Interplay of DNA supercoiling and catenation during the segregation of sister duplexes.

The discrete regulation of supercoiling, catenation and knotting by DNA topoisomerases is well documented both in vivo and in vitro, but the interplay between them is still poorly understood. Here we studied DNA catenanes of bacterial plasmids arising as a result of DNA replication in Escherichia coli cells whose topoisomerase IV activity was inhibited. We combined high-resolution two-dimensional agarose gel electrophoresis with numerical simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules. We showed that in those replication intermediates formed in vivo, catenation and negative supercoiling compete with each other. In interlinked molecules with high catenation numbers negative supercoiling is greatly limited. However, when interlinking decreases, as required for the segregation of newly replicated sister duplexes, their negative supercoiling increases. This observation indicates that negative supercoiling plays an active role during progressive decatenation of newly replicated DNA molecules in vivo.

The meaning of marriage for men during the transition to fatherhood : the Swiss context

In Europe, Switzerland presents an unusual pattern of marriage with a very high proportion of couples who begin to cohabit without being married, but with a very low proportion of nonmarital births. A lot of couples marry before the conception of the child or during the pregnancy. In this article we focus on the point of view of men vis-agrave-vis the marriage and its meanings. Qualitative investigations show that men strongly desire marriage for several reasons, from their desire to participate in child rearing to the fear of having their paternity denied by Swiss institutions

Determinants of maternal sex steroids during the first half of pregnancy.

OBJECTIVE: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2). METHODS: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. RESULTS: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus. CONCLUSION: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. LEVEL OF EVIDENCE: II.

An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major.

The possible immunomodulatory role of polymorphonuclear leukocytes (PMN) in CD4+ T lymphocyte differentiation in mice was examined by studying the effect of transient depletion of PMN during the early phase after Leishmania major delivery. A single injection of the PMN-depleting NIMP-R14 mAb 6 h before infection with L. major prevented the early burst of IL-4 mRNA transcription otherwise occurring in the draining lymph node of susceptible BALB/c mice. Since this early burst of IL-4 mRNA transcripts had previously been shown to instruct Th2 differentiation in mice from this strain, we examined the effect of PMN depletion on Th subset differentiation at later time points after infection. The transient depletion of PMN in BALB/c mice was sufficient to inhibit Th2 cell development otherwise occurring after L. major infection. Decreased Th2 responses were paralleled with partial resolution of the footpad lesions induced by L. major. Furthermore, draining lymph node-derived CD4+ T cells from PMN-depleted mice remained responsive to IL-12 after L. major infection, unlike those of infected BALB/c mice receiving control Ab. PMN depletion had no effect when the NIMP-R14 mAb was injected 24 h postinfection. The protective effect of PMN depletion was shown to be IL-12 dependent, as concomitant neutralization of IL-12 reversed the protective effect of PMN depletion. These results suggest a role for an early wave of PMN in the development of the Th2 response characteristic of mice susceptible to infection with L. major.

Effets du stress sur l'évolution des représentations parentales au cours des 12 premiers mois de vie d'un enfant né avec une fente faciale = Stress influence on parental representations' development during the first year of a child born with a facial cleft

La venue au monde d'un enfant avec une fente faciale constitue un événement stressant, voire traumatique, pour les parents. Que ce soit à travers le risque de symptômes associés, la logistique d'alimentation ou par simples raisons d'esthétisme, de nombreuses personnes vivent l'annonce de la présence d'une fente faciale comme une intrusion brutale dans le vécu de la grossesse et une interruption momentanée de l'investissement représentationnel du foetus. À travers notre recherche, nous montrons qu'un haut stress n'influe pas forcément négativement sur le développement de la relation entre le parent et l'enfant et que, au contraire, dans le cas des pères, il peut contribuer à l'implication émotionnelle envers le bébé. Le moment de l'annonce de la malformation a aussi une importance dans les représentations à propos de l'enfant puisque si elle est faite durant la période prénatale, elle permet aux parents un réarrangement des représentations afin de mieux accueillir le bébé le jour de sa naissance. The birth of a child with a facial cleft is often seen as a very stressing event for both parents. Risks of comorbidity, difficulty in nutrition or just aesthetical reasons are frequently invoked while describing this moment. The announcement of the deformation is felt like a brutal intrusion in representations associated to pregnancy. Then, we can observe a kind of disinvestment of the coming baby. Through our study, we find that high stress has not always a bad issue on relationship between parents and infants. In contrary, this kind of chronic stress can preserve the well-being of the relationship, especially for fatherhood. The time of facial deformation announcement also plays its part in representations about the baby. Before birth, it opens room for reordering and modifying representations, then the baby will be accepted as it should be on his birthday.

Severe hypertension following accidental clonidine overdose during the refilling of an implanted intrathecal drug delivery system.

BACKGROUND:   Complications associated with intrathecal pumps may be linked to the surgical procedure, the implanted device, or the medication itself.¦CASE REPORTS:   Three patients treated chronically with intrathecal clonidine presented with clonidine overdose due to inadvertent extravasation during the refilling procedure. All patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment.¦DISCUSSION:   Clonidine is an alpha-2 agonist with a nearly 100% bioavailability after oral or rectal administration. With high plasma concentration secondary to massive systemic overdose, the specificity for the alpha-2 receptor is lost and an alpha-1 agonist activity predominates and causes marked hypertension. Management of clonidine overdose consists of supportive therapy guided by signs and symptoms.¦CONCLUSION:   Inadvertent injection into the subcutaneous pocket rather than the reservoir is rare but very dangerous as the drug cannot be retrieved and massive doses are involved. Signs and symptoms of systemic overdose with drugs commonly used in implanted drugs delivery system should be well known to ensure early diagnosis and treatment.

Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women.

OBJECTIVE: To define the dynamics of antimüllerian hormone (AMH) and inhibins during the physiologic menstrual cycle. DESIGN: Longitudinal study. SETTING: University hospital. PATIENT(S): 36 young, healthy, normal weight Caucasian women without medication. INTERVENTION(S): Normal ovulatory menstrual cycles were evaluated by regular blood sampling taken every other day and periovulatory every day. MAIN OUTCOME MEASURE(S): Serum concentrations of AMH, inhibin A and B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, progesterone, and free testosterone were measured in all blood samples. RESULT(S): Median AMH levels are statistically significantly higher in the late follicular compared with ovulation or the early luteal phase. There are statistically significant correlations between both AMH and FSH, and AMH and free testosterone in all cycle phases. Inhibin A increases strongly in the late follicular phase and peaks at day LH + 4. Inhibin B shows a broad midfollicular and a sharp early luteal peak, the difference being statistically significant between day LH + 4 and the earlier time points and between day LH + 2 and day LH. Although there is a negative association between inhibin A or B and the body mass index (BMI), there is no correlation between AMH and the BMI. CONCLUSION(S): Levels of AMH show a statistically significant change during the menstrual cycle and may influence the circulating gonadotropin and steroid hormone levels.

Diffusion of influenza during the winter of 1889-90 in Switzerland

The influenza of the winter of 1889-90 was one of the first epidemics to spread all over the world. At the time, several people hypothesized that the railway was one of the main vectors of diffusion of this influenza. This hypothesis was defended in Switzerland especially by Schmid, Chief of the Swiss Office of Health, who collected an impressive body of material about the spread of the epidemic in that country. These data on influenza combined with data about the structure of the railway are used in this paper in order to test the hypothesis of a mixed diffusion process, first between communes interconnected by the railway, and secondly, between those communes and neighbouring communes. An event history analysis model taking into account diffusion effects is proposed and estimated. Results show that the hypothesis is supported if the railway network in Switzerland is not taken as a whole but if a distinction between railway companies is made.

Temporal variation in glucocorticoid levels during the resting phase is associated in opposite way with maternal and paternal melanic coloration.

Sex-dependent selection can help maintain sexual dimorphism. When the magnitude of selection exerted on a heritable sex trait differs between the sexes, it may prevent each sex to reach its phenotypic optimum. As a consequence, the benefit of expressing a sex trait to a given value may differ between males and females favouring sex-specific adaptations associated with different values of a sex trait. The level of metabolites regulated by genes that are under sex-dependent selection may therefore covary with the degree of ornamentation differently in the two sexes. We investigated this prediction in the barn owl, a species in which females display on average larger black spots on the plumage than males, a heritable ornament. This melanin-based colour trait is strongly selected in females and weakly counter-selected in males indicating sex-dependent selection. In nestling barn owls, we found that daily variation in baseline corticosterone levels, a key hormone that mediates life history trade-offs, covaries with spot diameter displayed by their biological parents. When their mother displayed larger spots, nestlings had lower corticosterone levels in the morning and higher levels in the evening, whereas the opposite pattern was found with the size of paternal spots. Our study suggests a link between daily regulation of glucocorticoids and sex-dependent selection exerted on sexually dimorphic melanin-based ornaments.

Pronostic à long terme des patients ayant bénéficié d'une thrombolyse au stade aigu de l'infarctus du myocarde [Long-term prognosis for patients undergoing thrombolysis during the acute phase of myocardial infarction]

OBJECTIVE: The objective of this study was to analyse the long-term mortality and morbidity of a group of patients undergoing thrombolysis during the acute phase of myocardial infarction and to determine the factors influencing the prognosis. One hundred and seventy five patients (149 mean and 26 women, mean age: 54 years) were included in a randomized study, comparing the efficacy of 2 thrombolytic substances administered during the acute phase of myocardial infarction. A standard questionnaire was sent to the various attending physicians to follow-up of these 175 patients. RESULTS: The hospital mortality was 5% (9 patients) and 14 patients (9%) died after a mean follow-up of 4.3 +/- 2.1 years. The 5-year actuarial survival was 81%. Fourteen patients (8%) were lost to follow-up and 49 patients (32%) underwent surgical or percutaneous revascularization during follow-up. Revascularized patients had a significantly better survival than non-revascularized patients. The mean left ventricular ejection fraction of patients who died was lower (48% versus 71%) than that of survivors. Patients with an ejection fraction < 40% also had a significantly lower survival (p = 0.01). Patency of the vessel after thrombolysis was associated with a slightly better survival; this difference was not significant. The ejection fraction at 6 month was also significantly higher (60 +/- 10% versus 49 +/- 11%) for patients with a patent artery. Three risk factors for death or reinfarction were identified: age > 65 years at the time of infarction, disease in more than one coronary vessel and absence of angina pectoris before infarction. The probability of a coronary accident varied from 2 to 88% according to the number of risk factors present. At the time of follow-up, 60% of patients presented hypercholesterolaemia versus only 7% before infarction 73% of patients received anticoagulant or antiaggregant treatment and 81% of patients were asymptomatic. CONCLUSION: The mortality and the acute and long-term morbidity of myocardial infarction remain high, as only 34% of our patients did not develop any events during follow-up, despite serious medical management and follow-up. The ejection fraction has an important prognostic value. Patient management should take the abovementioned risk factors into account.