Organizing Effects of Sex Steroids on Brain Aromatase Activity in Quail

Preoptic/hypothalamic aromatase activity (AA) is sexually differentiated in birds and mammals but the mechanisms controlling this sex difference remain unclear. We determined here (1) brain sites where AA is sexually differentiated and (2) whether this sex difference results from organizing effects of estrogens during ontogeny or activating effects of testosterone in adulthood. In the first experiment we measured AA in brain regions micropunched in adult male and female Japanese quail utilizing the novel strategy of basing the microdissections on the distribution of aromatase-immunoreactive cells. The largest sex difference was found in the medial bed nucleus of the stria terminalis (mBST) followed by the medial preoptic nucleus (POM) and the tuberal hypothalamic region. A second experiment tested the effect of embryonic treatments known to sex-reverse male copulatory behavior (i.e., estradiol benzoate [EB] or the aromatase inhibitor, Vorozole) on brain AA in gonadectomized adult males and females chronically treated as adults with testosterone. Embryonic EB demasculinized male copulatory behavior, while vorozole blocked demasculinization of behavior in females as previously demonstrated in birds. Interestingly, these treatments did not affect a measure of appetitive sexual behavior. In parallel, embryonic vorozole increased, while EB decreased AA in pooled POM and mBST, but the same effect was observed in both sexes. Together, these data indicate that the early action of estrogens demasculinizes AA. However, this organizational action of estrogens on AA does not explain the behavioral sex difference in copulatory behavior since AA is similar in testosterone-treated males and females that were or were not exposed to embryonic treatments with estrogens

Unintentional asphyxia, SIDS, and medically explained deaths:A descriptive study of outcomes of child death review (CDR) investigations following sudden unexpected death in infancy

Background: A comprehensive Child Death Review (CDR) program was introduced in England and Wales in 2008 but as yet data have only been analysed at a local level, limiting the learning from deaths. The aim of this study is to describe the profile of causes and risk factors for Sudden Unexpected Death in Infancy (SUDI) as determined by the new CDR program. Methods: This was a descriptive outcome study using data from Child Death Overview Panel (CDOP) Form C for SUDI cases dying during 2010-2 in the West Midlands region of England. The main outcome measures were: cause of death, risk factors and potential preventability of death, and determination of deaths probably due to unintentional asphyxia. Results: Data were obtained for 65/70 (93%) SUDI cases. 20/65 (31%) deaths were initially categorised as due to medical causes; 21/65 (32%) as SIDS, and 24/65 (37%) as undetermined. Reanalysis suggested that 2/21 SIDS and 7/24 undetermined deaths were probably due to unintentional asphyxia, with 6 of these involving co-sleeping and excessive parental alcohol consumption. Deaths classified as ‘undetermined’ had significantly higher total family and environmental risk factor scores (mean 2.6, 95% CI 2.0– 3.3) compared to those classified as SIDS (mean 1.6, 95% CI 1.2-1.9), or medical causes for death (mean 1.1, 95% CI 0.8-1.3). 9/20 (47%) of medical deaths, 19/21 (90%) SIDS and 23/24 (96%) undetermined deaths were considered to be potentially preventable. There were inadequacies in medical provision identified in 5/20 (25%) of medically explained deaths. Conclusions: The CDR program results in detailed information about risk factors for SUDI cases but failed to recognise deaths probably due to unintentional asphyxia. The misclassification of probable unintentional asphyxial deaths and SIDS as ‘undetermined deaths’ is likely to limit learning from these deaths and inhibit prevention strategies. Many SUDI occurred in families with mental illness, substance misuse and chaotic lifestyles and most in unsafe sleep-environments. This knowledge could be used to better target safe sleep advice for vulnerable families and prevent SUDI in the future

An evaluation of gender equity in different models of primary care practices in Ontario

Background: The World Health Organization calls for more work evaluating the effect of health care reforms on gender equity in developed countries. We performed this evaluation in Ontario, Canada where primary care models resulting from reforms co-exist. // Methods: This cross sectional study of primary care practices uses data collected in 2005-2006. Healthcare service models included in the study consist of fee for service (FFS) based, salaried, and capitation based. We compared the quality of care delivered to women and men in practices of each model. We performed multi-level, multivariate regressions adjusting for patient socio-demographic and economic factors to evaluate vertical equity, and adjusting for these and health factors in evaluating horizontal equity. We measured seven dimensions of health service delivery (e.g. accessibility and continuity) and three dimensions of quality of care using patient surveys (n = 5,361) and chart abstractions (n = 4,108). // Results: Health service delivery measures were comparable in women and men, with differences ≤ 2.2% in all seven dimensions and in all models. Significant gender differences in the health promotion subjects addressed were observed. Female specific preventive manoeuvres were more likely to be performed than other preventive care. Men attending FFS practices were more likely to receive influenza immunization than women (Adjusted odds ratio: 1.75, 95% confidence intervals (CI) 1.05, 2.92). There was no difference in the other three prevention indicators. FFS practices were also more likely to provide recommended care for chronic diseases to men than women (Adjusted difference of -11.2%, CI -21.7, -0.8). A similar trend was observed in Community Health Centers (CHC). // Conclusions: The observed differences in the type of health promotion subjects discussed are likely an appropriate response to the differential healthcare needs between genders. Chronic disease care is non equitable in FFS but not in capitation based models. We recommend that efforts to monitor and address gender based differences in the delivery of chronic disease management in primary care be pursued.Funding for the original study on which this research is based was provided by the Ontario Ministry of Health and Long Term Care Primary Health Care Transition Fund. The views expressed in this report are the views of the authors and do not necessarily reflect those of the Ontario Ministry of Health and Long Term Care

Inter-Relationship between Testicular Dysgenesis and Leydig Cell Function in the Masculinization Programming Window in the Rat

The testicular dysgenesis syndrome (TDS) hypothesis proposes that maldevelopment of the testis, irrespective of cause, leads to malfunction of the somatic (Leydig, Sertoli) cells and consequent downstream TDS disorders. Studies in rats exposed in utero to di(n-butyl) phthalate (DBP) have strongly supported the TDS concept, but so far no direct evidence has been produced that links dysgenesis per se to somatic cell dysfunction, in particular to androgen production/action during the ‘masculinization programming window’ (MPW; e15.5–e18.5). Normal reproductive tract development and anogenital distance (AGD) are programmed within the MPW, and TDS disorders arise because of deficiencies in this programming. However, DBP-induced focal testicular dysgenesis (Leydig cell aggregation, ectopic Sertoli cells, malformed seminiferous cords) is not evident until after the MPW. Therefore, we used AGD as a read-out of androgen exposure in the MPW, and investigated if this measure was related to objectively quantified dysgenesis (Leydig cell aggregation) at e21.5 in male fetuses exposed to vehicle, DBP (500 or 750 mg/kg/day) or the synthetic glucocorticoid dexamethasone (Dex; alone or plus DBP-500) from e15.5–e18.5 (MPW), e13.5–e20.5 or e19.5–e20.5 (late window). Dysgenesis was found only in animals exposed to DBP during the MPW, and was negatively correlated (R2 = −0.5) with AGD at e21.5 and at postnatal day 8, irrespective of treatment period. Dysgenesis was also negatively correlated (R2 = –0.5) with intratesticular testosterone (ITT) at e21.5, but only when treatments in short windows (MPW, late window) were excluded; the same was true for correlation between AGD and ITT. We conclude that AGD, reflecting Leydig cell function solely within the MPW, is strongly related to focal dysgenesis. Our results point to this occurring because of a common early mechanism, targeted by DBP that determines both dysgenesis and early (during the MPW) fetal Leydig cell dysfunction. The findings provide strong validation of the TDS hypothesis

Digital Gene Expression Profiling by 5′-End Sequencing of cDNAs during Reprogramming in the Moss Physcomitrella patens

Stem cells self-renew and repeatedly produce differentiated cells during development and growth. The differentiated cells can be converted into stem cells in some metazoans and land plants with appropriate treatments. After leaves of the moss Physcomitrella patens are excised, leaf cells reenter the cell cycle and commence tip growth, which is characteristic of stem cells called chloronema apical cells. To understand the underlying molecular mechanisms, a digital gene expression profiling method using mRNA 5′-end tags (5′-DGE) was established. The 5′-DGE method produced reproducible data with a dynamic range of four orders that correlated well with qRT-PCR measurements. After the excision of leaves, the expression levels of 11% of the transcripts changed significantly within 6 h. Genes involved in stress responses and proteolysis were induced and those involved in metabolism, including photosynthesis, were reduced. The later processes of reprogramming involved photosynthesis recovery and higher macromolecule biosynthesis, including of RNA and proteins. Auxin and cytokinin signaling pathways, which are activated during stem cell formation via callus in flowering plants, are also activated during reprogramming in P. patens, although no exogenous phytohormone is applied in the moss system, suggesting that an intrinsic phytohormone regulatory system may be used in the moss

Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa

Lujo virus (LUJV), a new member of the family Arenaviridae and the first hemorrhagic fever–associated arenavirus from the Old World discovered in three decades, was isolated in South Africa during an outbreak of human disease characterized by nosocomial transmission and an unprecedented high case fatality rate of 80% (4/5 cases). Unbiased pyrosequencing of RNA extracts from serum and tissues of outbreak victims enabled identification and detailed phylogenetic characterization within 72 hours of sample receipt. Full genome analyses of LUJV showed it to be unique and branching off the ancestral node of the Old World arenaviruses. The virus G1 glycoprotein sequence was highly diverse and almost equidistant from that of other Old World and New World arenaviruses, consistent with a potential distinctive receptor tropism. LUJV is a novel, genetically distinct, highly pathogenic arenavirus

A combined functional and structural genomics approach identified an EST-SSR marker with complete linkage to the Ligon lintless-2 genetic locus in cotton (Gossypium hirsutum L.)

<p>Abstract</p> <p>Background</p> <p>Cotton fiber length is an important quality attribute to the textile industry and longer fibers can be more efficiently spun into yarns to produce superior fabrics. There is typically a negative correlation between yield and fiber quality traits such as length. An understanding of the regulatory mechanisms controlling fiber length can potentially provide a valuable tool for cotton breeders to improve fiber length while maintaining high yields. The cotton (<it>Gossypium hirsutum </it>L.) fiber mutation Ligon lintless-2 is controlled by a single dominant gene (<it>Li₂</it>) that results in significantly shorter fibers than a wild-type. In a near-isogenic state with a wild-type cotton line, <it>Li₂</it>is a model system with which to study fiber elongation.</p> <p>Results</p> <p>Two near-isogenic lines of Ligon lintless-2 (<it>Li₂</it>) cotton, one mutant and one wild-type, were developed through five generations of backcrosses (BC₅). An F₂population was developed from a cross between the two <it>Li₂</it>near-isogenic lines and used to develop a linkage map of the <it>Li₂</it>locus on chromosome 18. Five simple sequence repeat (SSR) markers were closely mapped around the <it>Li₂</it>locus region with two of the markers flanking the <it>Li₂</it>locus at 0.87 and 0.52 centimorgan. No apparent differences in fiber initiation and early fiber elongation were observed between the mutant ovules and the wild-type ones. Gene expression profiling using microarrays suggested roles of reactive oxygen species (ROS) homeostasis and cytokinin regulation in the <it>Li₂</it>mutant phenotype. Microarray gene expression data led to successful identification of an EST-SSR marker (NAU3991) that displayed complete linkage to the <it>Li₂</it>locus.</p> <p>Conclusions</p> <p>In the field of cotton genomics, we report the first successful conversion of gene expression data into an SSR marker that is associated with a genomic region harboring a gene responsible for a fiber trait. The EST-derived SSR marker NAU3991 displayed complete linkage to the <it>Li₂</it>locus on chromosome 18 and resided in a gene with similarity to a putative plectin-related protein. The complete linkage suggests that this expressed sequence may be the <it>Li₂</it>gene.</p