17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

The 17β-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P=0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P=0.0047). ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P=0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish

Divergence in Sex Steroid Hormone Signaling between Sympatric Species of Japanese Threespine Stickleback

Sex steroids mediate the expression of sexually dimorphic or sex-specific traits that are important both for mate choice within species and for behavioral isolation between species. We investigated divergence in sex steroid signaling between two sympatric species of threespine stickleback (Gasterosteus aculeatus): the Japan Sea form and the Pacific Ocean form. These sympatric forms diverge in both male display traits and female mate choice behaviors, which together contribute to asymmetric behavioral isolation in sympatry. Here, we found that plasma levels of testosterone and 17β-estradiol differed between spawning females of the two sympatric forms. Transcript levels of follicle-stimulating hormone-β (FSHβ) gene were also higher in the pituitary gland of spawning Japan Sea females than in the pituitary gland of spawning Pacific Ocean females. By contrast, none of the sex steroids examined were significantly different between nesting males of the two forms. However, combining the plasma sex steroid data with testis transcriptome data suggested that the efficiency of the conversion of testosterone into 11-ketotestosterone has likely diverged between forms. Within forms, plasma testosterone levels in males were significantly correlated with male body size, a trait important for female mate choice in the two sympatric species. These results demonstrate that substantial divergence in sex steroid signaling can occur between incipient sympatric species. We suggest that investigation of the genetic and ecological mechanisms underlying divergence in hormonal signaling between incipient sympatric species will provide a better understanding of the mechanisms of speciation in animals

Foxf2: A Novel Locus for Anterior Segment Dysgenesis Adjacent to the Foxc1 Gene

Anterior segment dysgenesis (ASD) is characterised by an abnormal migration of neural crest cells or an aberrant differentiation of the mesenchymal cells during the formation of the eye's anterior segment. These abnormalities result in multiple tissue defects affecting the iris, cornea and drainage structures of the iridocorneal angle including the ciliary body, trabecular meshwork and Schlemm's canal. In some cases, abnormal ASD development leads to glaucoma, which is usually associated with increased intraocular pressure. Haploinsufficiency through mutation or chromosomal deletion of the human FOXC1 transcription factor gene or duplications of the 6p25 region is associated with a spectrum of ocular abnormalities including ASD. However, mapping data and phenotype analysis of human deletions suggests that an additional locus for this condition may be present in the same chromosomal region as FOXC1. DHPLC screening of ENU mutagenised mouse archival tissue revealed five novel mouse Foxf2 mutations. Re-derivation of one of these (the Foxf2W174R mouse lineage) resulted in heterozygote mice that exhibited thinning of the iris stroma, hyperplasia of the trabecular meshwork, small or absent Schlemm's canal and a reduction in the iridocorneal angle. Homozygous E18.5 mice showed absence of ciliary body projections, demonstrating a critical role for Foxf2 in the developing eye. These data provide evidence that the Foxf2 gene, separated from Foxc1 by less than 70 kb of genomic sequence (250 kb in human DNA), may explain human abnormalities in some cases of ASD where FOXC1 has been excluded genetically

Work productivity in rhinitis using cell phones:The MASK pilot study

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI: AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P <0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI: AS (Rho=0.53, P <0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptom

Scots pine susceptibility to attack by Tomicus piniperda (L) as related to pruning date and attack density

The susceptibility of young Scots pine to bark beetle attack was increased by pruning trees to a similar crown size = 10, 7 and 1 month(s) prior to beetle flight. Beetle population in the study area was high, and spontaneous attacks were expected to occur on the pruned trees. Half of the trees were baited with split pine bolts in order to attract more beetles to attack these trees. Thus, experimental trees carrying = one-third of their original foliage and with different vigour indices due to the pruning history were exposed to 2 levels of beetle attack. The pine shoot beetles preferentially attacked baited trees, whereas attack rates did not differ between pruning dates. Six wk after attack, beetle performance was better in trees pruned shortly before attack than in trees pruned earlier. Vigour indices differed between the 2 treatments, but phloem starch, secondary resinosis (expressed as lesion size and resin acid content) and tree survival did not. Trees that eventually survived were significantly less attacked than those that died. but the 2 groups did not differ in tree characteristics (except in cambial electrical resistance).Susceptibilité du pin sylvestre aux attaques de Tomicus piniperda L en fonction de la date d'élagage et de la densité d'attaque. La susceptibilité de jeunes pins sylvestre aux attaques de scolytides a été accrue en élagant les arbres, de façon à ce que la taille de leur couronne soit comparable. Les élagages ont eu lieu environ 10, 7 et 1 mois avant le vol des insectes. Les niveaux de population dans la zone d'étude étaient élevés et des attaques spontanées étaient prévisibles sur les arbres élagués. Pour augmenter leur attractivité, la moitié des arbres ont été appâtés avec des rondins de pin. Ainsi, des arbres portant environ un tiers de leur feuillage d'origine, et ayant différents indices de vigueur à cause de l'élagage (tableau 1) ont été soumis à 2 niveaux d'attaque. La moitié des arbres ont été coupés début juin, les autres fin août. T piniperda a attaqué de préférence les arbres appâtés (figs 1, 2) mais le taux d'attaque a été le même pour les différentes dates d'élagage (fig 1). Six semaines après les attaques, les arbres élagués le plus tardivement renfermaient plus d'insectes parents et plus de galeries contenant des larves que les arbres élagués précocement (tableau II). Les galeries maternelles étaient aussi significativement plus longues dans le premier cas (fig 1). Les arbres élagués environ 1 an avant l'attaque représentaient donc un matériel moins favorable pour les insectes. Les indices de vigueur différaient également entre les 2 traitements (tableau I), mais l'amidon présent dans le liber, la réaction secondaire (mesurée par la taille de la zone réactionnelle et son contenu en acides résiniques) et le taux de survie des arbres étaient semblables (fig 1, tableau III). La réaction de défense induite a avorté sur certains des arbres qui supportait une densité d'attaque supérieure à 200 galeries maternelles par m2 (fig 3). La longueur moyenne des galeries dépassait 40 mm (fig 4). Cependant, des arbres plus densément attaqués ont survécu. Chez les arbres résistants, les lésions occupaient au maximum 30% de la surface du phloème dans la partie basse du tronc (fig 5). Les arbres supposés survivants étaient significativement moins attaqués que les morts, mais leur taille, leur croissance et leur indice de vigueur étaient les mêmes (tableau IV). Cependant, la résistance électrique du cambium mesurée à la date de l'attaque était significativement différente dans les 2 groupes, ce qui paraît illogique (tableau IV). Une descendance a été observée uniquement sur les arbres tués, avec un taux de multiplication inférieur à l'unité (tableau IV). Un début d'occlusion de l'aubier a été remarqué sur quelques arbres (potentiellement mourants ?) après 6 sem. L'aubier des arbres morts était fortement bleui, mais pas celui des arbres survivants