Sexual selection in seaweed? Testing Bateman's principles in the red alga Gracilaria gracilis.

In anisogamous species, sexual selection is expected to be stronger in males. Bateman's principles state that the variance in (i) reproductive and (ii) mating success is greater for males, and (iii) the relationship between reproductive success and mating success (the Bateman gradient) is also stronger for males than for females. Sexual selection, based on Bateman's principles, has been demonstrated in animals and some angiosperms, but never in a seaweed. Here we focus on the oogamous haploid-diploid rhodophyte Gracilaria gracilis in which previous studies have shown evidence for non-random mating, suggesting the existence of male-male competition and female choice. We estimated mating and reproductive success using paternity analyses in a natural population where up to 92% of fertilizations occurred between partners of that population. The results show that the variance in mating success is significantly greater in males than in females and that the Bateman gradient is positive only in males. Distance to female partners also explains a minor part of the variance in male mating success. Although there is no evidence for sexual dimorphism, our study supports the hypothesis that sexual selection occurs in G. gracilis, probably on male traits, even if we cannot observe, characterize or quantify them yet.

Pollinators of the sea: A discovery of animal-mediated fertilization in seaweed.

The long-held belief that animal-mediated pollination is absent in the sea has recently been contradicted in seagrasses, motivating investigations of other marine phyla. This is particularly relevant in red algae, in which female gametes are not liberated and male gametes are not flagellated. Using experiments with the isopod Idotea balthica and the red alga Gracilaria gracilis, we demonstrate that biotic interactions dramatically increase the fertilization success of the alga through animal transport of spermatia on their body. This discovery suggests that animal-mediated fertilization could have evolved independently in terrestrial and marine environments and raises the possibility of its emergence in the sea before plants moved ashore.

MANOTA: a promising bifunctional chelating agent for copper-64 immunoPET.

Improved bifunctional chelating agents (BFC) are required for copper-64 radiolabelling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific imaging agents. Four different bifunctional chelating agents (BFC) were evaluated for Fab (Fragment antigen binding) conjugation and radiolabelling with copper-64. Two DOTA- (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and two NOTA- (1,4,7-triazacyclononane-1,4,7-triacetic acid) derivatives bearing a p-benzyl-isothiocyanate group were conjugated to Fab-trastuzumab - which targets the HER2/neu receptor - and the average number of chelators attached ranged from 2.4 to 4.3 macrocycles per Fab. Labelling of the immunoconjugate with copper-64 was achieved in high radiochemical yields after 45 min at 37 °C, and the radiochemical purity of each 64Cu-BFC-Fab-trastuzumab reached 97% after purification. The affinity of each 64Cu-BFC-Fab-trastuzumab ranged between 10 and 50 nM as evaluated by in vitro saturation assays using the HCC1954 breast cancer cell line. PET-MR imaging and biodistribution studies were performed in mice bearing breast cancer BT-474 xenografts. BT-474 tumours were clearly visualized on PET images at 4 and 24 hours post-injection. The tumour uptake of 64Cu-BFC-Fab-trastuzumab reached 8.9 to 12.8% ID g-1 24 hours post-injection and significant differences in non-specific liver uptake were observed depending on the BFC conjugated, the lowest being observed with MANOTA. These results show that MANOTA is a valuable tool for copper-64 radiolabelling.

[Audit "Toys and incubators in neonatology"]. / Audit << Les jouets et les couveuses en néonatologie >>

Owing to an increase in nosocomial septicaemias in the Neonatalogy department, we've judged it necessary to consider the role of items not linked to the nursing procedures, and nevertheless present in the incubators, as well as the hygiene techniques applied to them. In November 2007, we've made a longitudinal prospective study consisting in an observation audit during 3 successive days, observing every single incubator with a newborn baby. In each incubator, we've checked whether there were or not items that weren't required by the nursing activities, along with their characteristics and the hygiene procedures applied to them. We've inquired as well whether the parents and the nursing staff knew and applied the required hygiene procedures. In 13 among the 17 incubators under survey, at least one item not strictly required by the nursing procedures could be found. The number of toys in each incubator varied from seven to one. Among the 33 toys surveyed, 24 (73%) of them showed a score of maximum fluffiness (4 out of 4), and only 10 wore labels giving cleansing advice from the manufacturers. Without any record about the cleaning/disinfecting of the toys brought in hospital, we have observed that the parents were given varied advice about how to clean the toys at home before putting them in the incubators (only four parents had washed the toys in their washing machines at more than 30 degrees C). From the six samples under scrutiny, all the culture results were tested positive. In particular two of the soft toys sampled were found infected by a Pseudomonas oryzihabitans. These particular toys belonged to a baby who had been diagnosed with a septicaemia characterized by hemocultures positive to a P. oryzihabitans of a different strain. Our audit has been an efficient reminder that any item put in an incubator is a potential vector and reservoir of pathogen organisms. After a general feedback towards the department staff, the medical staff then prescribed to permanently ban all the items not strictly required by the nursing activities from all the incubators of the department.

[Lidocaine intoxication in newborn following maternal pudendal anesthesia: report of three cases]. / Intoxication néonatale à la lidocaïne après analgésie par bloc des nerfs honteux: à propos de trois observations.

Pudendal nerve block may be indicated during instrumental delivery in situations where peridural anesthesia is unavailable. We report three cases of neonatal lidocaine intoxication following maternal pudendal block during delivery. Clinical features were hypotonia, pupillary mydriasis fixed to light, apnea, cyanosis and seizures. Two neonates required mechanical ventilation. Lidocaine was found in the serum of two babies. In all three cases, recovery was complete. The pharmacokinetics of lidocaine in a highly vascularized perineum during labor increase the risk of neonatal intoxication. A possible intoxication by local anesthetics should be considered in neonates presenting an acute distress in the delivery room.

PERMANENT GENETIC RESOURCES: Isolation of microsatellite loci from the kelp, Saccorhiza polyschides (Heterokontophyta, incertae sedis).

Kelps are ecologically important seaweeds that dominate the subtidal zones of rocky coasts. In Northern Europe, Saccorhiza polyschides is a pioneer species suspected of outcompeting the harvested kelp, Laminaria digitata. To examine how the process of species competition affects species distribution and genetic diversity in coastal environments, we developed 10 polymorphic microsatellite markers for S. polyschides using an enriched library (microsatellites are already available for L. digitata). These loci showed from three to 24 alleles with heterozygosities ranging from 0.36 to 0.92. This polymorphism is high enough for fine-scale population analyses including assignment tests to determine the origin of recruits.

Arsenic trioxide and acute promyelocytic leukemia: clinical and biological.

Arsenic has recently been identified as an effective drug in the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. Indeed, arsenic trioxide combined with all-trans retinoic acid shows a synergistic effect. Mechanistically, arsenic targets the key leukemogenic protein PML-RARalpha, setting up a new example of molecular target-based cancer therapy.

Past and current gene flow in the selfing, wind-dispersed species Mycelis muralis in western Europe.

The distribution of genetic diversity in Mycelis muralis, or wall lettuce, was investigated at a European scale using 12 microsatellite markers to infer historical and contemporary forces from genetic patterns. Mycelis muralis has the potential for long-distance seed dispersal by wind, is mainly self-pollinated, and has patchily distributed populations, some of which may show metapopulation dynamics. A total of 359 individuals were sampled from 17 populations located in three regions, designated southern Europe (Spain and France), the Netherlands, and Sweden. At this within-region scale, contemporary evolutionary forces (selfing and metapopulation dynamics) are responsible for high differentiation between populations (0.34 < F(ST) < 0.60) but, contrary to expectation, levels of within-population diversity, estimated by Nei's unbiased expected heterozygosity (H(E)) (0.24 < H(E) < 0.68) or analyses of molecular variance (50% of the variation found within-populations), were not low. We suggest that the latter results, which are unusual in selfing species, arise from efficient seed dispersal that counteracts population turnover and thus maintains genetic diversity within populations. At the European scale, northern regions showed lower allelic richness (A = 2.38) than populations from southern Europe (A = 3.34). In light of postglacial colonization hypotheses, these results suggest that rare alleles may have been lost during recolonization northwards. Our results further suggest that mutation has contributed to genetic differentiation between southern and northern Europe, and that Sweden may have been colonized by dispersers originating from at least two different refugia.

Sampling and analysis of carbon in diesel exhaust particulates--an international comparison.

OBJECTIVES: The European Co-ordination on Diesel Soot Exposure (ECDSE) working group organised a laboratory inter-comparison which integrated both the sampling and the analytical determination. The aim was to gain more information on the performance of the methods for the determination of diesel particulate matter at workplaces and on their comparability, and to also confirm that the requirements of the European standard EN 482 are fulfilled for this analytical procedure. METHODS: Sampling was carried out in a diesel aerosol test chamber where participants used their own sampling devices. Overall, ten sampling exercises at two different concentration levels were performed and both personal air sampling systems and stationary samplers were used. The analytical determination was performed according to the laboratory's own standard procedure. RESULTS: There was good agreement between the laboratories for the determination of organic carbon (OC), elemental carbon (EC) and total carbon (TC). Almost all the results when expressed as a coefficient of variation were in the range +/-30% of the overall means. The results also showed that the coefficient of variation for OC was approximately twice the coefficient of variation for EC. This is not too critical, because existing occupational exposure levels (OELs) are based on the measurement of EC. CONCLUSIONS: The inter-comparison showed that existing analytical procedures for the determination of diesel particulate matter at workplaces fulfil the requirements of European standard EN 482. Both personal air samplers and stationary samplers give comparable results. The parameters for the analytical determination are not critical within the range of parameter values presented in this article. Additionally, it may be concluded that the diesel aerosol test chamber used in this exercise is well suited for producing an atmosphere containing a constant and reproducible level of diesel particulate matter.

Exposure to carcinogenic polycyclic aromatic compounds and health risk assessment for diesel-exhaust exposed workers.

OBJECTIVES: Workers' exposure to diesel exhaust in a bus depot, a truck repair workshop and an underground tunnel was determined by the measuring of elemental carbon (EC) and 15 carcinogenic polycyclic aromatic compounds (PACs) proposed by the US Department of Health and Human Services/National Toxicology Program (NTP). Based on these concentration data, the genotoxic PAC contribution to the diesel-exhaust particle (DEP) lung-cancer risk was calculated. METHOD: Respirable particulate matter was collected during the summer and winter of 2001 (except for in the underground situation) and analysed by coulometry for EC and by GC-MS methods for PACs. The use of potency equivalence factors (PEFs) allowed the studied PAC concentrations to be expressed as benzo[a]pyrene equivalents (B[a]P(eq)). We then calculated the lung-cancer risk due to PACs and DEPs by multiplying the B[a]P(eq) and EC concentrations by the corresponding unit risk factor. The ratio of these two risks values has been considered as an estimate of the genotoxic contribution to the DEP cancer risk. RESULTS: For the bus depot and truck repair workshop, exposure to EC and PACs has been shown to increase by three to six times and ten times, respectively, during winter compared to summer. This increase has been attributed mainly to a decrease in ventilation during the cold. With the PEF approach, the B[a]P(eq) concentration is five-times higher than if only benzo[ a]pyrene (B[a]P) is considered. Dibenzopyrenes contribute an important part to this increase. A simple calculation based on unit risk factors indicates that the studied PAC contribution to the total lung-cancer risk attributed to DEPs is in the range of 3-13%. CONCLUSIONS: The 15 NTP PACs represent a small but non-negligible part of lung-cancer risk with regard to diesel exposure. From this point of view, the dibenzopyrene family are important compounds to be considered.

[Bidirectional cell traffic between mother and fetus: new insights in pediatric and adult disorders]. / Trafic bidirectionnel de cellules entre mère et foetus: un éclairage nouveau dans les pathologies de l'adulte et de l'enfant.

There is a heavy traffic of cells and DNA through the placenta during pregnancy. The rate of fetal cells in the maternal blood is correlated with abnormalities, such as aneuploidy and pre-eclampsia. Studying and quantifying these cells could improve antenatal diagnosis techniques, especially for Down syndrome. Maternal-fetal microchimerism is frequently observed in several auto-immune diseases in adulthood, such as systemic scleroderma. Studies suggest a rather allo-immune pathophysiology, involving maternal-fetal HLA compatibility. Microchimerism is also found in auto-immune diseases in children. Thus, the cells traffic offers new insights for antenatal diagnosis techniques and pathophysiology of auto-immune diseases.

Further round-robin tests to improve the comparability between laboratories of the measurement of carbon in diesel soot and in environmental samples.

OBJECTIVES: An informal European coordination group organized two round-robin tests on filters collected from environmental, workplace and diluted diesel emissions. Previous inter-laboratory comparisons have shown that experimental samples give reasonably good results in terms of the dispersion around the mean, from all the participating laboratories. However, there were significant differences between the laboratories owing to a narrow distribution of the results within a single laboratory. In order to gain a better understanding of the differences obtained between the laboratories, it was decided to carry out more round-robin tests and to investigate further the possible factors which may influence the results. METHODS: The first round-robin (RRT3) was performed on six different samples (eight replicates) analyzed by ten laboratories. The range of loading was 40 to 138 micrograms cm-2 of total carbon (TC). Laboratories used their own thermal procedure parameters. The second round-robin test (RRT4) was performed on three different diluted diesel emissions (two replicates) samples analyzed by 13 laboratories. The range of loading was 21 to 37 micrograms cm-2 TC. Laboratories analyzed samples using imposed temperatures (500, 650 and 800 degrees C) and imposed duration (12 min). RESULTS: Inter-laboratory coefficients of variation for diluted diesel emission samples were 10% for RRT3 and ranged from 6 to 19% for RRT4. The influence of the desorption temperature was clearly demonstrated and the results tended to show that a desorption temperature of 650 degrees C could be an acceptable compromise. The influence of the organic carbon/elemental carbon (OC/EC) ratio was shown to be insignificant with pure diesel soot samples. CONCLUSIONS: It was expected that a significant improvement would be seen in the inter-laboratory dispersion by the use of a common standardized thermal desorption program, but the objectives of these RRTs were only partly reached. This paper provides new information that will be useful in the elaboration of a standardized procedure for the European Normalisation Centre (CEN TC 137 WG2--General requirements for measuring procedures).

BCL-2 cooperates with promyelocytic leukemia retinoic acid receptor alpha chimeric protein (PMLRARalpha) to block neutrophil differentiation and initiate acute leukemia.

The promyelocytic leukemia retinoic acid receptor alpha (PMLRARalpha) chimeric protein is associated with acute promyelocytic leukemia (APL). PMLRARalpha transgenic mice develop leukemia only after several months, suggesting that PMLRARalpha does not by itself confer a fully malignant phenotype. Suppression of apoptosis can have a central role in tumorigenesis; therefore, we assessed whether BCL-2 influenced the ability of PMLRARalpha to initiate leukemia. Evaluation of preleukemic animals showed that whereas PMLRARalpha alone modestly altered neutrophil maturation, the combination of PMLRARalpha and BCL-2 caused a marked accumulation of immature myeloid cells in bone marrow. Leukemias developed more rapidly in mice coexpressing PMLRARalpha and BCL-2 than in mice expressing PMLRARalpha alone, and all mice expressing both transgenes succumbed to leukemia by 7 mo. Although both preleukemic, doubly transgenic mice and leukemic animals had abundant promyelocytes in the bone marrow, only leukemic mice exhibited thrombocytopenia and dissemination of immature cells. Recurrent gain of chromosomes 7, 8, 10, and 15 and recurrent loss of chromosome 2 were identified in the leukemias. These chromosomal changes may be responsible for the suppression of normal hematopoiesis and dissemination characteristic of the acute leukemias. Our results indicate that genetic changes that inhibit apoptosis can cooperate with PMLRARalpha to initiate APL.

Isolation and characterization of an equine foamy virus.

Foamy viruses (FVs) are complex retroviruses which have been isolated from different animal species including nonhuman primates, cattle, and cats. Here, we report the isolation and characterization of a new FV isolated from blood samples of horses. Similar to other FVs, the equine foamy virus (EFV) exhibits a highly characteristic ultrastructure and induces syncytium formation and subsequent cell lysis on a large number of cell lines. Molecular cloning of EFV reveals that the general organization is that of other known FVs, whereas sequence similarity with its bovine FV counterpart is only 40%. Interestingly, EFV buds exclusively from the plasma membrane and not from the endoplasmic reticulum (ER), as previously shown for other FVs. The absence of the ER retrieval dilysine motif in EFV Env is likely responsible for this unexpected sorting pathway.

Switzerland: the status of silicosis from the past to the end of the 20th century. Control and prevention.

The silicosis issue in Switzerland is reviewed on the basis of data provided by Suva, the Swiss National Insurance Fund, in charge of law enforcement and of prevention. Pictures of the past period and nowadays consecutively to the occupational medicine surveillance and industrial hygiene practice showed that major improvements have been realized. In the 30's, a constant rise of new cases of silicosis has been observed every year. From 1940 to end of the 60's, a plateau was reached with about 200 to 300 cases per year. Since 1974, a significant decrease is observed, the annual number of new cases being about 100. Since 1989, the new cases level off at 30-50 per year due to drastic control measures and present announced cases are residuals of previous exposures. The number of annual deaths ranges at the unit level with a patient's life expectancy nearly equal to that of the general population. Prevention efforts however should be continued since the activities of concern have changed. Small enterprises with a limited number of personnel dispersed throughout the country, working in the sectors of stone cutting and grinding, civil engineering and cleaning of building surfaces make prevention difficult and may lower its efficiency. In addition, information should also reach categories of individual workers like professional pottery crafstmen or leisure-exposed persons.

Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia.

In acute promyelocytic leukemia (APL) patients, retinoic acid (RA) triggers differentiation while arsenic trioxide (arsenic) induces both a partial differentiation and apoptosis. Although their mechanisms of action are believed to be distinct, these two drugs both induce the catabolism of the oncogenic promyelocytic leukemia (PML)/RARalpha fusion protein. While APL cell lines resistant to one agent are sensitive to the other, the benefit of combining RA and arsenic in cell culture is controversial, and thus far, no data are available in patients. Using syngenic grafts of leukemic blasts from PML/RARalpha transgenic mice as a model for APL, we demonstrate that arsenic induces apoptosis and modest differentiation, and prolongs mouse survival. Furthermore, combining arsenic with RA accelerates tumor regression through enhanced differentiation and apoptosis. Although RA or arsenic alone only prolongs survival two- to threefold, associating the two drugs leads to tumor clearance after a 9-mo relapse-free period. These studies establishing RA/arsenic synergy in vivo prompt the use of combined arsenic/RA treatments in APL patients and exemplify how mouse models of human leukemia can be used to design or optimize therapies.