Role of androgen and gonadotrophins in the development and function of the Sertoli cells and Leydig cells: data from mutant and genetically modified mice

Development and maintenance of the male phenotype and establishment of fertility are all dependent upon the activity of the Sertoli cells and Leydig cells of the testis. This review examines the regulation and function of these cell during fetal and post-natal development. Fetal Leydig cells are sensitive to both luteinising hormone (LH) and adrenocorticotrophic hormone (ACTH) but Leydig cell function appears normal in fetal mice lacking both hormones or their receptors. Post-natally, the Sertoli cells and Leydig cells are reliant upon the pituitary gonadotrophins. Leydig cells are critically dependent on LH but follicle-stimulating hormone (FSH), presumably acting through the Sertoli cell, can also affect Leydig cell function. Testosterone secreted by the Leydig cells acts with FSH to stimulate Sertoli cell activity and spermatogenesis. Study of animals lacking FSH-receptors and androgen-receptors shows that both hormones can act to maintain the meiotic germ cell population but that androgens are critical for completion of meiosis

Effect of FSH on testicular morphology and spermatogenesis in gonadotrophin-deficient hypogonadal mice lacking androgen receptors

Follicle stimulating hormone (FSH) and androgen act to stimulate and maintain spermatogenesis. FSH acts directly on the Sertoli cells to stimulate germ cell number and acts indirectly to increase androgen production by the Leydig cells. In order to differentiate between the direct effects of FSH on spermatogenesis and those mediated indirectly through androgen action we have crossed hypogonadal (hpg) mice which lack gonadotrophins with mice lacking androgen receptors (AR) either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with recombinant FSH for 7 days and testicular morphology and cell numbers assessed. In untreated hpg and hpg.SCARKO mice germ cell development was limited and did not progress beyond the pachytene stage. In hpg.ARKO mice testes were smaller with fewer Sertoli cells and germ cells compared to hpg mice. Treatment with FSH had no effect on Sertoli cell number but significantly increased germ cell numbers in all groups. In hpg mice FSH increased numbers of spermatogonia and spermatocytes and induced round spermatid formation. In hpg.SCARKO and hpg.ARKO mice, in contrast, only spermatogonial and spermatocyte numbers were increased with no formation of spermatids. Leydig cell numbers were increased by FSH in hpg and hpg.SCARKO mice but not in hpg.ARKO mice. Results show that in rodents 1) FSH acts to stimulate spermatogenesis through an increase in spermatogonial number and subsequent entry of these cells into meiosis, 2) FSH has no direct effect on the completion of meiosis and 3) FSH effects on Leydig cell number are mediated through interstitial ARs

Pattern formation in directional solidification under shear flow. I: Linear stability analysis and basic patterns

An asymptotic interface equation for directional solidification near the absolute stabiliy limit is extended by a nonlocal term describing a shear flow parallel to the interface. In the long-wave limit considered, the flow acts destabilizing on a planar interface. Moreover, linear stability analysis suggests that the morphology diagram is modified by the flow near the onset of the Mullins-Sekerka instability. Via numerical analysis, the bifurcation structure of the system is shown to change. Besides the known hexagonal cells, structures consisting of stripes arise. Due to its symmetry-breaking properties, the flow term induces a lateral drift of the whole pattern, once the instability has become active. The drift velocity is measured numerically and described analytically in the framework of a linear analysis. At large flow strength, the linear description breaks down, which is accompanied by a transition to flow-dominated morphologies, described in a companion paper. Small and intermediate flows lead to increased order in the lattice structure of the pattern, facilitating the elimination of defects. Locally oscillating structures appear closer to the instability threshold with flow than without.Comment: 20 pages, Latex, accepted for Physical Review

Exploring flavor structure of supersymmetry breaking from rare B decays and unitarity triangle

We study effects of supersymmetric particles in various rare B decay processes as well as in the unitarity triangle analysis. We consider three different supersymmetric models, the minimal supergravity, SU(5) SUSY GUT with right-handed neutrinos, and the minimal supersymmetric standard model with U(2) flavor symmetry. In the SU(5) SUSY GUT with right-handed neutrinos, we consider two cases of the mass matrix of the right-handed neutrinos. We calculate direct and mixing-induced CP asymmetries in the b to s gamma decay and CP asymmetry in B_d to phi K_S as well as the B_s--anti-B_s mixing amplitude for the unitarity triangle analysis in these models. We show that large deviations are possible for the SU(5) SUSY GUT and the U(2) model. The pattern and correlations of deviations from the standard model will be useful to discriminate the different SUSY models in future B experiments.Comment: revtex4, 36 pages, 10 figure

Iodine Intake is Associated with Thyroid Function in Mild to Moderately Iodine Deficient Pregnant Women

Background: Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied. The aim of this study was to investigate the association between iodine intake and thyroid function during pregnancy. Design: In a population-based pregnancy cohort including 2910 pregnant women participating in The Norwegian Mother and Child Cohort Study, we explored cross sectional associations of maternal iodine intake measured (1) by a food frequency questionnaire and (2) as iodine concentration in a spot urine sample, with plasma thyroid hormones and antibodies. Results: Biological samples were collected in mean gestational week 18.5 (standard deviation 1.3) and diet was assessed in gestational week 22. Median iodine intake from food was 121 μg/day (interquartile range 90, 160), and 40% reported use of iodine-containing supplements in pregnancy. Median urinary iodine concentration (UIC) was 59 μg/L among those who did not use supplements and 98 μg/L in the women reporting current use at the time of sampling, indicating mild to moderate iodine deficiency in both groups. Iodine intake as measured by the food frequency questionnaire was not associated with the outcome measures, while UIC was inversely associated with FT3 (p = 0.002) and FT4 (p < 0.001). Introduction of an iodine-containing supplement after gestational week 12 was associated with indications of lower thyroid hormone production (lower FT4, p = 0.027, and nonsignificantly lower FT3, p = 0.17). The 2.5th and 97.5th percentiles of TSH, FT4, and FT3 were not significantly different by groups defined by calculated iodine intake or by UIC. Conclusion: The results indicate that mild to moderate iodine deficiency affect thyroid function in pregnancy. However, the differences were small, suggesting that normal reference ranges can be determined based on data also from mildly iodine deficient populations, but this needs to be further studied. Introducing an iodine-containing supplement might temporarily inhibit thyroid hormone production and/or release

Modelling thirty-day mortality in the acute respiratory distress syndrome (ARDS) in an adult ICU

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsVariables predicting thirty-day outcome from Acute Respiratory Distress Syndrome (ARDS) were analysed using Cox regression structured for time-varying covariates. Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral chest X-ray opacities, PaO₂/FiO₂ ratio of <200 and an acute precipitating event) were identified using a prospective computerized data base in a university teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8); ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO₂/FiO₂ ratio was 92 (31), 81% had four-quadrant chest X-ray opacification and lung injury score was 2.75 (0.45). Average mechanical ventilator tidal volume was 10.3 ml/ predicted kg weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus indirect injury, 2.89 (1.45-5.76); PaO₂/FiO₂ ratio, 0.98 (0.97-0.99); operative versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were evident for PaO₂/FiO₂ ratio, operative versus non-operative category and ventilator tidal volume assessed as a categorical predictor with a cut-point of 8 ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg predicted weight). Thirty-day survival was improved for patients ventilated with lower tidal volumes. Survival predictors in ARDS were multifactorial and related to patient-injury-time interaction and level of mechanical ventilator tidal volume.J. L. Moran, P. J. Solomon, V. Fox, M. Salagaras, P. J. Williams, K. Quinlan, A. D. Berstenhttp://www.aaic.net.au/Article.asp?D=200332

A modular analysis of the Auxin signalling network

Auxin is essential for plant development from embryogenesis onwards. Auxin acts in large part through regulation of transcription. The proteins acting in the signalling pathway regulating transcription downstream of auxin have been identified as well as the interactions between these proteins, thus identifying the topology of this network implicating 54 Auxin Response Factor (ARF) and Aux/IAA (IAA) transcriptional regulators. Here, we study the auxin signalling pathway by means of mathematical modeling at the single cell level. We proceed analytically, by considering the role played by five functional modules into which the auxin pathway can be decomposed: the sequestration of ARF by IAA, the transcriptional repression by IAA, the dimer formation amongst ARFs and IAAs, the feedback loop on IAA and the auxin induced degradation of IAA proteins. Focusing on these modules allows assessing their function within the dynamics of auxin signalling. One key outcome of this analysis is that there are both specific and overlapping functions between all the major modules of the signaling pathway. This suggests a combinatorial function of the modules in optimizing the speed and amplitude of auxin-induced transcription. Our work allows identifying potential functions for homo- and hetero-dimerization of transcriptional regulators, with ARF:IAA, IAA:IAA and ARF:ARF dimerization respectively controlling the amplitude, speed and sensitivity of the response and a synergistic effect of the interaction of IAA with transcriptional repressors on these characteristics of the signaling pathway. Finally, we also suggest experiments which might allow disentangling the structure of the auxin signaling pathway and analysing further its function in plants

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR