résultats : les fluctuations d'AMH observées pendant le cycle menstruel (variations intra-cycle) restent dans les valeurs des variations entre deux cycles (variations inter-cycles) tant chez les femmes en cycle spontané que chez les femmes sous contraception orale ou vaginale. Conclusions : nos résultats confirment que les concentrations sériques d'AMH restent stables pendant le cycle menstruel et indiquent qu'elles ne sont pas influencées par l'administration exogène de stéroïdes sexuels contraceptifs, que ce soit par voie orale ou vaginale.

Preliminary description and slope stability analyses of the 2008 Little Salmon lake and 2007 Mt. Steele landslides, Yukon

In August 2008, reactivation of the Little Salmon Lake landslide occurred. During this event, hundreds of conical mounds of variable size and composition formed in the deposition zone. The characteristics of these landforms are described and a potential mechanism for their formation is proposed. A preliminary slope stability analysis of the 2007 Mount Steele rock and ice avalanche was also undertaken. The orientation of very high persistence (>20 m long) structural planes (e.g., faults, joints and bedding) within bedrock in the source zone was obtained using an airborne-LiDAR digital elevation model and the software COLTOP-3D. Using these discontinuity orientation measurements, kinematic, surface wedge and simple three-dimensional distinct element slope stability analyses were performed.